UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Polydactyly in British Columbia, 1964-1967 Jones, Daryl Christine 1971

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Notice for Google Chrome users:
If you are having trouble viewing or searching the PDF with Google Chrome, please download it here instead.

Item Metadata

Download

Media
831-UBC_1971_A6_7 J65_4.pdf [ 11.98MB ]
Metadata
JSON: 831-1.0101922.json
JSON-LD: 831-1.0101922-ld.json
RDF/XML (Pretty): 831-1.0101922-rdf.xml
RDF/JSON: 831-1.0101922-rdf.json
Turtle: 831-1.0101922-turtle.txt
N-Triples: 831-1.0101922-rdf-ntriples.txt
Original Record: 831-1.0101922-source.json
Full Text
831-1.0101922-fulltext.txt
Citation
831-1.0101922.ris

Full Text

POLYDACTYLY IU BRITISH COLUMBIA 1964 - 1967 by DARYL CHRISTINE JONES B.Sc, Portland State University, 1969 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN GENETICS i n the Di v i s i o n of Medical Genetics We accept•this thesis as conforming to the required standard THE UNIVERSITY OP BRITISH COLUMBIA SEPTEMBER 1971 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. flopartmcirt of 7/lAs./s,&df, Mztclfce-/^ The University of British Columbia Vancouver 8, Canada. Date Jf fQf.U^ /IM i Abstract , The B r i t i s h Columbia [B.C.] Polydactyly study was designed to investigate the occurrence cf Polydactyly i n the B.C. population. Polydactylous infants born in the province i n the years 1964 - 1967 were ascertained principally through the Registry for Handicapped Children and Adults; additional cases were found-through disease indexes of B.- C. hospitals and through referrals from medical personnel. Data on the probands were obtained by family interviews and review of various medical records. Information compiled for a case included: sex of proband, racial background, parental age, parity of mother, notes on the preg-nancy, description of accessory digits, genetic family history, and nature of. additional congenital anomalies when rpresent. Incidence of Polydactyly i n B.C. for 1964 - 1967 was 1.02 per 1,000 live births. This figure includes patients with multiple congenital anomalies. Of the four years covered by the study, 1966 had the highest incidence (1.35), a year i n which a seemingly disproportionate number of ulnar cases occurred. Ninety-five males and 43 females, a sex ratio of approximately 2 : 1 , presented the following types of duplication: radial (31), t i b i a l (6), ulnar (54), fibular (24) and ulnar and fibular (16). It i s proposed that cases with both ulnar and fibular accessory digits and cases with ulnar or fibular accessory digits i n whose family both ulnar and fibular duplication occur present ulnar-fibular type Polydactyly. Based on cases unassociated with multiple congenital anomalies, specific types of Polydactyly had the following incidences: radial 0.20; t i b i a l , 0.04; polysyndactyly, 0.01; ulnar, 0.32; fibular, 0.16; and ulnar-fibular, 0.09. Genetic histories indicate i n 32 families out of 138 there is another i n -dividual with Polydactyly. For specific types of Polydactyly the following proportion of cases without multiple congenital anomalies had a positive family history: radial, 5 - 19 %; t i b i a l , 0 %; ulnar, 29 %• fibular, 25 and ulnar-fibular, 73 f°~ Polygenic inheritance of ulnar and of fibular types of Polydactyly is suggested by the finding that the percentage of affected sibs is greater when there is a history of Polydactyly i n previous generations (approximately 6.6 fo) than for probands with a negative history (1.2 fo). The number of affected sibs of the probands (3/107) is in agreement with the number which would be expected for a polygenic t r a i t . Data for ulnar-fibular Polydactyly is more compatible with dominant inheritance with reduced penetrance among females. F i f t y percent of the offspring of polydactylous males were affected; a smaller percentage of the children of affected mothers were polydactylous (27.7 Nonpenetrance of the Polydactyly gene(s) would seem to be f a i r l y common among females since unaffected mothers are known to pass the t r a i t to their children whereas such an occurrence is unknown for males. . Among ulnar-fibular cases with no history of accessory digits i n previous generations, 17.4 % of the sibs were polydactylous. Major congenital anomaly was noted i n 33 probands and occurs approximately 3-5- times more frequently among the polydactylous infants than the general pop-ulation. Multiple major anomalies are approximately 25 times more frequent. A polydactylous child found to have one major malformation is twice as l i k e l y to have additional major anomalies than a child with one major anomaly who has the normal number of digits. Multiple congenital anomalies were most commonly seen with ulnar-fibular Polydactyly. This may reflect the fact that ulnar-fibular duplication is the type most commonly seen as a feature of various syndromes. In addition to the B.C. findings, literature on Polydactyly has been reviewed. Included are: data on the incidence of Polydactyly i n other popu-lations, description of different types of duplication, hypotheses regarding the inheritance of accessory digits, tabulation of the types of Polydactyly seen i n various syndromes, and discussion of the morphogenesis of accessory digits i n relation to limb embryogenesis. i i i Contents I. Introduction 1 A. Purpose of study 1 B. Embryology 2 I I . Methods 9 A. Ascertainment 9 B. Follow-up 11 C. Incidence 13 D. Racial background of probands 13 E. Parental age 14 P. B i r t h order of the probands 15 G. Extent of duplication 15 H. Genetic family history 16 I. Multiple congenital anomalies 16 I I I . Geographical D i s t r i b u t i o n 18 A. Results and discussion 18 IV. Incidence 21 A. Literature review 21 B. Incidence i n B r i t i s h Columbia by year, 1964-1967 24 C. Incidence i n B r i t i s h Columbia by month 27 D. Incidence and r a c i a l o r i g i n 27 E. Incidence by sex 30 V. Parental Age and Pa r i t y 33 A. Results and discussion 33 VI. Forms of Polydactyly 38 A. Introduction 38 B. Thumb Polydactyly 40 C. Triphalangeal f i r s t d i g i t s 43 i v Contents D. T i b i a l Polydactyly 46 E. Polydactyly of the index finger 46 P. Polydactyly of the t h i r d or fourth fingers 48 G. Ulnar Polydactyly 49 H. Fibular Polydactyly 50 I. Ulnar-fibularrpolydactyly 53 J. Polysyndactyly 54 K. Results 54 L. Discussion 61 VII. Genetics 66 A. Introduction 66 B. Literature review 67 C. Genetic family h i s t o r i e s : results 72 D. Genetic family h i s t o r i e s : discussion 76 E. Penetrance: results and discussion 78 F. Conclusions and speculation ' 83 V I I I . Multiple Congenital Anomalies 87 A. Introduction 87 B. Results 88 Minor anomalies 88 Single major anomalies 90 Multiple major anomalies 92 C. Discussion 94 D. Syndromes 99 Down's syndrome 99 Trisomy 17-18 syndrome 104 Trisomy D. syndrome 106 Contents Cyclopia 110 Polydactyly/imperforate anus/vertebral anomalies syndrome 11 3 Laurence-Moon-Biedl syndrome 118 Smith-Lemli-Opitz syndrome 1 20 P o l y c y s t i c kidneys, i n t e r n a l hydrocephalus and p o s t a x i a l Polydactyly syndrome 121 IX. Summary 124 X. L i t e r a t u r e Cited 126 XI. Appendix A - 1 4 3 A. Guide to data regarding the probands and key to abbreviations and symbols 143 B. Case descriptions 146 XII. Appendix B: Dermatoglyphics 192 XIII. Appendix C . 1 9 9 A. References f o r cases with trisomy E (17-18) syndrome 199 B. References f o r cases with trisomy syndrome 203 D. References f o r cases with polydactyly/imperforate anus/vertebral anomalies syndrome and cases with s i m i l a r anomalies 207 v i Tables I. Sources of Ascertainment and Information 10 I I . Geographical D i s t r i b u t i o n of Probands by Birthplace 19 I I I . Incidence of Polydactyly i n Different Races 22 IV. Incidence of Polydactyly i n B r i t i s h Columbia, 1964 - 1967 25 V. Number of Cases of Specific Types of Polydactyly i n 1964 - 1967 26 VI. Incidence of Polydactyly i n B r i t i s h Columbia by Month 28 VII. Incidence of Polydactyly among Males and Females i n B r i t i s h Columbia, 1964 - 1967 31 VI I I . Mean Parental Age at the B i r t h of the Probands 34 IX. Mean Parental Age at the B i r t h of Male and of Female Probands 35 X. B i r t h Order of the Probands and of Live Births i n B r i t i s h Columbia, 1964-1967 37 XI. Hand Affected i n Cases with Radial Polydactyly 42 XII. Frequency of Accessory Digit s i n Conjunction with T i b i a l Polydactyly 47 XI I I . Frequency of Accessory D i g i t s i n Conjunction with Ulnar Polydactyly 51 XIV. Site of Duplication According to Sex of the Probands 55 XV. Description of the Forms of Duplication Presented by the Probands 58 XVI. Incidence of Specific Types of Polydactyly i n B r i t i s h Columbia 62 XVII. Types of Polydactyly Found i n Singapore 63 XVIII. Cases with a Positive Family History of. Polydactyly 74 XIX. Penetrance of Postaxial Polydactyly 79 XX. Proportion of Polydactylous Offspring i n Families with Two or More Affected Individuals .82 XXI. Type of Polydactyly Presented by Children with a Minor Anomaly 89 v i i Tables XXII. Type of Polydactyly Presented by Children with One Major Anomaly 91 XXIII. Type of Polydactyly Presented by Children with Multiple Major Anomalies 93 XXIV. Type of Polydactyly Associated with Additional Congenital Anomalies 98 XXV. Syndromes and Anomaly Complexes Associated with Duplicated D i g i t s ' 1 0 0 XXVI. Cardinal Features of the Newborn with Down's Syndrome 103 XXVII. C l i n i c a l Features of Trisomy 17-18 Syndrome 105 XXVIII. C l i n i c a l Features of Trisomy D1 Syndrome 108 XXIX. Si t e of Polydactyly i n Trisomy !)• Syndrome 109 XXXX. Cases of Polydactyly Associated with Cyclopia 112 XXXI. C l i n i c a l Features of the Polydactyly/imperforate Anus/ Vertebral Anomalies Syndrome 115 XXXII. D i g i t a l Anomalies of the Polydactyly/imperforate Anus/ Vertebral Anomalies Syndrome 11 6 XXXIII. C l i n i c a l Features of the Laurence-Moon-Biedl Syndrome 119 XXXIV. C l i n i c a l Features of the Smith-Lemli-Opitz Syndrome 122 XXXV. D i g i t a l Anomalies of the Smith-Lemli-Opitz Syndrome 123 v i i i Figures and Plates Figure 1. Map of the Province of B r i t i s h Columbia 20 Plate Dermatoglyphics of Ulnar Polydactyly, Postminimi 177 Plate 2. Dermatoglyphics of Ulnar Polydactyly, Well-formed, A r t i c u l a t i o n D i g i t s 178 Plate 3. Dermatoglyphics of Fibular Polydactyly 179 Plate 4. Dermatoglyphics of Radial Polydactyly 180 Plate 5. Dermatoglyphics of Polysyndactyly 181 i x Acknowledgments The author g r a t e f u l l y acknowledges the continued support and di r e c t i o n of her committee chairman Dr. J . R. M i l l e r , Head of the Div i s i o n of Medical Genetics, and committee members Dr. R. B. Dowry and Dr. C. W. Roberts. Miss A. E. Scott, Administrator of the Registry for Handicapped Children and Adults, and her s t a f f provided invaluable assistance. To i n d i v i d u a l l y thank the many people of the Pro v i n c i a l Health Units, the Department of. Indian A f f a i r s , and the B. C. hospitals and physicians who assisted i n gathering the data i s not possible but th e i r cooperation i s greatly appreciated. The author i s p a r t i c u l a r l y grateful f o r the warm cooperation of the pa r t i c i p a t i n g families who were essential to the success of this study and for the kind assistance of many individuals who made the f i e l d work so enjoyable. Of special assistance i n preparing the thesis were Miss S. M. Manning, who drew out the pedigrees, Mr. D. Guthrie, who photographed the plates, and T. K., who helped with the typing. This work was supported by a grant from the Vancouver Foundation. 1 I. Introduction Polydactyly, the abnormal duplication of a d i g i t or d i g i t s , i s a hetero-geneous anomaly occurring both on the postaxial part of the hands or feet,; adjacent to the fourth or f i f t h d i g i t s , and on the preaxial part, adjacent to the f i r s t or second d i g i t s . Expression ranges from a complete, functional extra finger or toe to a small skin tag or polysyndactylous duplication of a d i s t a l phalanx. Duplication occurs as an isolated entity, i n association with other d i g i t a l anomalies.such as syndactyly, and as part of a number of multiple congenital anomaly complexes, some of which are recognized syndromes. Many polydactylous individuals with postaxial duplication have a family history of accessory d i g i t s whereas f a m i l i a l inheritance i s uncommon among preaxial cases. A strong genetic component i n the etiology of Polydactyly has been postulated. A. Purpose of study Despite the tremendous volume of l i t e r a t u r e on Polydactyly, data available have been inadequate to answer many basic questions: (a) What i s the incidence of s p e c i f i c forms of Polydactyly among newborns i n a given population? (b) What i s the sex r a t i o among individuals with a s p e c i f i c form of Poly-dactyly? (c) What percentage of infants with a s p e c i f i c form of Polydactyly have a positive family history for the same or a different type of Polydactyly? (d) Do data on families with two or more polydactylous individuals support the theory that postaxial accessory d i g i t s of types A and B (Sverdrup, 1922; see section VII, p.70) are genetically d i s t i n c t ? (e) How commonly i s the gene (genes) for Polydactyly apparently nonpenetrant among males and among females? 2 (f) In man does parental age and/or p a r i t y appear to be a f a c t o r i n the occurrence of accessory d i g i t s ? (g) Is there an increased frequency of major or minor anomalies among i n d i -viduals with a s p e c i f i c type of Polydactyly? (h) Do polydactylous i n d i v i d u a l s with multiple congenital anomalies, some of which present recognized syndromes, commonly have a p o s i t i v e family h i s t o r y of Polydactyly? The B r i t i s h Columbia [B.C.]] Polydactyly study on which t h i s d i s s e r t a t i o n i s based was designed to gather information which could be used to answer these and a d d i t i o n a l questions. B. Embryology P r e c i s e l y what tri g g e r s the development of polydactylous limbs and how t h e i r embryopathy proceeds i n man i s l a r g e l y unknown. Papers by Streeter (1930, 1942, 1945, 1948, 1949, 1951) and by Nishimura and colleagues, as well as the chapter on embryology by Barsky (1958), are p a r t i c u l a r l y valuable i n charting limb morphogenesis i n man. Porelimb buds, appear opposite the f i f t h to seventh c e r v i c a l somites around the 26th - 28th day of gestation at Horizon 12 (s t r e e t e r , 1942) or morphological age 4 (Nishimura & Yamamura, 1969); hindlimb buds appear somewhat l a t e r , at Horizon 13 or morphological age 5-Considerable v a r i a t i o n i n the extent of development among embryos of presumably the same chronological age has been noted (Nishimura & Yamamura, 1969). As the small ridges of tiss u e comprising the limb buds extend d i s t a l l y , there i s d i f f e r e n t i a t i o n of a proximal region which w i l l form the upper part of the limb and a d i s t a l region from which the hand or foot i s derived. A f l a t t e n i n g of the dorsal end of the upper limb buds which represents the hand occurs around the f i f t h week (Horizon 16-17, morphological age 8). Morpho-genesis of the hands proceeds somewhat i n advance of the feet, which i s 3 compatible with the observation from thalidomide embryopathy that duplication of the thumbs may res u l t from maternal ingestion of thalidomide around day 34 - 38 whereas duplication of the f i r s t toes results from ingestion around day 41 - 44 (Lenz, 1964). The anlagen of the fingers become v i s i b l e i n the s i x t h week as s l i g h t elevations on the dorsal surface of the hand plate (Horizon 17-18, morphological age 9). Towards the end of the s i x t h week the limbs project nearly straight forward, a l l i n t e r d i g i t a l notches are present i n the periphery of the hand plate, and anlagen of the d i g i t a l rays become v i s i b l e i n the feet (Horizon 18-19, morphological age 10). At t h i s time an i r r e g u l a r i t y i n the number of developing d i g i t s may be distinguished. This i s i l l u s t r a t e d i n the 1966 paper of Wishimura et al.: One plate shows the poly-dactylous hands of an embryo of Horizon 18 i n which there i s an excessive amount of tissue p r e a x i a l l y on both limbs marked by a supernumerary i n t e r -d i g i t a l notch. The photograph suggests development of the l e f t hand i s slightOy advanced r e l a t i v e to the r i g h t , and i t has been noted that d i f f e r e n t i a t i o n of limb buds may be somewhat asynchronous on the r i g h t and l e f t sides (Lenz, 1969; Mshimura & Yamamura, 1969). By the end of the s i x t h week a l l i n t e r d i g i t a l notches are present i n the feet and the notches between the fingers have become deeper and acutely angled (Horizon 20, morphological age 11). A bending i n the region of the elbow can now be seen. In the seventh week there i s elongation of the d i g i t s and separation into i n d i v i d u a l fingers and toes. "Touch pads" form at the taps of the d i g i t s . These features i n the development of the hands are character-i s t i c of morphological age 13 (Horizon 21-22) whereas they occur s l i g h t l y later, at morphological age 14, i n the feet. Towards the end of t h i s period of rapid morphogenesis d i g i t s two through four situate p a r a l l e l to each other (morpho-l o g i c a l age 15 i n the hands, and age 16 i n the feet, Horizon 22-23). The hands of an embryo (Horizon 22) with b i l a t e r a l ulnar Polydactyly whose limbs 4 are at approximately this stage of d i f f e r e n t i a t i o n are i l l u s t r a t e d i n the 1966 paper of Wishimura et a l . Around the s i x t h week when i n t e r d i g i t a l notches "become prominent on the hand plate, carpal elements begin to chondrify. Chondrification i n the d i g i t a l rays takes place around the seventh week in'conjunction with elonga-t i o n , and proceedsnin a proximodistal sequence (Gray et a l . , 1957). Histo-l o g i c a l studies (Lineback, 1921) on the hand of a 22 mm embryo with an accessory thumb attached at righ t angles to the base of the righ t f i r s t meta-carpal showed chondrification of digital.elements including an independent "phalanx" i n the accessory thumb. (Developmental age of the embryo has been estimated at Horizon 22.) I t i s also int e r e s t i n g to note that triphalangeal thumbs seen with thalidomide embryopathy are associated with maternal inges-t i o n of the teratogen around day 48 - 50 (Lenz, 1964, 1965), at approximately the time chondrification would be taking place. The f i r s t o s s i f i c a t i o n center appears at about eight weeks i n the terminal phalanx of the thumb, followed by centers i n the second, t h i r d and fourth fingers, and l a t e r the f i f t h - ( M a l l , 1906). However Gray et a l . (1957) note the f i r s t d i s t a l phalanx i s the l a s t to ossif y i n this sequence. Early i n the eighth week the second and t h i r d metacarpals begin to ossify, then the fourth and f i f t h , followed by the f i r s t . The proximal phalanx of each d i g i t o s s i f i e s after the metacarpal; a l l f i v e d i g i t s show o s s i f i c a t i o n centers about the end of the eighth week. In the tenth and eleventh weeks o s s i f i c a -t i o n begins i n the medial phalanges two through f i v e . At some point i n the normal d i f f e r e n t i a t i o n of the thumb there i s a proximal migration of the carpo-metacarpal j o i n t and rotation to a more ventral position (Gall et a l . , 1966). Data indicate o s s i f i c a t i o n begins i n the toes early i n the eighth week (Mall, 1906; Kraus, 1961). An o s s i f i c a t i o n center forms i n the terminal 5 phalanx of the f i r s t toe approximately 48 hours l a t e r than the corresponding center i n the thumb, and simultaneously with the fourth and f i f t h metacarpals and the proximal phalanges of the second and t h i r d fingers. The second, t h i r d and fourth metatarsals, followed by the f i r s t , then the f i f t h , are next i n sequence. D i s t a l phalanges of the t h i r d , second, fourth and f i f t h toes then ossify. An o s s i f i c a t i o n center i n the f i f t h d i s t a l phalanx i s not constant u n t i l about the end of the twelth week (Mall, 1906). O s s i f i c a t i o n appears i n the f i r s t proximal phalanx towards the end of the eleventh week; the second, t h i r d , fourth and f i f t h d i g i t s follow l a t e r . The sequence of medial phalanges two through f i v e begins to show o s s i f i c a t i o n around the s i x -teenth week and a center i n a l l f i v e has formed within the eighteenth week. Judging by the sequence of o s s i f i c a t i o n i n the d i g i t s , d i f f e r e n t i a t i o n i n i t i a t e s at the preaxial border of the hands and feet and this period of rapid development i s completed l a s t at the f i b u l a r border. The r a d i a l and f i b u l a r borders appear to be the most widely separated i n terms of the relative time at which developmental events occur and r a d i a l and f i b u l a r Polydactyly i n combination i s least common. T i b i a l and ulnar development appears to proceed at approximately the same time and Polydactyly of these borders i s a feature of polysyndactyly. However the most inter e s t i n g point which can be seen from the r e l a t i v e time at which d i f f e r e n t i a t i o n occurs concerns the ulnar and f i b u l a r borders. A dysfunction or i n s u l t of some type s p e c i f i c to the postaxial borders would catch the f i f t h toes at an e a r l i e r point i n the c r i t i c a l phase of morphogenesis and could be expected to effect a more severe malforma-t i o n . Variation i n extent of duplication could depend largely upon the r e l a t i v e point i n development at which normal d i f f e r e n t i a t i o n was interrupted and formation of an accessory d i g i t or d i g i t a l element began. A supernumerary ray. of the hand, recognizable:-; at morphological age 10, (or age 11 i f a d i g i t a l • 6 ray of the foot), which continued to develop i n sequence with the other d i g i t s would be expected to develop into a well-formed finger. Duplication solely of a d i s t a l phalanx or medial and d i s t a l phalanges could be i n i t i a t e d by a l a t e r error and f i r s t recognizablee during segmentation of the fingers when mesenchy-mal condensation of chondrification of accessory phalanges occurred. Regarding the formation of pedunculated accessory d i g i t s , Cummins (1932) f e l t that arrest of growth and d i f f e r e n t i a t i o n , especially of the basal portion, was responsible for the i r p a r t i c u l a r morphology. Variable location of ulnar pedicles, which ranges from the area around the head of the f i f t h metacarpal to-the region of the proximal interphalangeal j o i n t , might be imagined to res u l t from either of the following: (a) an accessory finger bud present l a t e r a l l y (morphological age 10), depending upon the degree of impairment i n d i f f e r e n t i a t i o n of that bud, could become located at some point off the l a t e r a l margin of the proximal phalanx of the f i f t h finger i n the subsequent rapid ex-tension of that finger; (b) a l t e r n a t i v e l y , the accessory could be i n i t i a t e d r e l a t i v e l y l a t e r i n the development of the hand and f i r s t become apparent as a finger bud off the extending f i f t h d i g i t . Its location would therefore be dependent upon the pa r t i c u l a r time at which i t began to d i f f e r e n t i a t e ; the potential of the tissue for f u l l development of a d i g i t could be considerably reduced i n direct proportion to the lag i n time between i t s i n i t i a t i o n and that of the other fingers. Following the technique of Nishimura and Yasuda (1969), the existence of time-specific v a r i a b i l i t y could perhaps be tested by observing the response of i n v i t r o cultures of limb buds to teratogens which induce Polydactyly. The concept of time-specific c r i t i c a l phases i n organogenesis i s often referred to when discussing the relationship of a cluster of defects as i n a syndrome. A number of authors, i n reference to the Holt-Oram syndrome, have commented that d i f f e r e n t i a t i o n of the primitive heart occurs during the fourth 7 to s i x t h weeks of gestation, corresponding with development of the upper limbs (Holt & Oram, 1960; Starke et a l . , 1967; Ashby et a l . , 1969). Temtamy (1966a) postulated there could be some time during the s i x t h or seventh weeks of embryo-genesis at which point dysfunction would i n t e r f e r e with c e l l u l a r d i f f e r e n t i a t i o n of the hypophysis c e r e b r i , the second phase of d i f f e r e n t i a t i o n of the r e t i n a , and extension and segmentation of the d i g i t s r e s u l t i n g i n hypophyseal obesity, r e t i n i t i s pigmentosa, and p o s t a x i a l Polydactyly c h a r a c t e r i s t i c of the Laurence-Moon-Biedl syndrome. Furthermore phenotypic overlap between t h i s syndrome and Carpenter's syndrome, marked however by the consistent occurrence of t i b i a l Polydactyly i n the l a t t e r , suggested the c r i t i c a l period f o r determination of Carpenter's syndrome was e a r l i e r . On the basis of d i f f e r e n t i a t i o n of the d i g i t s alone, t h i s l a s t conclusion may be questioned, considering that the appearance of notching on the ulnar periphery of the hand plate occurs p r i o r to that of the t i b i a l border, and the patient with p o s t a x i a l Polydactyly (Turner, 1931) included among cases of Carpenter's syndrome had quite rudimen-tary accessory d i g i t s . In a d d i t i o n thalidomide embryopathy has demonstrated there can be a high s p e c i f i c i t y f o r interference i n the morphogenesis of one border of the limbs. The teratogenic e f f e c t s of thalidomide provide the most conclusive evidence l i n k i n g d i g i t a l defects with other malformations. Lenz (1965) reported hypo-p l a s t i c t r iphalangeal thumbs and anorectal stenosis can both r e s u l t from maternal ingestion of thalidomide on day 48 - 50. The f a c t that a p l a s i a , hypo-p l a s i a and d u p l i c a t i o n of the thumbs and a t r e s i a of the eosophagus and of the anus can be caused by the s i n g l e agent, thalidomide, i s also of i n t e r e s t regarding the polydactyly/imperforate-anus/vertebral anomalies syndrome. Further evidence of correlated development of accessory d i g i t s and a d d i t i o n a l defects can be i n f e r r e d from findings of Nishimura et a l . (1966): the frequency of Polydactyly among enbryos of about three to ten weeks of age was. approximately 8 ten times i t s incidence among newborns suggesting a common association with defects incompatible with survival to term. 9 I I . Methods A. Ascertainment The study of Polydactyly i n the province of B r i t i s h Columbia began with cases ascertained through the B.C. Registry for Handicapped Children and Adults. This dictated i n large measure the time span of the project, as 1964— 1967 were the years for which the Registry had the best information on cases; 1963 had been the f i r s t year of a broader Registry program and information for 1968 was not yet complete when the study began. Cases were also ascertained by writing.to hospitals throughout the province, asking i f any children with Polydactyly were known to have been born or treated i n the hospital. This information could e a s i l y be extracted from disease indexes kept by most hospitals. Additional cases were referred by interested physicians and medical personnel, and from records of the Division of Medical Genetics, The University of B r i t i s h Columbia [U.B.C.]. Table I summarizes sources of ascertainment and information for the study. A t o t a l of 151 cases with Polydactyly born i n 1964 through 1967 were ascer-tained. The greatest number of cases o r i g i n a l l y came to attention v i a the Registry (114); the remaining cases were discovered through hospital records (30), Medical Genetics, U.B.C. (5) and r e f e r r a l s (2). I t should be noted that among the 37 cases, many were l a t e r found to be known to the Registry but for a variety of reasons had not been coded to Polydactyly. Thirteen cases were d i s -missed from the study because: (a) b i r t h of the proband within the province could not be es tablished. (6), (b) the limb malformation had been erroneously l i s t e d as Polydactyly (6), and (c) duplication of r e g i s t r a t i o n ( l ) , a c h i l d registered at b i r t h and under another name l a t e r after adoption. In most cases Polydactyly was noted p r i o r to hospital discharge of the newborn. However i n a few cases, especially those involving polysyndactylous duplication of a minimal nature, t h i s came to medical attention l a t e r and was 10 Table I. Sources of Ascertainment and Information Number of cases I. Probands i n the study 1. Ascertainment of cases (a) Registry 114 (b) Hospital records 30 (c) Medical Genetics, U.B.C. . 5 (d) Referrals 2 t o t a l T5T 2. Cases dismissed due to (a) B i r t h outside the province 6 (b) Wo Polydactyly 6 (c) Duplication of r e g i s t r a t i o n 1 t o t a l TS 3. Number of probands i n the study 138 I I . Follow-up interviews with families 1. No contact with parents or physician 13 2. Parents contacted (a) Unwilling to be interviewed 9 (b) Interviewed 82 (c) O r i g i n a l l y w i l l i n g but could not be located to arrange an interview 6 (d) L i v i n g outside province, o r i g i n a l l y w i l l i n g when contacted by l e t t e r 3 (e) Polydactyly unknown to parents, not interviewed 1 t o t a l T5T 3. Physician only contacted (a) Advised family not be interviewed 1 (b) Family moved outside of province 4 (c) Family could not be located 16 (d) Family previously seen i n Genetics C l i n i c 4 t o t a l .24 I I I . Review of medical records 1. Information from Public Health Nurse 4 2. Consultation through Genetics C l i n i c 6 3. Hospital records regarding (a) Delivery 134 (b) Description of supernumerary d i g i t s 131 11 recorded at the time of surgery. As i t was possible for a c h i l d with.Polydactyly to come to attention through a variety of sources and at any point from b i r t h to the age of approximately 2-g- to 6-g-, ascertainment for the, population i s thought to be quite complete. B. Follow-up Cases ascertained through the Registry were followed-up v i a the Public Health Units throughout the province. A l e t t e r was sent to the director of each unit informing the health unit of the study and requesting that parents and family physician of probands i n t h e i r area be contacted i n order to acquaint them with the study and secure the i r p a r t i c i p a t i o n . The health unit then relayed one of the following: (a) physician and/or family w i l l i n g (unwilling) to take part i n the project, (b) 'family moved, forwarding address enclosed (unknown), or (c) family unknown to the unit. Some families who were unknown or whose address was unknown to the respective health units could be followed-up i n the same manner as cases ascertained through hospital indexes. For these cases a l e t t e r was written to one of the attending physicians or the family physician informing him of the study and seeking his permission to contact the parents. Often the physician discussed the project, with the parents before replying and i t was a pleasant surprise to l a t e r f i n d the families knew about the study and were interested. Families previously seen i n Genetics C l i n i c and r e f e r r a l s could be approached d i r e c t l y regarding p a r t i c i p a t i o n i n the study. Neither of the two p r i n c i p a l methods of follow-up were completely s a t i s -factory since occasionally physicians or health units f a i l e d to reply. These were exceptions however. Often several attempts were made by the public health nurses, physicians, and the investigator to locate and contact a proband's family with the following r e s u l t s . In 13 cases the respective health unit was 12 not able to locate the family and i t was not possible to contact the family physician. These probands included f i v e given up for adoption. In 125 cases the parents ( 1 0 0 ) or the physician only ( 2 5 ) were contacted. Parents of nine probands.out of 100 were unwilling to participate and the physician of an additional c h i l d advised that the family not be disturbed. Families of 82 probands were interviewed i n t h e i r homes ( 7 2 ) , at the l o c a l health unit ( l ) or by telephone ( 9 ) . In seven other cases families were known to have moved out of the province. The mother.of another proband was unaware her c h i l d had had Polydactyly and no interview was attempted. The investigator was not able to locate and/or contact the remaining families ( 2 5 ) even though s i x of these had previously been located and indicated interest i n .the study and another three had been seen e a r l i e r i n Genetics C l i n i c . The greatest d i f f i c u l t y was to ob.t-ain current addresses for families since most could be interested i n p a r t i -cipating once they were contacted. Interviews were arranged with families w i l l i n g to participate by either phoning or w r i t i n g the parents. In most cases the v i s i t was made when a l l members of the immediate family were home i n order to obtain dermatoglyphics on everyone, sometimes including grandparents. In the course of an interview the family was asked to describe the proband's supernumerary d i g i t s , the super-numerary d i g i t s of any r e l a t i v e s , and a genetic family history was taken including d e t a i l s regarding the pregnancy. Most v i s i t s lasted one to two hours. Hospitals were contacted p r i o r to the investigator's a r r i v a l i n a town i n order to gain permission to review pertinent records. Information from the hospital charts of the mother and proband supplemented data obtained i n the interview, and comprised the bulk of information on families which were not interviewed. Public health nurses and nurses for the Department of Indian 13 A f f a i r s were also able to provide valuable information on s p e c i f i c families as were records from the D i v i s i o n of Medical Genetics, U.B.C. Addresses were obtained for three families which had moved out of the province. I t was decided to see whether a genetic history could be constructed for these probands from d e t a i l s off a questionaire. Parents responded to the f i r s t l e t t e r so questionaires and dermatoglyphic materials were sent to the famili e s . Unfortunately none were returned. A second l e t t e r was received from two families however which suggests a less complex form might have been successful. C. Incidence Incidence has been calculated according to birthdate of the probands with information on the t o t a l number of births i n the province taken from the 93rd (1964), 94th (1965), 95th (1966) and 96th (1967) Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia, issued by the Department of Health Services and Hospital Insurance. D. Racial background of probands Information on r a c i a l background of the probands was obtained from the parents, medical records of hospitals and the public health service, and the Registry (see Appendix A). Of greatest value was Registry data regarding Indian parentage (Indians native to western North America) which was available for most probands. Since this information i s s p e c i f i c a l l y requested on the Registry form, probands whose r a c i a l background was unknown have been assumed to be of non-Indian parentage. Census figures taken i n 1961 (1961 Census of Canada, Catalog 92-553, series 1 .3-2 , Table 82) do not give an analysis of population by r a c i a l back-ground, but th i s can be inferred from information on ethnic o r i g i n . The 14 following groups comprised the B.C. population between the ages of 15 and 44 i n 1961, roughly the age group of parents i n the study: native Indian and Eskimo 2.3 fo, A s i a t i c 2.6 fo, other and not stated 1.8 fo, and European (including Russian and Jewish) 93.9 f°. The overwhelming majority of the population i s Caucasian (57.7 fo of B r i t i s h or I r i s h extraction); Negros would appear to account for less than 1.8 fo. Newborns i n v i t a l s t a t i s t i c s f o r the province are noted to be of Indian or non-Indian parentage. Non-Indmansparentage i n analysis of r a c i a l back-gound has been equated with Caucasian. Figures used i n calculating incidence .were taken from Table 3 i n the 93rd (l964);and the 94th (1965) Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia and Table 11 i n the 95th (1966) and 96th (1967) Reports. E. Parental age Parental ages at the b i r t h of the proband were obtained from family i n t e r -views and medical records (see Appendix A). Control data on ages of parents for l i v e b i r t h s i n B.C. i n 1964 - 1967 were taken from 1964 - 1967 Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia. In these, information on paternal age i s given as the number of fathers whose age f a l l s within a five-year span, such as 25 - 29. MidpoBnt of each five-year span was taken for'calculations of mean paternal age: f o r ages 25 - 29 t h i s would be 27 years. The figures of 67 and of 18 years have been used for men whose age was l i s t e d as greater than 65 or less than 20. Maternal age i s given i n v i t a l s t a t i s t i c s by i n d i v i d u a l years.of age and consequently this control data i s not figured from the midpoint of a five-year span. 15 F. B i r t h order of the probands Pa r i t y of the mother was available from medical records i n most cases as well as being supplied i n the family interviews (see Appendix A). Control data on births i n the province was taken from the 1964 - 1967 Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia which gives b i r t h order of liveborn children according to maternal age. G. Extent of duplication Details on the extent of duplication were obtained from various sources with a minimal amount of c o n f l i c t i n g data. When available, descriptive i n f o r -mation regarding supernumerary d i g i t s of the probands was taken from radiology and pathology reports and surgical procedure summaries i n hospital charts. In some instances these reports reflected meticulous attention to the vascular, muscular and s k e l e t a l components of the duplicated fingers and/or toes. How-ever i t was not unusual for d i g i t s l i g a t e d p r i o r to hospital discharge of the newborn to receive only a b r i e f comment, perhaps tucked among the nurses notes: "extra fingers t i e d off" i n a.m. on day four. Such rudimentary forms might be further described as a "skin tag" .or "pedicle"; no d i s t i n c t i o n i s made between the two i n this study since i t i s not possible to know what an i n d i v i -dual physician infers by each term. In nearly a l l families interviewed, the parents saw the infant's extra d i g i t ( s ) . Thus parents were able to give t h e i r observations of the accessory d i g i t ( s ) such as: r e l a t i v e s i z e , location perpendicular or horizontal to the other digits,.suggestion of bony or cartilaginous elements, a b i l i t y to move independently,, presence of a n a i l , etc. Although the proband i n nearly every family v i s i t e d had had the supernumerary digitus) removed, i t was s t i l l possible to gain valuable information by observing the placement of the t r i r a d i u s associated with the supernumerary d igi t and i t s relationship to the scar that 16 remained (see Appendix B). In addition to interviews with families and a review of hospital records, for some cases information was obtained by con-tacting a family's physician or the public health nurses. A summary of the information gathered i s provided i n Appendix A. Organi-zation of the cases according to form of duplication has been as objective as possible. Where confusion-exists regarding the extent of duplication, the tendency i s to (classify the case "unknown". H. Genetic family history . . A genetic family history was taken for the families interviewed by the investigator and was available on families seen previously i n Genetics C l i n i c (see Appendix A). For the remaining probands a pedigree has been constructed as f u l l y as possible from hospital and public health records. These records rarely contain information regarding the presence of Polydactyly i n other family members. Consequently pedigrees derived from medical records i n which no additional family members are noted to have Polydactyly may actually have a positive history for supernumerary d i g i t s . Calculations on the percentage of probands with a pa r t i c u l a r type of duplication who have a family history of Polydactyly are baseid only on the families which have been interviewed. I. Multiple congenital anomalies Occasi'ib.:nia;lly anomalies i n addition to Polydactyly were noted i n various records on the probands.. Additional anomalies include those detected i n the newborn period and subsequently, i n some cases up to about f i v e years of age. Except for hands and feet, the probands of families interviewed were not examined by the investigator i n this study. Anomalies enumerated i n Appendix A were taken i n most cases from hospital charts or other medical records; i n only a few cases did a defect come to attention s o l e l y during the interview with the parents. As no special measures were taken to determine additional anomalies among the probands, the findings represent a minimum estimate of the frequency of other anomalies among polydactylous children. 18 I I I . Geographical D i s t r i b u t i o n A. Results and discussion Geographical d i s t r i b u t i o n by birthplace of the cohort i s l i s t e d i n Table I I according to c i t i e s which can be located on the accompanying map. The d i s t r i b u t i o n of births does not appear to deviate from that of the general population and cluster analysis was not attempted. I t was interesting to learn that one family with a history of supernumer-ary d i g i t s residing at present i n Prince George prided i t s e l f on descent, from' an i l l u s t r i o u s polydactylous pirate who had l i v e d on the coast of Vancouver Island. E f f o r t s were made to trace the account further but with no success. None of the probands appeared to be d i r e c t l y related to each other, although several of them had polydactylous r e l a t i v e s i n B r i t i s h Columbia. Table I I . Geographical D i s t r i b u t i C i t y No. of cases Vancouver Island Campbell River 2 Tofino 1 Port Alberni 2 Nanaimo 2 Duncan• 3 V i c t o r i a 8* Coastal Area Prince Rupert 1 Terrace 1 Kitimat 1 Powell River 1 Vancouver 37 North Vancouver 7 Burnaby 5 New Westminster 9 Surrey 6 Fraser Valley Haney 4 Langley 1 Mission 1 Chilliwaek 2 19 of Probands by Birthplace City No. of cases Central Int e r i o r Area Fort St. John 3 Dawson Creek 3 Prince George 1 2 Burns Lake 1 Williams Lake 3 South Central Area Kamloops 7 M e r r i t t 1 Salmon Arm 1 Vernon 2 Penticton 3 South Eastern Area Grand Forks 1 Nakusp 1 Castlegar 2 Nelson 2 Creston 1 Kimberley 1 ^Mother of one c h i l d resided i n Prince George during f i r s t trimester. F i g . 1. Map of the Province of BRITISH COLUMBIA MAIN HIGHWAYS, CITIES a TOWNS Scolt ° IO A> JO *0 DOMINION MAP LIMITED 626 HOWE ST., VANCOUVER ac. 21 IV. Incidence Polydactyly i s an anomaly amenable to incidence studies among newborns as pointed out by Neel (1958) and of considerable interest due to the hetero-geneous etiology of the defect. The incidence of Polydactyly found i n a num-ber of previous studies i s given i n a br i e f l i t e r a t u r e review f o r comparison with the B.C. findings. Incidence i n B.C. i s presented i n th i s section by year and month, by r a c i a l o r i g i n , and by sex. The incidence of sp e c i f i c types of accessory d i g i t s appears i n the section pertaining to the various forms of Polydactyly. A. Literature review Incidence of Polydactyly has been found to vary between different r a c i a l groups and subgroups. Findings from quite comparable studies on different populations are given i n Table I I I . Pooling data from these studies gives the following incidence per 1,000 births according to race: Negro (11 -9), [East] Indian (1.25), Chinese (1.15), Malay (1.05), Japanese (1.02) and Caucasian (0.90). These figures tend to obscure v a r i a t i o n i n incidence between people native to diff e r e n t 'geographical areas or of different ethnic background. Handforth (1950) studied a Chinese prison population and found the polydacty-lous individuals were a l l native to Kwangtung province. However the most extraordinary example i s the small' town i n Spain v i s i t e d by De Linares (1930) where the majority of the population had supernumerary d i g i t s . The results of separate studies on the incidence of Polydactyly are not always d i r e c t l y comparable. Several factors may contribute to var i a t i o n i n incidence estimates. Accessory d i g i t s , p a r t i c u l a r l y rudimentary forms of d u p l i -cation, may not be noted i n an infant's chart r e s u l t i n g i n cases missed when ascertainment i s through medical records. A study may s p e c i f i c a l l y exclude cases with rudimentary skin tags, cases which have congenital anomalies i n Table I I I . Incidence of Polydactyly i n Different Races Reference Locality Race Affected/N Incidence per 1,000 births Tan (1969) Singapore Malay 5 / 4,741 1.05 ( l i v e births) Tan (1969) Singapore [East!] Indian 3 / 2,390 1 .25 ( l i v e births) Tan (1969) Singapore Chinese 34 / 28,879 1.15 ( l i v e births) Mitani (1943) Japan Japanese 57 / 49,645 1.15 (? l i v e & s t i l l births) Neel (1958) Japan Japanese 60 / 64,569 0.93 ( l i v e & s t i l l b irths) Simpkiss & Lowe (1961) Uganda Negro 29 / 2,068 14.0 ( l i v e & s t i l l b irths) M e l l i n (1963) U.S.A. Negro 27 / 2,523* 10.68 ( l i v e & s t i l l births) Chung & Myrianthopoulos U.S.A. Negro 217 / 16,959 12.8 ( l i v e & s t i l l births) (1968) / Saldanha (1964) B r a z i l Negro 23 3,286 7.0 ( l i v e births) Saldanha (1964) B r a z i l Mulatto 20 / 3,804 5.2 ( l i v e births) Saldanha (1964) B r a z i l Caucasian 38 / 15,532 2.4 ( l i v e births) Ehrat (1948) Switzerland White 20 / 50,147 0.40 (? l i v e & s t i l l births) Book (1951) Sweden Caucasian 30 / 44, 109 0.68 ( l i v e & s t i l l b irths) Chung & Myrianthopoulos U.S.A. White 23 / 16,385. 1 .4 ( l i v e & s t i l l b irths) (1958) / ( l i v e & s t i l l b irths) M e l l i n (1963) U.S.A. White 5 3,215** 1 .56 Note: Cases of Polydactyly with additional congenital anomalies are included except i n the studies of Simpkiss & Lowe (no polydactylous infants with additional defects), and of M e l l i n and Saldanha (information not given). *44 fo of 5,735 **56 fo of 5,735 23 addition to Polydactyly, and s t i l l b o r n infants or aborted fetuses. In addition a study may f a i l to consider the importance of r a c i a l background upon incidence. An extremely high incidence of Polydactyly r e l a t i v e to other races has been found among Negro people i n A f r i c a , the U.S., and elsewhere. However i n a study of Negro births i n Baltimore, Frazier (i960) found only a moderately high incidence (3.6) which was nearer that of Mulattos of B r a z i l (5.2). Although mixed parentage w i l l have contributed to the reduced frequency, the method of ascertainment may have been the p r i n c i p a l factor as cases were as-certained from information on b i r t h c e r t i f i c a t e s . I t i s quite l i k e l y that skin tags (ulnar), the most common form of Polydactyly among Negros, were often not recorded. S i m i l a r l y i n a Nigerian study (Gupta, 1969), Polydactyly was considered an anomaly only when a phalanx and n a i l were present and cases with multiple anomalies were classed under the major malformation. As a res u l t 12 out of 4,220 newborn infants were l i s t e d as having Polydactyly, an incidence of 9.7 compared to the figure of 14.0 found by Simpkiss and Lowe (1961) i n Kampala. I t i s possible births among a small proportion of the population, such as Negro b i r t h s , include most polydactylous newborns. This was found i n New York by Bick (i960). In his studymPuerto Ricans accounted f o r the largest percentage of the population (58 fo) compared to White (21 %) and Negro (23 %) components, but s i x out of nine infants with Polydactyly among 5,000 newborns were Negro. Incidence among Japanese, Chinese and Caucasian people i s approximately the same, however the form of duplication commonly seen varies. Thumb Poly-dactyly i s most often presented by Oriental infants (Tan, 1969; Handforth, 1950; Stevenson et a l . , 1966) whereas the postaxial border i s usually affected among Caucasians (Stevenson et a l . , 1966). Co n f l i c t i n g data i s found i n the l i t e r a t u r e on th i s l a s t point. This appears to result from the means of as-24 certainment i n i n d i v i d u a l studies. Obviously i f patients are ascertained as s u r g i c a l cases the rudimentary skin tag forms of Polydactyly w i l l be missed, and the greatest proportion of these are po s t a x i a l . B. Incidence i n B r i t i s h Columbia by year, 1964 - 1967 A t o t a l of 138 polydactylous infants born i n B.C. i n the years 1964 -1967 were ascertained ( r e f e r to l i n e 3 of Table i ) . B i r t h s are set out by year i n Table IV and the incidence computed. Incidence over the years 1964 -1967 among liveborn infants i s 1.02 per 1,000. This value changes very l i t t l e when s t i l l b i r t h s * (20+ weeks gestation) are included: 138 out of 136,730 or 1 .01 per 1,000 newborns. Only one of the probands i s known to have been s t i l l b o r n . 1966 had the highest incidence of the four years. When projected incidence f o r 1968 which i s estimated to range between 0.92 and 1.19 per 1,000 b i r t h s i s considered as we l l , the 1966 peak appears to be a "normal" v a r i a t i o n . Two things suggest the 1966 peak i s not due to better r e g i s t r a t i o n of cases i n that year compared to the other three. The number of cases of Polydactyly ascertained through sources other than the Registry i s not notably d i f f e r e n t f o r the four years: four cases (1964), nine cases (1965), f i v e cases (1966) and seven cases ( 1 9 6 7 ) . In addi t i o n there i s no s t r i k i n g trend f o r the incidence of other anomalies estimated from Registry data to peak i n 1 9 6 6 . As can be seen from Table V a sing l e form of Polydactyly, ulnar d u p l i -cation, appears to be responsible f o r the increased incidence of supernumer-ary d i g i t s i n 1966. Common fac t o r s i n the h i s t o r i e s of the ulnar cases have not been detected. ^ f i g u r e s on s t i l l b i r t h s i n B.C. from Tables 27 ( 1 9 6 4 , 1965) and 35 ( 1 9 6 6 , 1967) i n the 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia Table IV. Incidence of Polydactyly i n B r i t i s h Columbia, 1964 - 1967 1964 1965 1966 1967 Total probands 30 30 44 34 138 l i v e b i r t h s * 35,897 33,669 32,502 32,899 134,967 incidence 0.84 0.89 1.35 1.03 1.02 (per 1,000) 25 *from Tables 3 (1964,1965) .and .11 (1966, 1967) i n the 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia 26 Table V. Number of Cases of Specific Types of Polydactyly i n 1964 - 1967 Type o f P o l y d a c t y l y 1964 1965 1966 1967 r a d i a l 9 0 ) ' ' # 8 (2) 7 (1 ) t i b i a l 1 2 1 2 u l n a r 9 11 (3) 23 (3) 11 (3) f i b u l a r 5 (1 ) . 6 7 6 (1 ) u l n a r & f i b u l a r 3 0?) 3 (1) 3 7 (5) u n k n o w n 3 1 .2 (1 ) 1 (1 ) t o t a l 30 30 44 34 Note: Number of cases with multiple major anomalies indicated i n parentheses. 27 C. Incidence i n B r i t i s h Columbia by month Cases, p a r t i c u l a r l y those born i n 1966, were scrutinized i n an attempt to detect clustering. Month of b i r t h of the probands i s tabulated i n Table VI. Comparing, in d i v i d u a l months, the greatest number of probands were born i n May 1966; however births were not p a r t i c u l a r l y frequent i n May for other years. Coincident month of b i r t h was the only apparent factor shared by the probands with birthdays i n May 1966;, the number with a similar-type of duplication or close proximity of birthplace was not s t r i k i n g . An increased number of probands were born i n May and i n July proportionate to l i v e births for the province whereas incidence i n January and October was lowest. Three-month spans 1964 - 1967 show seasonal incidence for February-March-April (0.95), August-September-October (0.98) and November-December-January (0.97) approximates the overall value of 1.02 whereas May-June-July i s (1.19) higher. The s l i g h t l y increased incidence of Polydactyly pertains to infants conceived i n August-September-October. Exclusion of cases with multiple major anomalies known to,show an increased association with Polydactyly and exclusion of a l l cases with multiple major anomalies give . a si m i l a r frequency p r o f i l e by month. . Consequently the temporal d i s t r i b u t i o n of cases with Polydactyly does not appear to be altered by the inclusion of cases with multiple congenital anomalies. D. Incidence and i i a c i a l o r i g i n Racial o r i g i n of most of the probands i s Caucasian, however there are a few children i n the study known to be of Chinese (2) or of North American Indian (10) descent. Racial background of newborns i s distinguished only as "native Indian" or non-Indian i n v i t a l s t a t i s t i c s for the province. Non-Indian can be equated with Caucasian without too great an error because there i s no sizeable population of Negro people i n the province and the largest 28 Table VI. Incidence of Polydactyly i n British Columbia by Month Number of probands born in 1964 1965 1966 1967 Incidence* per 1.000 liv e births January 5 - 1 2 0.73 ( 8) February 1 6 3 1 1.05 (11) March 2 4 2 3 0.93 (11) Apr i l 1 2 2 5 0.87 (10) May 2 2 : 9 • 2 1.26 (15) June '1 . 2 6 .' 2 0.96 (11) July 4 6 2 4 1.35 (16.) August 6 - 3 4 1.14 (13) September 2 3 4 3 1.04 (12) October 2 2 3 1 0.73 ( 8) November 2 1 7 3 1.27 (13) December 2 2 2 4 0.93 (10) total 30 30 44 34 138 *figures on live births i n B.C. from Tables 46 (1964, 1965) and 44 (1966, 1967) i n the 93rd, 94th, 95th and 96th Reports on V i t a l Statistics of the Province of Bri t i s h Columbia 29 non-Caucasian group among non-Indians i s of O r i e n t a l descent (see p. 14). Studies i n d i c a t e P o l y d a c t y l y among Japanese (Neel, 1958) and Chinese (Tan, 1969) people has an incidence s i m i l a r to that of Caucasians, consequently the O r i e n t a l p o p u l a t i o n of B.C. i s not expected to d i s p r o p o r t i o n a t e l y i n f l u e n c e the incidence f i g u r e f o r non-Indians. I n c l u d i n g probands about whom no comment was made regarding r a c i a l background i n the non-Indian group, the incid e n c e of P o l y d a c t y l y i n 1964 - 1967 among l i v e b o r n Caucasians of B.C. was 128 out of 126,244* or 1.01 per 1,000. I t i s impossible to estimate the extent to which non-Indians have c o n t r i -buted to the incidence of P o l y d a c t y l y among the n a t i v e Indian p o p u l a t i o n . V i t a l s t a t i s t i c s a v a i l a b l e on "native Indians" r e s i d i n g w i t h i n the province " r e f e r to Indians by r a c i a l o r i g i n , i n c l u d i n g r e g i s t e r e d Indians l i v i n g on or o f f r e s e r v e s , and enfranchised Indians, some of whom may be of mixed descent" (93rd Report on V i t a l S t a t i s t i c s of the Province of B.C., p. M17). Both parents of at l e a s t three, and p o s s i b l y four of the probands are of predominantly Indian descent. In another case both parents are of Indian-Caucasian descent, and i n the remaining cases only one parent i s Indian (3) or one parent i s Indian-Caucasian ( 2 ) , and the other parent i s Caucasian (2) or of unknown r a c i a l background ( 3 ) . Probands appear to be descended from at l e a s t seven d i f f e r e n t Bands q u i t e d i s t a n t from one another. Acknowledging the inherent l i m i t a t i o n s , t h i s study found ten c h i l d r e n w i t h P o l y d a c t y l y among 8,723* l i v e b o r n "native Indian" i n f a n t s , an incidence of 1.15 per 1,000. In the group of Indian c h i l d r e n d u p l i c a t i o n i s p o s t a x i a l i n eigh t cases and r a d i a l i n two cases. Among p o s t a x i a l cases are three probands w i t h u l n a r and f i b u l a r P o l y d a c t y l y , two of which have m u l t i p l e c o n g e n i t a l anomalies, one proband w i t h u l n a r , and four probands w i t h f i b u l a r P o l y d a c t y l y . To f i n d * f i g u r e s on Indian b i r t h s i n B.C. from Tables 3 (1964, 1965) and 11 (1966, 1967) of the 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia f i b u l a r accessory d i g i t s more common than ulnar among these Indian children i s i n contrast with the findings for the t o t a l B.C. population. Four of the si x children without multiple congenital anomalies (postaxial cases) are d e f i n i t e l y known to he of mixed descent. Thus i t could be postulated that postaxial duplication has primarily been introduced by non-Indian elements. Furthermore i t s expression could be influenced by modifying factors which are charact e r i s t i c of the Indian gene pool. Detailed r a c i a l background i s known for one of the two probands with r a d i a l Polydactyly. In that case the parents are u n l i k e l y to be of mixed descent. Thus i t can be speculated that duplication of the thumb was the form of Polydactyly o r i g i n a l l y most frequent among the Indians. This hypothesis i s reasonable considering the theory American Indians are of mongoloid extraction (jenness, 1955). Detection of a hemoglobin variant common to Chinese and to North American Indians (Blackwell et aX, 1963) supports the theory of a l i n k between the two peoples. In addition i t i s i n t e r e s t i n g that f i b u l a r Polydactyly was more common than ulnar i n the predominantly Chinese population studied by Tan (1969). E. Incidence by sex The sex of the developing fetus appears to affect the expression of Polydactyly as can be seen by the incidence of supernumerary d i g i t s among male and female liveborn infants given i n Table VII. Over the four years incidence i s 1.38 (95 / 68,956) among males and Q265 (43 / 66,011) among females, a sex r a t i o of approximately 2 : 1 . Cases are further c l a s s i f i e d according to form of duplication and sex i n Table XIV. The disproportionate number of affected males i s c h a r a c t e r i s t i c of the anomaly and not limi t e d to Caucasians. A sex r a t i o of 1 .8 : 1 was found among 81 polydactylous newborns i n Sao Paulo (Saldanha, 1964); a sex r a t i o Table VII. Incidence of Polydactyly among Males and Females i n B r i t i s h Columbia, 1964 - 1967 probands liveborn infants* incidence 1 96j males females 19 11 18,390 17,507 1.03 0.63 1 965 males females 20 10 17,110 16,559 1.17 0.60 1 9616 males females 29 15 16,625 15,877 1.74 0.94 . 1 96r7 males females 27 7 16,831 16,068 1.60 0.43 ^figures from Tables 3 (1964, 1965) and 11 (1966, 1967) of the 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia 32 'of 2.2 : 1 was observed by M e l l i n (1 963) - Findings of Boot (1951 ) did not demonstrate a large excess of affected males. Among 30 infants with Poly-dactyly there were 16 males (0.70 per 1,000) and 12 females (0.56 per 1,000) plus two cases of unknown sex. Incidence among females i n Sweden (Book, 1951) was very s i m i l a r to findings for the years 1964 and 1965 i n B.C. whereas incidence among males was considerably lower than the B.C. figure. 33 V. Parental Age and Parity-Maternal age and b i r t h order have been shown to be factors i n the etiology of congenital anomalies i n a few instances. There i s a correlation between infants born with a trisomic chromosomal complement and increased maternal age (Penrose, 1933; McKusick, 1969); McKeown (1961) reported a greater incidence of harelip with increased maternal age and a raised incidence of anencephalus among f i r s t - b o r n . Wright (1926) working with inbred strains of guinea pigs found polydactylous progeny were much more frequent i n l i t t e r s born to younger females. Thus i t i s of interest whether maternal age or parity among mothers of the probands appears to vary from that of the population of women i n B.C. who delivered infants i n 1964 - 1967. A. Results and "discussion The mean age of women who delivered liveborn infants i n the test period i n B.C. was 26.0. The mode decreased from 23 years of age i n 1964 to 20 i n 1967; considering the t o t a l four year span, 1964 - 1967, i t was 23. Paternal-age averaged 30.0, having it's mode the age range of 25 to 29 years. These figures correspond closely' with mean maternal and paternal ages of the probands' parents, given i n Table V I I I . Grouping cases by affected border of the limbs, the only ones for whom parental age shows much v a r i a t i o n from control figures are children with t i b i a l Polydactyly and children f o r whom the affected border i s unknown. Both are categories which involve a small number of cases. For comparison, i n Kampala the mean maternal age of mothers of polydactylous infants was 23.6 corresponding to a mean for a l l mothers of 24.2 (Simpkiss and Lowe, 1961). . Table IX presents mean parental age at the b i r t h of male and of female probands, with cases grouped according to affected border of the limbs. In general, parental age averages s l i g h t l y higher for polydactylous female infants Table V I I I . Mean Parental Age at the B i r t h of the Probands Maternal age Paternal age Border affected No. of cases averaged*/N Mean No. of cases averaged*/N Mean r a d i a l 31/31 26.1 20 /31 32.0 t i b i a l 5 / 6 21.8 3 / 6 26.6 ulnar 54 / 54 26.5 36 / 54 31.3 f i b u l a r 23 / 24 26.8 15 / 24 31.1 ulnar & f i b u l a r 16 / 16 26.1 12 / 16 28.1 a l l postaxial 93 / 94 26/5 63 / 94 30.6 border unknown 5 / 77 30.8 1 / 7 53.0 a l l cases 134 /138 26.4 87 /138 31.0 a l l B.C. b i r t h s * * 26.0 30.0 *number of cases involved i n calculating the mean out of the t o t a l number with that type.of duplication **figures on l i v e births i n B.C. from Tables 49 (1964, 1965) and 46 (1966, 1967) of the 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s of the Province of B r i t i s h Columbia Table IX. Mean Parental Age at the B i r t h of Male and of Female Probands Maternal age Paternal age Male probands Female probands Male probands Female probands-cases t o t a l cases t o t a l cases t o t a l cases t o t a l without no. of without no. of without no. of without no. of m.m.a.* cases m.m.a. cases m.m.a. cases m.m.a. cases r a d i a l 24.7+ 1/2 25.8+ 1.3 28.0+ 2.4 27.0+ 2.3 30.4+ 1.8 32.2+ 1.8 31.6+ 2.0 — t i b i a l 22.0 24"r5- 21.5 — 25.5 — 29.0 — ulnar** 24.5+ 1.0 25.3+ 0.9 29.7+ 1 .7 28.9+ 1.6 28.2+ 1 .2 30.0+ 1.4 35.7+ 2.6 33.6+ 2.2 f i b u l a r * * * 26.3+ 1.7 27.1+ 1.7 25.0+ 2.6 26.1+ 2.5 28.4+ 1 .9 29.8+ 2.2 31.6 32.2 ulnar & f i b u l a r 27.4+ 2.6 26.6+ 1.9 28.8+ 4.1 27.7+ 3.5 32.0+ 4.3 31.3+ 3.0 29;5+ 4.6 28.4+ 3-7 *multiple major anomalies **case number 78 (polysyndactyly) excluded from table; case number 86 included among ulnar & f i b u l a r cases ***cases numbers 93 and 110 included among ulnar & f i b u l a r cases 36 and there i s the suggestion sex r a t i o v aries i n v e r s e l y with increasing maternal age. This i s not due to cases associated with multiple major malformations since parental age f o r female probands with multiple congenital anomalies averages' le s s (paternal, 29.2; maternal, 24.8) than f o r male probands with multiple congenital anomalies (paternal, 35.8; maternal, 29.1). Exclusion of cases with multiple major anomalies widens the discrepancy between mean parental age f o r male and f o r female probands.(male probands: paternal 29.1, maternal 25.1; female probands: paternal 32.2, maternal 27.8). Considering i n d i v i d u a l types of du p l i c a t i o n , the greatest difference between mean parental age of male and of female probands i s seen among ulnar cases without multiple major anomalies (P<.01). With a la r g e r sample a s i g n i f i c a n t increase i n parental age might also be demonstrated among females with other types of Polydactyly. D i s t r i b u t i o n of cases with Polydactyly according to p a r i t y and maternal age and to p a r i t y along (Table X) resembles that of a l l infants born i n B.C. i n 1964 - 1967. There appears to be l i t t l e d i f f e r e n c e between b i r t h order of female probands compared with male and no recognizable trend of increasing or decreasing sex r a t i o among probands born to women of higher p a r i t y . For comparison, i n Kampala i t was noted the mean b i r t h order of polydactylous infants was 2.00; the mean f o r a l l b i r t h s was 2.34, (Simpkiss & Lowe, 1961). Table X. Birth Order of the Probands and.of Live Births in British Columbia, 1964 - 1967 Birth order (no. of cases expressed as a percentage of the total) 1 2 3 . 4 5 6 7 8 9 10-14 15+ B.C. births* 33.0 25.8 17.3 10.5 5.8 3.1 1 .8 1 .1 0.7 '0.8 0.1 probands** 29.4 24.3 22.8 11.8 2.2 3.7 0.7 2.9. - 2.2 *figures on live births in B.C. from Tables 5 (1964, 1965) and 13 (1966, 1967) of the 93rd, 94th, 95th and 96th Reports on Vital Statistics of the Province of British Columbia **information unavailable for two cases Total number of cases 134,967 136 38 VI. Forms of Polydactyly A. Introduction Supernumerary d i g i t s occur on the p o s t a x i a l and/or p r e a x i a l borders of the hands and f e e t . P r e a x i a l commonly re f e r s to the f i r s t and second d i g i t s and p o s t a x i a l to the t h i r d , fourth and f i f t h . The terms are so used i n t h i s paper. Sometimes i n a discussion of Polydactyly p o s t a x i a l w i l l be specifically designated to p e r t a i n to the f i f t h d i g i t s only, and p r e a x i a l to the f i r s t . The second, t h i r d and fourth d i g i t s are then r e f e r r e d to as c e n t r a l d i g i t s . . This system emphasizes that Polydactyly i s nearly always immediately l a t e r a l or medial to the f i r s t and f i f t h d i g i t s , but disregards the f a c t that d u p l i -cation of the second d i g i t i s u s u a l l y quite a separate anomaly from that•of the t h i r d or fourth. Usually only one supernumerary d i g i t i s present on a limb with one or both hands and/or feet affected. Among posta x i a l cases i t i s not unusual for hands and feet both to be affected; however r a d i a l d u p l i c a t i o n most often occurs alone and cases with r a d i a l and t i b i a l Polydactyly are infrequent. In polysyndactyly both the p o s t a x i a l and the p r e a x i a l borders may be affected, but u s u a l l y d u p l i c a t i o n i s l i m i t e d to one border of the hands and/or f e e t . Occasionally there may be two (or three, r a d i a l ) accessory f i r s t or f i f t h d i g i t s , one'accessory f i r s t d i g i t and one f i f t h , one accessory t h i r d or fourth d i g i t and one f i f t h , or more unusual combinations of p o s t a x i a l and p r e a x i a l d u p l i c a t i o n . Bunnell (1956') discussed a case presenting seven fingers and no thumb with duplicated middle, ring, and f i f t h fingers f l a n k i n g the index r a d i a l l y . There was d u p l i c a t i o n of the ulna and absent radius. Temtamy (1966b) described a patient with eight toes on the l e f t foot: one b i g toe, complete d u p l i c a t i o n i n c l u d i n g the metatarsal of the second (syndactylous), t h i r d and fourth toes, and a s i n g l e f i f t h toe. More bi z a r r e cases with as many as t h i r t e e n d i g i t s on a limb have been noted (Voight, c i t e d by Farabee, 1903). 39 Polydactyly occurs quite often i n association with syndactyly. In some cases there may only be minimal webbing of the second and t h i r d toes, a frequently occurring minor anomaly considered to be a normal v a r i a t i o n . Others present a supernumerary d i g i t syndactylous with the corresponding p r i n c i p a l d i g i t , a common form of duplication of the f i b u l a r , t i b i a l , and less often, the r a d i a l borders. With these the accessory and the p r i n c i p a l d i g i t comprise a broad finger or toe which may be somewhat b i f i d d i s t a l l y and syndactyly i s lim i t e d to the two d i g i t s . Polydactyly i s also found i n cases where two of the normal f i v e toes and/or fingers exhibit an anomalous extent of webbing. I t i s th i s type of association which s h a l l be referred to as a polydactyly-syndactyly complex. Neel (1958) reported 38 cases with Polydactyly as the only noted anomaly and Polydactyly with syndactyly i n 11 cases. These do not include cases with multiple congenital anomalies. The type of syndactyly present i n the 11 cases was not specified. This number seems too high to consist only of cases with a polydactyly-syndactyly complex. In c l a s s i f y i n g cases presenting a polydactyly-syndactyly complex, B e l l (1930) noted that family h i s t o r i e s of syndactyly i n association with supernum-erary d i g i t s r a r e l y involved Polydactyly of the thumb or f i f t h finger. She designated the polydactyly-syndactyly combinations commonly seen as types A^ and B^. Type A^ often manifested as p a r t i a l or complete duplication of the fourth finger with syndactyly of the accessory, the t h i r d and the fourth fingers. B^  involved syndactyly of toes four and f i v e , often i n association with an accessory f i b u l a r toe. Temtamy (19660) modified the descriptions and c l a s s i f i e d types A^ and B^  as synpolydactyly. In addition she (Temtamy) defined a second type of polydactyly-syndactyly complex, polysyndactyly, i n which both postaxial and preaxial duplication may occur. Literature regarding forms of Polydactyly and polydactyly-syndactyly i s reviewed i n this section. Results of the B.C. study and discussion follow. 40 B. Thumb Polydactyly Radial duplication can be extremely variable. I t has been suggested that a " d u c k - b i l l " appearance (Haas, 1939) and r a d i a l deviation of the d i s t a l phalanx (Pott, 1884; De Marinis & Sobbota, 1957) are minor manifestations of polydactylous thumb. Accessory d i g i t s range from a pedicle or skin tag attached at the l a t e r a l border near the head of the f i r s t metacarpal to a f u l l y functional b i - or triphalangeal d i g i t . Duplication may be polysyndactylous or consist of two independent rays. Often there i s some degree of deviation of the accessory and/or p r i n c i p a l thumb ( M i l l e s i , 1967); occasionally the super-numerary d i g i t grows at rig h t angles to the carpometacarpal j o i n t (Handforth, 1950). Among the 13 cases of Handforth (1950), i n a l l but one the extra d i g i t was considered to be l a t e r a l , i . e . the radial-most ray. This agrees with the findings of Wassel (1969) i n which the accessory was l a t e r a l i n 20 out of 22 instances. In some cases the larger of the two thumbs i s functionally perfect. Often however i t i s rather small i n comparison to the thumb on the opposite hand and may present a variable degree of l a t e r a l rotation of the f i r s t metacarpal so that i t l i e s more i n the plane of the fingers. In extreme cases neither the p r i n c i p a l or the accessory thumb i s able to oppose the fingers (Handforth, 1950). Injury to the p r i n c i p a l thumb at the time the accessory i s removed may c o n t r i -bute to i t s small s i z e , and the degree of deviation present can be compounded as a result of surgery (Wassel, 1969). Extent of duplication can be c l a s s i f i e d i n the following way according to the point at which d i v i s i o n into two rays occurs (Wassel, 1969): (a) bifid d i s t a l phalanx, (b) duplicated d i s t a l phalanx, (c) b i f i d proximal phalanx, (d) duplicated proximal phalanx, (e) b i f i d metacarpal, (f) duplicated meta-carpal, (g) triphalangism and (h) pedicle. Complete duplication of the proximal phalanx, each with i t s own epiphysis or a common epiphysis a r t i c u -41 l a t i n g with a normal or a broad f i r s t metacarpal, has been the most common form of r a d i a l Polydactyly found i n several studies. Thirty-four out of 79 (43 f ) of the polydactylous thumbs i n a review of 70 cases seen at the Univer-s i t y of Iowa Hospitals had this type of duplication (Wassel, 1969). Handforth (1950) found i n over half of his 13 cases the accessory originated at the d i s t a l end of the metacarpal (10/16 thumbs), and this was the most frequent form of duplicated thumb (11/27 thumbs) among the 25 cases of Tan (1969). An approximation of the r e l a t i v e frequency of the forms of polydactylous thumb can be derived by pooling findings of the three aforementioned studies: b i f i d and duplicated d i s t a l phalanx comprised 16 fo (range: 13-18 fo) of the poly-dactylous thumbs, b i f i d and duplicated proximal phalanx 53 f> (range: 49-75 f°) and b i f i d and duplicated f i r s t metacarpal 14 f (range: 13-15 fo). However Stevenson et a l . (1966) state the majority of cases with r a d i a l Polydactyly have duplication of the terminal phalanx. Wassel (1969) t a l l i e d triphalangeal duplication separately (15/79 thumbs) whereas triphalangeal thumbs observed i n the studies of Handforth (1950) and Tan (1969) were included i n the above figures. Triphalangism accounts for 20 fo of the polydactylous thumbs i n the Iowa study and 23 f> of Handforth's cases. However Tan, whose study sets out incidence i n Singapore, shows a much lower frequency (4 f° or 1/25) among cases with r a d i a l Polydactyly. In addition Tan noted a number of cases i n which the supernumerary d i g i t had a "pedicle-type" attachment (6/25). Bony elements were present i n f i v e out of s i x cases but there was no osseous-:.union or a r t i c u l a t i o n with the p r i n c i p a l thumb. Radial duplication i s more commonly u n i l a t e r a l which can be seen from Table XI. The one study which represents incidence (Tan, 1969) found a r a t i o of approximately three rig h t [R|] to one l e f t [ l ] for u n i l a t e r a l [u] cases. A preponderance of cases with the righ t side affected has been noted i n other studies', and few individuals with b i l a t e r a l [B] r a d i a l Polydactyly. I t should 42 Table XI. Hand Affected i n Cases with Radial Polydactyly U n i l a t e r a l B i l a t e r a l Reference Right Left Total Total Farabee (1903) (34). (28) (62)* 28 Handforth (1950) 8 3 11 2 Barsky (1958) (16) ( 7) 24** 1 Temtamy (19661)) 5 2 7 Tan (1969) 18 5 23 2 Wassel (1969) (12) ( 2) 61*** 9 ^affected side unknown i n a number of additional cases **affected side unknown i n one case ***affected side known for 14 cases only 43 be pointed out that a disproportionate number of cases with b i l a t e r a l d u p l i -cation have a triphalangeal thumb(s). Incidence of r a d i a l Polydactyly i n Singapore was 25 / 36,427 or 0.69 per 1,000 l i v e births (Tan, 1969). Exclusion of cases with an accessory triphalan-geal thumb, a form of Polydactyly d i s t i n c t i n several respects from duplica-t i o n involving a biphalangeal thumb, gives an incidence of 0.66. Studies i n conjunction with the World Health Organization (Stevenson et a l . , 1966) found s i m i l a r incidence figures for r a d i a l Polydactyly among the Chinese: Hong Kong, 0.60 per 1,000; Singapore, 0.50 (l/20 mothers was Eurasian); Kuala Lampur, 0.46. Incidence among Caucasians was considerably lower: Melbourne, 0.13 and Belfast, 0.07 (Stevenson et a l . , 1966). C. Triphalangeal f i r s t d i g i t s Triphalangy as a preaxial anomaly can affect either the thumb and/or the f i r s t toes; three phalanges are present i n the f i r s t d i g i t rather than the normal two. I t i s more commonly seen on the hands than on the feet and may be associated with some degree of b i f i d duplication. In cases associated with an accessory r a d i a l d i g i t , the medial and/or l a t e r a l of the two rays can be triphalangeal. An in t e r e s t i n g review of cases p r i o r to 1903 was compiled by Farabee (1903) who cited a report by Reider (1900) of a boy whose l e f t thumb and index finger had four phalanges each. I t has long been debated whether hyperphalangy of the f i r s t d i g i t reflects a hypoplastic process, a duplication or the two i n combination. According to the l a t t e r view, triphalangy of t h e ' f i r s t d i g i t i s interpreted as absence of the true pollex (or hallux) and duplication of the second d i g i t (Joachimsthal, 1900; Barsky, 1958; Swanson & Brown, 1962). Lapidus et a l . (1943) have suggested that this hypothesis might be tenable i n cases where the thenar eminence i s absent. The'report of a mother with a triphalangeal l e f t thumb 44 whose son had b i l a t e r a l absence of the thumbs (Haas, 1939) could be considered support for this hypothesis, or for the concept that triphalangy i s a form of hypoplasia. Haas (1939) believed this l a t t e r view and proposed that the t r i -phalangeal state resulted from f a i l u r e of two d i s t a l phalanges of the f i r s t d i g i t to fuse. Further i t has been suggested that the presence of both prox-imal and d i s t a l epiphyses points to underdevelopment of the f i r s t metacarpal (Temtamy, 1966$). This i s not a consistent finding however, and some trip h a -langeal f i r s t rays have been noted to have a single proximal epiphysis or d i s t a l epiphysis. An alternate hypothesis considers triphalangy as an aborted form of Polydactyly, the middle phalanx being a remnant of the base of one of the phalanges of a b i f i d thumb (Lapidus et a l . , 1943). This concept of hyper-phalangy i s supported by the fact that triphalangeal f i r s t d i g i t s are frequently associated with duplication of phalanges or whole rays. Temtamy (19661a), i n order to reconcile the opposing views, suggested cases could be distinguished by the presence of a normal or abnormal f i r s t metacarpal. In her scheme, cases with an abnormal metacarpal show no association with Polydactyly. In addition, she recognized a t h i r d class: Polydactyly of the index finger. This included cases which represent the extreme among the possible variations of b i f i d f i r s t d i g i t , those i n which the f i r s t metacarpal i s completely duplicated and the ulnar of the two rays or the ulnar and the r a d i a l rays are triphalangeal (Lapidus & Guidotti, 1944). Because i t i s not clear whether the presence of an abnormal or normal f i r s t metacarpal i s as discriminate a factor as suggested, and due to the controversy over cases included as duplication of the second d i g i t , i t seems reasonable to consider the various forms of triphalangeal f i r s t d i g i t s as variations i n morphology which can re s u l t from the same processes as o l i g o - and Polydactyly. That abnormal triphalangy i s e t i o l o g i c a l l y related to both Polydactyly and r a d i a l hypoplasia can be seen from thalidomide embryopathy, from the range of defects 45 seen i n the Holt-Oram syndrome, and from the observation of patients with triphalangeal thumbs and imperforate anus, strongly suggestive of the poly-dactyly/imperforate anus/vertebral anomalies syndrome. There are two f u n c t i o n a l categories of triphalangeal thumbs (Swanson & Brown, 1962). In type I the triphalangeal d i g i t s are able to oppose the other fingers and the supernumerary middle phalanx i s u s u a l l y wedge shaped, resulting i n ulnar or r a d i a l deviation of the d i s t a l end of the thumb. This type i s more frequently u n i l a t e r a l and sporadic. In type II opposition i s not s a t i s -f actory, the triphalangeal d i g i t being long and often implanted i n the same plane as the other f i n g e r s . This type i s more frequently b i l a t e r a l with a p o s i t i v e family h i s t o r y . Triphalangeal thumbs, with or without an associated degree of b i f i d d u p l i c a t i o n , are more commonly b i l a t e r a l and f a m i l i a l i n contrast with poly-dactylous biphalangeal thumbs.' However b i l a t e r a l f a m i l i a l cases, e s p e c i a l l y those i n v o l v i n g r a d i a l d u p l i c a t i o n i n some member of the family, are more l i k e l y to come to a physician's a t t e n t i o n and be reported. The reviews of Stieve (1916) and of Swanson and.Brown (1962) l i s t e d 23 cases u n i l a t e r a l com-pared to 90 cases b i l a t e r a l , 67 out of 81 b i l a t e r a l cases occuring i n 19 f a m i l i e s . The sex r a t i o i s not equal due to an excess of a f f e c t e d males among cases reported (Swanson & Brown, 1962). An estimate of frequency was made by Lapidus et a l . (1943) who found three cases of triphalangeal thumbs associated with an accessory thumb among 75,000 draftees, one with a p o s i t i v e family h i s t o r y f o r the t r a i t . Incidence i n the study by Tan (1969) was 1 / 36,427 or 0.03 per 1,000 newborns. The incidence of triphalangeal thumbs without associated d u p l i c a t i o n appears to be unknown. 46 D. T i b i a l Polydactyly Very l i t t l e has been written regarding duplication of the f i r s t toes. T i b i a l Polydactyly occurs as a sal i e n t feature of polysyndactyly, but i t i s unknown i f t h i s special type of Polydactyly accounts for a considerable pro-portion of cases. Parabee.(1903) i n his massive review noted t i b i a l Poly-dactyly frequently associated with accessory d i g i t s of the hands. His data, extracted from a number of tables, i s presented i n Table X I I . Although the cases i n Table XII by no means represent incidence, they suggest supernumerary d i g i t s l i m i t e d to the t i b i a l border are more commonly b i l a t e r a l , i n contrast to r a d i a l Polydactyly. In addition the t i b i a l case reported by Egawa et a l . (1969) had b i l a t e r a l duplication. Approximately 29 % (13/45) of the cases t a l l i e d by Farabee had preaxial duplication of one or both limbs of the hands and feet and approximately 38 % (17/45) had t i b i a l plus ulnar accessory d i g i t s . I t i s strange there was no association of t i b i a l with f i b u l a r accessory d i g i t s , since most cases with postaxial and preaxial Polydactyly may well have been instances of polysyn-dactyly. Polysyndactyly w i l l probably also account for some of the t i b i a l plus r a d i a l cases. However a greater number may be t i b i a l cases associated with accessory triphalangeal thumbs si m i l a r to the reports of Hefner (1940) and Manoiloff (1931). E. Polydactyly of the index finger . Polydactyly of the index finger i s reported to vary from a skin tag attached at the proximal phalanx to some degree of duplication of the bony -elements of the normal second d i g i t (Wood, 1970). The accessory may be syn-dactylous to the index and the t h i r d (long) finger; i n one case syndactyly involved a l l the fingers(Cohn, 1932). I t may not be clear whether an anomalous r a d i a l d i g i t ( s ) represents a triphalangeal thumb or duplication of the index 47 Table XII. Frequency of Accessory Digi t s i n Conjunction with T i b i a l Polydactyly Affected border Wo. of cases t i b i a l duplication only R t i b i a l 1 L t i b i a l 4 B t i b i a l 4 t i b i a l and r a d i a l duplication R t i b i a l , L r a d i a l 1 L t i b i a l , B r a d i a l 3 B t i b i a l , L r r a d i a l 1 B t i b i a l , R r a d i a l 1 B t i b i a l , B r a d i a l 3 t i b i a l , r a d i a l and ulnar duplication B t i b i a l , B r a d i a l , B ulnar 4 t i b i a l and ulnar duplication L t i b i a l , B ulnar 2 R t i b i a l , B ulnar 5 B t i b i a l , R ulnar 1 B t i b i a l , B ulnar 5 t i b i a l duplication, no other d e t a i l s ? t i b i a l . 1 8 t o t a l 63 Source: Farabee (1903) 48 finger with absence of the thumb. Temtamy (1966b) suggests the l a t t e r cases may be distinguished by morphology and dermatoglyphics. Duplication of the index finger i s the type of Polydactyly reported to be least common (Kanavel, 1932; Barsky, 1958); among 145 patients with Polydactyly seen at the University of Iowa Hospitals there was a t o t a l of 204 supernumerary d i g i t s of which seven involved the index finger (Wood, 1970). F.. Polydactyly of the third, or fourth fingers Duplication of the t h i r d or fourth finger may be i n the form of a non-syndactylous accessory d i g i t (proband number 123) or polysyndactylous (Mathew, 1908; Kanavel, 1932; B e l l , 1953). Polydactyly of the f i f t h fingers and toes has been noted i n some individuals with an independent accessory t h i r d or. fourth finger. The polysyndactylous form described as synpolydactyly by Temtamy (l966bx) appears to be discussedmmost often i n the l i t e r a t u r e . This may not r e f l e c t i t s r e l a t i v e frequency. In synpolydactyly, extent of duplication varies but i s always syndactylous. Typical features of t h i s type of Polydactyly were presented-by a case (PLH) brought to the attention of the investigator but not included as a proband. The c h i l d had supernumerary proximal and medial phalanges of the fourth finger b i l a t e r a l l y without duplication of the d i s t a l phalanges. Components of the accessory d i g i t were bound by webbing to the t h i r d and fourth fingers. The mother and maternal grandmother of PLH had b i l a t e r a l syndactyly of fingers three and four; however i t i s not known i f duplicated elements of the fourth finger were included i n the web. A f a m i l i a l history of the t r a i t i s common. Occasionally with synpolydactyly the fourth and f i f t h fingers are syndactylous or there may be an association with accessory toes polysyndactylous to the fourth and f i f t h d i g i t s ( B e l l , 1953; Temtamy, 1966b), 49 G. Ulnar Polydactyly Supernumerary d i g i t s of the ulnar border only are nearly always rudimen-tary. These may consist of a wart-like projection, a fleshy skin tag or most often a pedicle which contains cartilaginous of o s s i f i e d phalangeal elements. B i l a t e r a l pedicles with bony elements are c l e a r l y i l l u s t r a t e d by X-ray i n a paper by Walker (1961). Frequently there i s a f i n g e r n a i l . Attachment i s usually by a narrow stalk of skin to the l a t e r a l border of the proximal phalanx of the f i f t h finger or the area near the head of the f i f t h metacarpal. The occurrence of a supernumerary d i g i t off the r a d i a l aspect of the f i f t h finger as i l l u s t r a t e d by Barsky (1.958) p. 53) i s quite unusual. The s i t e of attach-ment i s associated with an accessory t r i r a d i u s (see Appendix B). Occasionally i f a more completely developed accessory finger i s present there w i l l be the normal or a reduced number of phalanges which may a r t i c u l a t e with a broad or b i f i d f i f t h metacarpal or an accessory s i x t h metacarpal. Cummins (1932) discussed accessory ulnar d i g i t s , giving meticulous attention to t h e i r morphology. He c l a s s i f i e d supernumerary f i f t h fingers primarily by the degree of proximal constriction, pointing out however i n ac t u a l i t y there i s a gradation from the most poorly di f f e r e n t i a t e d appendage suspended by a thread of skin to the perfectly formed, functional finger. I t was stressed that most accessory ulnar d i g i t s are small with signs of inhibited growth and d i f f e r e n t i a t i o n , and these rudimentary d i g i t s were referred to as postminimi. I t was noted cartilage never extended into the basal region of the postminimus, a single small phalanx was often present, and bone formation was retarded or nonexistant. Cummins assumed that the stalk was the region where growth was most i n h i b i t e d , and with the rest of the d i g i t growing more rapidly, a pedicle formed. Danforth (1919) suggested that- early i n development an accessory ulnar d i g i t was si m i l a r to the other fingers. However i n most cases differentiation did not proceed synchronously with the other d i g i t s and the accessory tended to become constricted off. I t was postulated that i n certain cases spontaneous amputation or sloughing off of pedunculated postminimi occurred (streeter, 1930). At b i r t h a l l that remains of the accessory d i g i t i s a "pointed st a l k " or "nodular elevation" associated with a t r i r a d i u s . Findings i n cases of Cummins (1932) and Temtamy (1966b)) have also been interpreted to be indicat i v e of spon-taneous amputation. Cummins further speculated that amputation might occur s u f f i c i e n t l y early i n the development of the fetus that a l l evidence of the . s i t e of attachment be obliterated due to reorganization and growth. Simpkiss and Lowe (1961) found 2U infants with supernumerary d i g i t s of the ulnar border only (H11 u n i l a t e r a l , 16 b i l a t e r a l ) among 2,068 Negro newborns, an incidence of 1:3.tl> per 1,000.. The accessory f i f t h d i g i t was described as rudimentary, most often with a single phalanx, and sometimes a f i n g e r n a i l . Attachment of the extra d i g i t was commonly by skin alone and i n each case to the proximal phalanx of the f i f t h finger. An additional case had u n i l a t e r a l ulnar and f i b u l a r Polydactyly. From the data of Farabee (1903) i n Table XI I I i t can be seen that f i b u l a r Polydactyly i s more commonly seen i n association with ulnar accessory d i g i t s than t i b i a l or r a d i a l . H. Fibular Polydactyly Polydactyly of the f i b u l a r border takes the form of an independent accessory d i g i t , a polysyndactylous accessory d i g i t , or less frequently a pedicle. The accessory toe i s usually l a t e r a l , sometimes immediately medial to the f i f t h (Gates, 1946). Occasionally i n cases where the accessory i s considered medial i t i s impossible to t e l l whether the toe i s not a duplica-t i o n of the fourth rather than the f i f t h d i g i t as an accessory metatarsal element may show an equal or greater association with the fourth metatarsal. Less frequently there i s duplication of the t h i r d toe (proband number 110). 51 Table XIII. Frequency of Accessory Digits i n Conjunction with Ulnar Polydactyly Affected border EFo. of cases ulnar duplication only R ulnar 15 L ulnar 13 B ulnar 93 ulnar and f i b u l a r duplication L ulnar, L f i b u l a r 1 L ulnar, R f i b u l a r 3 L ulnar, B f i b u l a r 4 R ulnar, R f i b u l a r 5 B ulnar, R f i b u l a r 8 B ulnar, B f i b u l a r 93 ulnar and t i b i a l duplication ? ulnar, ? t i b i a l 13 ulnar and r a d i a l duplication B ulnar, B r a d i a l 7 ulnar, r a d i a l and t i b i a l duplication B ulnar, R r a d i a l , B t i b i a l 4 ulnar duplication, no other details ? ulnar 231 t o t a l 490 Source: Farabee (1903) 52 An accessory f i b u l a r d i g i t syndactylous to the fourth and f i f t h toes has been considered a d i s t i n c t anomaly, synpolydactyly, which may associate with poly-syndactylous duplication of the t h i r d finger ( B e l l , 1953; Temtamy, 1966b). In families with f i b u l a r synpolydactyly, duplication does not occur i n individuals with nonsyndactylous fourth and f i f t h toes, and other toes may be syndactylous as w e l l . The review of Farabee (1903) l i s t e d 21 b i l a t e r a l and 14 u n i l a t e r a l (7L,7R) f i b u l a r cases. Egawa et a l . (1969) studied 16 cases (11R, 3L, 2B). These findings suggest duplication i s more commonly u n i l a t e r a l among cases with accessory d i g i t s of the f i b u l a r border only. One of the 16 cases had b i l a t e r a l ulnar Polydactyly with syndactyly of fingers three and four ( l e f t ) . This was most l i k e l y associated with b i l a t e r a l f i b u l a r Polydactyly (? synpolydactyly) since Farabee found among uln a r - f i b u l a r cases 97 with b i l a t e r a l and 17 with, u n i l a t e r a l f i b u l a r duplication. Fibular accessory d i g i t s commonly occur with ulnar duplication but rare l y with t i b i a l or r a d i a l duplication. Egawa e t . a l . (1969) included descriptive d e t a i l s and photographs of the forms of duplication presented by t h e i r 16 cases. Most cases were noted to be l a t e r a l , however there was one with b i l a t e r a l duplication of the d i s t a l phalanx, fourth toes. Syndactyly joined the accessory to the f i f t h toes (13), to the fourth toes ( l ) , and i n at least two cases involved the fourth, f i f t h and supernumerary d i g i t s (? synpolydactyly). In only two cases were there independent accessory toes. The authors concluded that syndactyly was charac-t e r i s t i c of Polydactyly of the foot asx t h e i r t i b i a l case and most f i b u l a r cases were polysyndactylous. Gates (1946) noted that more complete forms of f i b u l a r Polydactyly have a greater tendency to be syndactylous. Considerable v a r i a t i o n i n the point of b i f u r c a t i o n was found by Egawa et a l . (1969): distal phalanx (1 B), PIP j o i n t (5 U), proximal phalanx (2 U, t B), MP j o i n t (3 U), metatarsal (1 U) and uncertain (3 U, I B ) . 53 Egawa et a l . (1969) were studying cases referred for assessment and corrective surgery. Although i t i s not possible to estimate the r e l a t i v e frequency of polysyndactylous accessory d i g i t s i n r e l a t i o n to other forms of postaxial supernumerary toes, p a r t i c u l a r l y pedicles, the data suggest poly-' syndactylous supernumerary d i g i t s are the p r i n c i p a l non-pedicle form of fibular Polydactyly among Japanese people. Findings of Neel (1958) would appear to support t h i s as well (see p. 39). I. Ulnar-fibular Polydactyly The presence of ulnar and f i b u l a r duplication has often been noted i n the same i n d i v i d u a l , but has not previously been considered a d i s t i n c t form of postaxial Polydactyly. In this study the simultaneous occurrence of ulnar and f i b u l a r accessory d i g i t s w i l l be referred to as u l n a r - f i b u l a r Polydactyly. Individuals with both ulnar and f i b u l a r duplication and individuals with ulnar (or f i b u l a r ) accessory d i g i t s who have a family history of f i b u l a r (or ulnar) duplication are postulated to have the u l n a r - f i b u l a r type of Polydactyly. Expression of u l n a r - f i b u l a r Polydactyly would be expected to be variable. C h a r a c t e r i s t i c a l l y polydactylous feet present well-formed accessory f i f t h toes whereas accessory ulnar d i g i t s range from very rudimentary to f u l l y -formed. Children of parents with u l n a r - f i b u l a r duplication may present ulnar, f i b u l a r or ulnar and f i b u l a r accessory d i g i t s ; conversely parents who express only the f i b u l a r or presumably the ulnar component may have children with ulnar and/or f i b u l a r accessory d i g i t s . I t seems highly u n l i k e l y a family with several affected individuals would express only the ulnar or only the f i b u l a r component. D i f f e r e n t i a t i o n of such a family from one with ulnar Polydactyly or with f i b u l a r Polydactyly could be suggested by morphology of the accessory d i g i t s and the pattern of inheritance (see results and discussion i n t h i s section and the section on genetics). 54 J . Polysyndactyly Polysyndactyly has been c l a s s i f i e d as a d i s t i n c t type of Polydactyly (Temtamy, 1966b)and i s of p a r t i c u l a r interest because affected individuals i n some families have postaxial i n addition to preaxial supernumerary d i g i t s . Preaxial malformation i s probably always present whereas expression of postaxial components i s more variable. The feet are more severely affected than the hands. P a r t i a l or complete duplication of toes one or two i s c h a r a c t e r i s t i c ; there may be shortening of the f i r s t metatarsal and l a t e r a l ( t i b i a l ) deviation to a hallux varus deformity. A l l the toes are syndactylous with toes two and three to the greatest extent. Sometimes a supernumerary f i b u l a r toe i s present as w e l l , usually i n the form of a pedicle or independent accessory d i g i t . In the hands thumbs may be spadelike, broad, b i f i d or present l a t e r a l (radial) deviation of the d i s t a l phalanx. Fingers three and four are syndactylous to a variable extent, and i n some cases there i s a pedicle-type accessory ulnar d i g i t . With polysyndactyly, i n contrast to synpolydactyly, syndactyly i s not seen i n the absence of Polydactyly (Temtamy, 1966b). K. Results Various types of Polydactyly were presented by the 138 probands, as shown i n Table XIV. Duplication of fingers (88/137*, 64 fo) occurs more frequently than duplication of toes (33/137, 24 f ) or fingers and toes (16/137, 12 fo). Most cases (135) have a single supernumerary d i g i t per limb; two exceptions have seven d i g i t s on one limb. Duplication i s u n i l a t e r a l i n 80 cases (58 fo), b i l a t e r a l i n 52 (38 fo) and i n cases with Polydactyly of the hands and feet sometimes a combination of both: b i l a t e r a l ulnar and u n i l a t e r a l f i b u l a r Poly-dactyly (3), u n i l a t e r a l ulnar and b i l a t e r a l f i b u l a r Polydactyly (2). An extra d i g i t on one limb may be more rudimentary than that on another. *137 since description of supernumerary d i g i t ( s ) was unavailable f o r one case 55 Table XIV. Site of Duplication According to Sex of the Probands Preaxial Postaxial  S i t e of duplication males females t o t a l males females t o t a l L hand R hand B hands L foot R foot B feet L**& R feet R hand, R foot B hands, B feet B hands, L foot B hands, R foot R**& L hands, R foot L hand, B feet R hand, B feet L hand R hand B hands R foot B feet unknown 9 12 1 . 2 2 3 '5 " 1 * 12 17 2 2 4 Border Unknown 1 •1 1 2 1 1 1 1 1 2 1 14 5 18 7 2 7 1 2 6 1 3 1 1 23 5 26 9 8 6 1 1 10 1 1 1 1 1 *triphalangeal supernumerary thumb R; triphalangeal thumb l e f t **two supernumerary d i g i t s on limb preceding symbol 56 Supernumerary d i g i t s are located preaxial (37) or postaxial (94) on the hands and/or feet; i n seven cases the affected border i s unknown. None of the probands have both postaxial and preaxial duplication, however one sib (family number 85) has t i b i a l and ulnar Polydactyly and more distant r e l a t i v e s of probands with ulnar Polydactyly are known to have duplicated f i r s t toes (families numbers 84, 85, 115) and thumbs (families numbers 86, possibly 85 and 88). Site of duplication according to sex i s also given i n Table XIV.' The overall figures of 63 males to 31 females for postaxial duplication and 26 males to 11 females for preaxial duplication mask a number of p e c u l i a r i t i e s . U n i l a t e r a l duplication (46 postaxial : 31 preaxial : 3 unknown) accounts for approximately 50 % (46/94) of the postaxial cases compared to 84 % (31/37) of the preaxial cases. Most of the u n i l a t e r a l preaxial cases involve thumb Polydactyly (29/31, 94 ft), while duplication of the f i f t h finger affects 61 % of the postaxial cases (28/46). The r a t i o of males to females with u n i l a t e r a l Polydactyly of the hands i s sim i l a r for the ulnar (19 males : 9 females) and r a d i a l (21 males:: 8 females) borders, a r a t i o of 2.1 : 1 and 2.6 : 1 respectively. Among u n i l a t e r a l preaxial cases there are s l i g h t l y more with r i g h t duplication (17 R, 12 L) whereas among u n i l a t e r a l ulnar cases there are few with the right side affected (23 L, 5 R). These f i v e are males; the only female with r i g h t ulnar Polydactyly has righ t f i b u l a r duplication as w e l l . Among u n i l a t e r a l cases of the preaxial and of the postaxial borders, tibial duplication i s infrequent (2/31) i n contrast to duplication exclusively f i b u l a r (17/46). The number of f i b u l a r cases according to sex with r i g h t duplication (2 males : 6 females) i s roughly the opposite of the number with l e f t duplica-t i o n (7 males : 2 females). This finding becomes even more pronounced when cases with both ulnar and f i b u l a r Polydactyly are also considered. Pour cases have u n i l a t e r a l f i b u l a r Polydactyly (RP, 3 females; LP, 1 male). Including these makes a t o t a l of two males and nine females with r i g h t duplication and eight males and two females' with l e f t duplication. This tendency for females to present ri g h t f i b u l a r Polydactyly and males l e f t i s i n contrast to ulnar Polydactyly. B i l a t e r a l Polydactyly (6 preaxial : A3 postaxial : 3 unknown) i s less frequent among the probands than u n i l a t e r a l . Preaxial cases are r a d i a l (1 male, 1 female), one with a supernumerary triphalangeal thumb righ t and a single triphalangeal thumb l e f t , or t i b i a l (2 males, 2 females). No cases have both r a d i a l and t i b i a l duplication. B i l a t e r a l postaxial Polydactyly i s more commonly ulnar (26) than f i b u l a r (7) or ul n a r - f i b u l a r (10). A r a t i o of approximately two males to one female i s seen with ulnar and with ulnar-f i b u l a r Polydactyly. The seven cases with b i l a t e r a l f i b u l a r duplication are males. I f the two cases with b i l a t e r a l f i b u l a r and u n i l a t e r a l ulnar Polydactyly are added as w e l l , there i s a t o t a l of nine males with b i l a t e r a l f i b u l a r d u p l i -cation. In addition both cases of b i l a t e r a l Polydactyly of the feet, border unknown, are males. Table XV describes the forms of duplication observed i n the probands. Rudimentary d i g i t s recorded i n medical records as skin tags or pedicles, or noted to have been t i e d off. have a l l been categorized as pedicles i n this table. Further description when available i s given i n Appendix A. Preaxial duplication tends to consist of some degree of b i f i d i t y of the normal bony elements (19), often with some degree of syndactyly between the p r i n c i p a l and the sup:ernumerary rays. Rudimentary supernumerary d i g i t s i n the form of a duplicated terminal phalanx are more characteristic than a pedicle or skin tag loosely attached to the t i b i a l or r a d i a l borders (? 7). Occasionally the supernumerary d i g i t , excluding pedicles, does not a r t i c u l a t e or connect with bony elements of the p r i n c i p a l f i r s t d i g i t (2/19). I f more information were available on three of the cases classed as pedicles, they might have been considered well-formed d i g i t s without a r t i c u l a t i o n . Of the 58 Table XV. Description of the Forms- of Duplication Presented by the Probands Number of cases t i b i a l duplication R L B Total duplic. d i s t a l phalanx - - 1 1 duplic. proximal and d i s t a l phalanges 1 - 2 3 extent of duplic. unknown 1 - 1 2 t o t a l 6 r a d i a l duplication pedicle duplic. d i s t a l phalanx b i f i d proximal phal. and duplic. d i s t a l phalanx duplic. proximal and d i s t a l phalanges p a r t i a l duplic. metacarpal, prox. and d i s t a l phal. p a r t i a l duplic. metacarpal with one duplic. phal. triphalangeal d i g i t extent of duplic. unknown ulnar duplication t o t a l 2 4 4 1 2 1 3 5 3 1 2 1* 7 7 1 4 2 2 3 5 31 pedicle or skin tag better developed d i g i t L, pedicle R well-formed d i g i t , may a r t i c u l a t e extent of duplic. unknown f i b u l a r duplication t o t a l 1 4 20 1 2 3 41 1 3 9 54 pedicle - 2 - 2 well-formed d i g i t R, pedicle L - - 1 1 d i g i t syndactylous with 5th 1(57) or 4th ( 1 ) : l a t e r a l to 3 3 2 8 5th ( 3 ) , unknown ( l ) , medial ( 3 ) , medial L & l a t . R ( l ) well-formed d i g i t : l a t . to 5th ( l ) , medial ( 4 ) , unk. ( 7 ) 6 3 3 12 well-formed d i g i t l a t e r a l to 5th B; 7th d i g i t inserted - 1 between toes 3 - 4 L t o t a l 24 u l n a r - f i b u l a r duplication pedicles: B or U ulnar and B or U f i b u l a r - 3 at least one well-formed d i g i t - - - 4 4 d i g i t l a t e r a l to 5th finger B; 7th finger• inserted - - - 1 between 3 - 4 R; acces. d i g i t R f i b u l a r well-formed d i g i t , may a r t i c u l a t e : B or U ulnar and - - - 6 B f i b u l a r extent of duplic. unknown .. - - - 2 t o t a l 16 border unknown hand ' 1 1 1 3 foot 1 - 2 3 Polydactyly - - - 1 t o t a l 7 ^triphalangeal supernumerary thumb R; triphalangeal thumb L 59' seven cases categorized as pedicles, a l l are -unilateral r a d i a l . This could suggest that pedicles r a r e l y occur on the t i b i a l border or simply r e f l e c t the fact that r a d i a l duplication (31 ) occurs more frequently than t i b i a l (6). In addition i t should be noted that among cases with pedicle Polydactyly the l e f t side i s more commonly affected (5/7), whereas the more complete forms of pre-a x i a l duplication occur most often on the right side ( 9 / l l ) . Three cases of polydactylous thumb involve a supernumerary triphalangeal thumb (2R, 1L). S ince i n one of these cases there i s a supernumerary phalanx of the l e f t thumb as w e l l , i t i s classed as b i l a t e r a l r a d i a l duplication. Duplication consisting of a triphalangeal and/or supernumerary triphalangeal thumb i s more commonly b i l a t e r a l (2U, 1B) than i s duplication involving a uni-or biphalangeal thumb (22U, 1 B). Such a statement may be true only of r a d i a l Polydactyly rather than, preaxial Polydactyly i n general. Among the probands . duplication of the f i r s t toe i s more frequently b i l a t e r a l (4/6). Three cases of t i b i a l Polydactyly have f a i r l y complete duplication and a l l three are males. A tendency for males to present a greater degree of duplication i s not seen with r a d i a l Polydactyly where there appears to be no difference i n extent of duplication according to sex of the proband. Ulnar Polydactyly (54) most often takes the form of skin tags or pedicles which occur commonly on the l e f t hand (18) or b i l a t e r a l (20) and infrequently on the righ t (3). These pedicles usually arise from the l a t e r a l side of the f i f t h finger i n the mid-region of the proximal phalanx, towards i t s base, or s l i g h t l y lower near the head of the f i f t h metacarpal. Some extra d i g i t s have f i n g e r n a i l s . Descriptions seldom mention the presence of bony tissue (7), and i n only two cases was the accessory d i g i t noted to a r t i c u l a t e with the f i f t h metacarpal. Well-formed fingers (10) which may a r t i c u l a t e (5/10) are seen more often i n conjunction with f i b u l a r Polydactyly. 60 Postaxial supernumerary toes tend to be f a i r l y well formed (21 / 24) and i n only three cases are the extra d i g i t s described as pedicles. One of these cases has a well-formed supernumerary toe on the l e f t and a pedicle on the ri g h t foot. In 15 cases the extra d i g i t appears as a duplication of the f i f t h toe situated l a t e r a l or medial to the p r i n c i p a l toe, or i n one case l a t e r a l on the ri g h t and medial on the l e f t . I f the f i f t h and supernumerary are equally well formed i t may be d i f f i c u l t to decide which i s accessory. In additional cases accessory toes inserted between the fourth and f i f t h show a p a r t i a l attachment to both the fourth and f i f t h d i g i t s ( l ) . or are more closely associated with the fourth ( i i ) , which may represent an excess of material pertaining to anlagen of the normal fourth d i g i t . Insertion between the t h i r d and fourth toes occurs as well ( l ) . The proband with t h i s duplica-t i o n was also noted to have a seventh d i g i t l a t e r a l to the normal f i f t h toe. Insertion of a supernumerary ray between d i g i t s three and four may be common when there are two accessory postaxial d i g i t s on a limb, for this pattern of duplication i s also present i n a case of ul n a r - f i b u l a r Polydactyly which has two postaxial accessory fingers on the r i g h t hand. Syndactyly of the supernumerary with the fourth toe (1) or with the f i f t h toe ( 4 ) , or of the supernumerary, fourth and f i f t h toes (3) i s f a i r l y common ( 8 / 2 4 ) . I t should also be noted that i n cases with exclusively f i b u l a r Poly-dactyly, toes described with a rudimentary metatarsal element l i e medial to the f i f t h ( 5 / 5 ) , the extra metatarsal inserted between the fourth and f i f t h or the t h i r d and fourth metatarsals. Among cases with u l n a r - f i b u l a r Polydactyly there i s fusion of extra metatarsal elements with the f i f t h (4/4)* the l a t e r a l d i g i t being supernumerary i n at least one case. This finding may be of li m i t e d significance and resul t from inadequate descriptions. For at least two cases with u l n a r - f i b u l a r Polydactyly have extra toes located medial to the f i f t h but de t a i l s regarding metatarsal elements or a r t i c u l a t i o n were unavailable. 61 As previously noted, fibular duplication among males tends to be l e f t or bilat e r a l whereas females tend to have right Polydactyly. The extra toe of over half of the females ( 5 / 8 ) is immediately medial to the f i f t h , which i s five of the six unilateral cases described with this form of duplication. Cases with ulnar-fibular Polydactyly tend to have more complete forms of duplication. Supernumerary digits limited to pedicle forms are described in only three cases; i n others(11) there i s at least one (2/ll) or more (9/ll) well-formed extra fingers or toes. Fingers are more rudimentary i n five cases toes i n one. Extra toes are located medial to the f i f t h (1 male, 1 female) and lateral (2 males). Fibular polysyndactylous accessory digits appear to be more characteristic of Polydactyly affecting the feet alone, for only one case was noted to have minimal syndactyly of the f i f t h with the supernumerary. Probands with the most completely formed extra fingers and toes (6) are males, whereas females with ulnar-fibular Polydactyly tend to have somewhat rudimen-tary extra digits on one or more limbs. In calculating the incidence of each type of Polydactyly, given i n Table XVI, cases with multiple congenital anomalies have been grouped separately. One case of ulnar Polydactyly and two cases of fibular Polydactyly have been included among cases with ulnar-fibular duplication due to the presence of ulnar and fibular. Polydactyly i n the family of each of these probands. L. Discussion It i s interesting to compare•the B.C. findings with those of Tan (1969) on a newborn population composed primarily of Chinese, Malay and [East] Indian babies. The incidence of Polydactyly i s nearly identical: 1.15 (Singapore.) compared to 1.02 (B.C.). The types of duplication found by Tan are br i e f l y outlined i n Table XVII. As observed i n B.C., duplication of fingers is more common (67 $>'-. 64 i° B.C.) than duplication of toes (26 fo : 24 % B.C.) or finge 62 Table XVI. Incidence of S p e c i f i c Types of Polydactyly i n B r i t i s h Columbia Cases without Incidence per 1,000 multiple major anomalies Ho. of cases l i v e b o r n i n f a n t s r a d i a l d u p l i c a t i o n . biphalangeal 24 0.18 triphalangeal 3 0.02 t i b i a l d u p l i c a t i o n 6 0.04 pr e a x i a l d u p l i c a t i o n 0.24 ulnar d u p l i c a t i o n * 43 0.32 f i b u l a r d u p l i c a t i o n * * 20) 0.15 u l n a r - f i b u l a r d u p l i c a t i o n 12 0.08 po s t a x i a l d u p l i c a t i o n 0.55 polysyndactyly 1 0.01 s i t e of d u p l i c a t i o n unknown 5 0.04 cases without multiple 114 0.84 major anomalies Cases with multiple major anomalies  a l l types of d u p l i c a t i o n 24 . 0 . 1 8 t o t a l 138 1.02 *case number 86 included among u l n a r - f i b u l a r cases **cases numbers 93 and 110 included among•ulnar-fibular cases 63 Table XVII. Types of Polydactyly Pound i n Singapore S i t e P r e a x i a l R L I Po s t a x i a l R B Total hands feet hands & feet 18 5 3 -1 1 2 5 B ulnar, B f i b u l a r , L r a d i a l B ulnar, B f i b u l a r 28 11 1 2 t o t a l 42 Note: Incidence of Polydactyly per 1 ,000 l i v e b i r t h s was 42/36,427 or 1 . 1 p. Source:- Tan, 1969 64 and toes (l fo : 12 $ B. C.). However there i s a s t r i k i n g difference between the Singapore and the B.C. populations regarding,affected border of the limbs. The frequency of preaxial duplication i n the Singapore population (68 fo) i s nearly equal to the frequency of postaxial duplication i n B.C. (71 i°) • .Among cases with polydactylous hands Tan found r a d i a l duplication (90 % : 38 fo B.C.) more frequent than ulnar. Polydactyly of the thumb was most often u n i l a t e r a l (23/25) , a greater proportion with ri g h t duplication (18/23) than i n the B.C. study. The number of cases with b i f i d f i r s t metacarpal (4) and duplicated proximal phalanx a r t i c u l a t i n g with the f i r s t metacarpal (8) was nearly as great as that with b i f i d proximal (3) and b i f i d or duplicated d i s t a l phalanges (4) and pedicles ( 6 ) . In one case the duplicated thumb was t r i p h a -langeal. Polydactyly on the r a d i a l border tended to be a more complete form of duplication among Singapore probands than among B.C. probands. This i s also observed when the 13 cases reported by Handforth (1951) are compared with the B.C. probands. The paucity of ulnar duplication (3/28) i n Tan's study i s further exaggerated by the fact that i n one case the Polydactyly can be attributed to inheritance of E l l i s - v a n Creveld syndrome. The r e l a t i v e frequency of r a d i a l Polydactyly i n the Singapore population compared to B. C. (2 .6 : l ) . i s increased to a greater extent than that of t i b i a l (1 .7 : 1 ) . Duplication of the f i r s t toe does not comprise a s i g n i f i c a n t l y greater proportion of cases with supernumerary toes i n Tan's study (27 %) than i n the B.C. study (20 % ) . Bony attachment was present i n two t i b i a l cases (2 R) whereas the supernumerary consisted of a pedicle i n the t h i r d case (1 R). Finding the right side affected i n these cases strengthens the impression gained from the B.C. study that right duplication i s more common on the t i b i a l and r a d i a l borders. Tan found the l e f t side more frequently affected among cases with f i b u l a r Polydactyly ( 5 / 8 ) . Pedicles (3) were seen as well as a r t i c u l a t i n g supermini-65 erary toes ( 5 ) . One case had syndactyly of toes four.and f i v e , but i t was not noted whether the supernumerary was included i n the web or l a t e r a l to i t . No information regarding the sex of probands was given so i t i s unknown whether males had predominantly l e f t or b i l a t e r a l duplication and females right as found i n B.C. One additional thing to note from the Singapore study i s the presence of thumb Polydactyly (L) i n one of the cases with b i l a t e r a l ulnar and b i l a t e r a l f i b u l a r Polydactyly (3) . The most frequent form of Polydactyly observed by Simpkiss and Lowe (1961) among Negro newborns i s the type presented'^most often by the B.C. probands. In Kampala 27 out of 29 infants had a rudimentary accessory ulnar d i g i t (11 U, 16B) whereas u n i l a t e r a l ulnar and f i b u l a r and b i l a t e r a l f i b u l a r Polydactyly were each seen i n one c h i l d . The extreme preponderance of ulnar Polydactyly among the Negro infants (90 fo) contrasts with the B.C. findings (39 %) and those of Tan (if). Regarding Polydactyly of the foot, findings i n the B.C. study can.be compared with the patients reported by Egawa et a l . (1969). The 15 l a t e r a l f i b u l a r cases consisted of eight males (1B, 5R, 2L) and seven females (6R, 1L). Among u n i l a t e r a l cases, males as well as females, the rig h t foot was more commonly affected (Egawa, 1971) whereas the majority of rig h t u n i l a t e r a l cases i n the B.C. study are females. 66 V I I . Genetics A. Introduction A number of hypotheses regarding the nature and etiology of Polydactyly have been presented i n the past. The concept that supernumerary d i g i t s could be caused by maternal impressions i s no longer accepted. Also discarded i s the theory a t t r i b u t i n g accessory d i g i t s as b a s i c a l l y an a t a v i s t i c phenomenon (Albrecht, 1886). Ahl f e l d (1880) believed Polydactyly resulted from i n t r a -uterine i n j u r i e s . The role of environmental agents i n the etiology of super-numerary d i g i t s i n man i s e s s e n t i a l l y unknown. Lenz (1964) noted polydactylous thumbs i n infants with a history of maternal ingestion of thalidomide around day 34 after the l a s t menstrual period; triphalangeal thumbs were associated with ingestion around day 48 to 50. In thalidomide pathogenesis accessory d i g i t s were always preaxial and duplication of f i r s t toes more common than duplicated thumbs. A syndrome of 'diabetic embryopathy" has also been described i n which aplasia or hypoplasia of the femurs, cardiac and renal malformations, Polydactyly of the feet, and abnormalities of the coccyx occur (Kucera et a l . , 1965). Weismann (1893) postulated that Polydactyly resulted from v a r i a t i o n i n the germ plasm. The genetic component i n the embryogenesis of supernumerary d i g i t s has received the greatest attention i n the past; and dominant, recessive and polygenic modes of inheritance have- been, suggested for various types and forms of duplication. A review of these hypotheses i s given i n t h i s section. Postaxial and preaxial duplication are considered separately since with the exception of polysyndactyly they are generally thought to result from different gene mutations, ftieir simultaneous occurrence coincidental (Sverdrup, 1922; Gates, 1946; Temtamy, 1966b.i; Woolf & Woolf,- 1970% Discussion and specula-t i o n follow presentation of the results of the B.C. study. 67 B. Literature review The e a r l i e s t report of the f a m i l i a l nature of Polydactyly which J u l i a B e l l (1930) was able to locate concerned the two affected daughters of C. Horatius, who were mentioned i n the writings, of P l i n y . Accounts of populations i n which nearly a l l the individuals were polydactylous include the reports of Megasthenes who described an eight-toed race of men (Pliny, cited by B e l l , 1930), Lucker (1924) who recorded Polydactyly and harelip to be endemic i n a secluded German v i l l a g e , and De Linares (1930) whose account concerned a small v i l l a g e i n Spain. Several references (Boinet, 1898; Devay, 1863; Ballowitz, 1904) may refer to the same isolated v i l l a g e in'the Departement d'Isere, noted to have many polydactylous individuals with s i x d i g i t s on a limb. The t r a i t was attributed to intermarriage and i s said to have disappeared when marriages to normal individuals became common. This would be incompatible with dominant inheritance (Odrione, 1943), was inexplicable, and some writers proclaimed i t a hoax. However Daisy Bates (1966) related a s i m i l a r story regarding a group of Australian aborigines. And the family from Bukowina reported by Shevkenek and Thompson (1933) tends to further support the v a l i d i t y of such accounts. In the kinship of Shevkenek and Thompson (1933) i t was concluded postaxial Polydactyly was inherited as a simple autosomal recessive. Recessive i n h e r i -tance was postulated for the Negro family investigated by Snyder (1929), and i t i s interesting to note that a l l ten offspring (5 males., 5 females) from the marriage of two polydactylous individuals were affected. In addition, pedigrees of B e l l (1930), Salzano (1961 ) and Mohan (1969) are also compatible with a recessive mode of inheritance. Polydactyly appeared to be a recessive character i n the sibs reported by Oliver (1940) but was associated with mental deficiency and physical weakness. These cases are considered to represent a recessive syndrome. Other recessive syndromes with a high incidence of 68 postaxial Polydactyly are Laurence-Moon-Biedl syndrome (see p.118) and E l l i s -van Creveld syndrome (Smith, 1 970) . Gates (1946) accepted the existence of recessive Polydactyly (postaxial), considered i t very rare i n comparison with the dominant form, and f e l t i t was expressed by a mild extent of duplication. He points out however that a dom-inant character with low penetrance would be indistinguishable from a reces-sive. The World Health Organization study (Stevenson et a l . , 1966) found no increased frequency of consanguinity among the parents of polydactylous children which suggests recessive inheritance accounts for a l i m i t e d percentage, i f any, of the cases of Polydactyly unassociated with multiple congenital anomalies. The term i r r e g u l a r dominant inheritance was used to explain instances where an i n d i v i d u a l assumed to have transmitted Polydactyly f a i l e d to express i t (Brandeis, 1915). There are many examples of t h i s i n family h i s t o r i e s of postaxial Polydactyly (Sedgwick, 1863; Brandeis, 1915; B e l l , 1930; Jackson, 1937; Caiman, 1942; Odrione, 1943; Pipkin & Pipkin, 1946; Walker, 1961; Mohan, 1969;' Woolf & Woolf, 1970). Gates (1946) f e l t i r r e g u l a r dominance was a simpler explanation for the kinship reported by Snyder (1929) than recessive inheritance. The elusive nature of i r r e g u l a r dominance i s i n contrast with pedigrees exhibiting more conventional dominant inheritance ( C a r l i s l e , 1814; Sverdrup, 1922; Dehus & Snyder, 1932; Barrer, 1947; Johnston & Davis, 1953; De Marinis & Sobbota, 1957; Woolf & Woolf, 1970). The family reported by De Marinis & Sobbota (1957) i s of special note due to the fact that both parents had b i l a t e r a l ulnar and f i b u l a r Polydactyly and only one of t h e i r three daughters was affected. Barrer (1947) on the other hand saw a family i n which both parents had l e f t ulnar duplication and t h e i r s i x children were s i m i l a r l y affected. The chances were estimated to be 91 out of 100 that at least one of the sibs was homozygous. Thus the extent of duplication expressed 69 by the homozygote must be indistinguishable from that.of the heterozygote. f o r the type of ulnar Polydactyly presented by that family. Hypotheses were advanced to account for i r r e g u l a r dominant inheritance and sporadic occurrences of postaxial Polydactyly. Bateson ("1909) postulated Polydactyly was due to dominant factors which could be i n h i b i t e d or suppressed by other factors. In 1922 i t was suggested that a r t i c u l a t i n g accessory ulnar d i g i t s resulted from the operation of cumulative factors whereas less w e l l -developed accessory f i f t h fingers were due to one Mendelian factor whose action could be suppressed•by other factors (Sverdrup, 1922). Examination of the Snyder (1929) pedigree prompted Gates (1946) to remark that expression of Poly-dactyly might require two "gene" doses i n some families but only a single dose i n others. In the l a t t e r instance penetrance would probably be low. Pipkin and Pipkin (1 946) postulated expression might'depend on the i n t e r -action of modifying genes with a single main dominant gene or, as a simpler explanation, depend on two dominant genes, one a rare gene i n the population and the other f a i r l y common. Development of accessory postaxial d i g i t s would resul t from the cooperative action of the two genes. The two-gene hypothesis was adopted by Walker (196'1) who designated the genes responsible P and A. The frequency of P was to be low whereas A would have a moderately high frequency. Individuals of genotype PpAA and PpAa would be polydactylous • and the phenotype corresponding to Ppaa would be normal. The p o s s i b i l i t y was raised that the accessory gene might be associated with another anomaly (Pipkin & Pipkin, 1946), or might be detectable only i n the presence of the dominant Polydactyly gene (Walker, 1961 ). I t has also been postulated postaxial duplication may be determined by more than two l o c i , possibly with genes of "major effect" and genes of "minor effect" both operating (Mohan, 1969). Such a system would f a l l into the realm of polygenic inheritance. 70 V a r i a b i l i t y i n expression of postaxial Polydactyly has evoked nearly as much speculation as nonpenetrance. Although accessory d i g i t s had been c l a s s i f i e d on the basis of morphology before 1922 (Annandale, 1865), i t was the pedigree of Sverdrup (1922) which suggested a genetic difference existed between two morphologically d i s t i n c t forms of duplication which were designated type A and type B. Type A Polydactyly referred to an accessory ulnar d i g i t a r t i c u l a -t i n g with the f i f t h metacarpal or an extra metacarpal and which often gave the impression of an extra finger inserted between fingers four and f i v e . Sverdrup f e l t these probably represented a b i f u r c a t i o n of the f i f t h finger. Type B accessory f i f t h fingers had no bony connection with the ulnar border of the hand but might contain o s s i f i e d elements. This form of duplication may be described as a pedicle or skin tag. One perplexing thing was accessory f i f t h toes were equally well developed among individuals with type A as individuals with type B ulnar duplication. Among offspring of A type individuals Sverdrup found an excess of affected children with type A or type B duplication. The r a t i o of affected to normal children of B type individuals was less than or equal to one, and i t was postulated ulnar duplication would be limited to type B Polydactyly. Although the hypothesis i s not e n t i r e l y satisfactory i t has often been referred to i n the l i t e r a t u r e . The family on which i t was based has a couple of inconsistencies i n the type of Polydactyly expressed; kindred 7 of Woolf and Woolf (1970) and family number 127 of the B.C. study are c l e a r l y exceptions. I t can be questioned whether two genetically d i s t i n c t types of Polydactyly are segregating i n Sverdrup's pedigree, the kindred 7 of Woolf and Woolf (1970) and s i m i l a r f a m i l i e s . V a r i a b i l i t y could result from one gene (two genes i f -postulating a two-gene system) which i s greatly influenced by the genetic milieu and environmental factors (Odrione, 194-3; Mohan, 1969). Another possible explanation considers v a r i a b i l i t y of expression to be cha r a c t e r i s t i c of the 71 main gene(s) i t s e l f due to a naturally unstable time of action r e l a t i v e to c r i t i c a l events instead of the r e s u l t of modifying genes which a l t e r the time or rate of action of the main gene(s) (Callan, 1942). Regardless of whether the pedigree of Sverdrup (1922) demonstrated i t , the existence of a genetically d i s t i n c t , consistently rudimentary type of ulnar Polydactyly (type B) as postulated i s supported by published pedigrees (Johnston & Davis, 1953; Walker, 1961) as well as the B.C. r e s u l t s . The findings of Simpkiss and Lowe (1961 ) would indicate f i b u l a r duplication i s not l i k e l y to occur with i t . Another d i s t i n c t e n t i t y among cases of postaxial Polydactyly appears to be synpolydactyly which has been noted to have an auto-somal ' dominant mode of inheritance ( B e l l , 1930; Temtamy, 1966TD)L Two types of duplication have been recognized among cases of thumb Poly-dactyly. In families with triphalangeal duplication, autosomal dominant i n -heritance with f a i r l y high penetrance has often been seen (struthers, 1863; McKellar, 1870; Atwood & Pond, 1917; Mueller, 1936; Haas, 1939; Hefner, 1940; Ecke, 1962; Temtamy, 1966b; Woolf & Woolf, 1970). T i b i a l Polydactyly may be associated with t h i s type of duplication. I t has been postulated on the basis of r a d i o l o g i c a l and dermatoglyphic evidence (Temtamy, 1966b) that some cases with r a d i a l Polydactyly of a triphalangeal nature are actually Polydactyly of the index finger (Penhallow, 1928; Manoiloff, 1931; James & Lamb, 1963; Temtamy, 1966b). These pedigrees also suggest autosomal dominant inheritance. The forms of r a d i a l Polydactyly seen i n pedigrees with triphalangeal duplication may be extremely variable and duplication i s not necessarily of a triphalan-geal nature i n a l l affected i n d i v i d u a l s . A positive family history i s infrequent among cases with Polydactyly of a biphalangeal thumb (Temtamy, 1966b; Woolf & Woolf, 1970). Descriptions i n many published cases are inadequate to determine i f there were triphalangeal f i r s t d i g i t s (Digby, 1645; Sinha, -1918; M i l l e s , 1928; Orel, 1928; Woolf & 72 Woolf, 1970). Radial or ulnar deviation of the thumb noted i n the pedigrees of Pot't (1884), Rudert (1938) and De Marinis and Sobbota (1957) suggests t r i -phalangeal duplication. The sporadic nature of most cases of r a d i a l polydaciyfy unassociated with triphalangism i s compatible with polygenic inheritance and/or the action of teratogens (Temtamy, 1966b; Woolf & Woolf, 1970). Based on the theory (Edwards, 1960, 1969) that a polygenic t r a i t with population incidence p w i l l occur at a frequency of about the square root of p in.the sibs of propositi i f there i s 100 $ h e r i t a b i l i t y , Woolf & Woolf (1970) estimated that only about 1.4 % of the sibs of his probands would be expected to have thumb Polydactyly. In 32 r a d i a l cases there were 94 sibs, none of whom were affected. However, the occurrence of an accessory thumb i n the uncle of one proband was considered indica t i v e of polygenic inheritance. Both post- and preaxial duplication occur i n one special type of Poly-dactyly, polysyndactyly (Lenglen, 1877; P f i t z n e r , 1898; Atkinson, 1901; Thomsen, 1927; B e l l , 1930; McClintic, 1935; Goodman, 1965; Temtamy, 1966b). Family h i s t o r i e s suggest the various d i g i t a l anomalies manifested in. polysyn-dactyly are inherited as a dominant t r a i t with variable expressivity rather than chance association of determining factors for syndactyly and for post-and preaxial Polydactyly (Temtamy, 196"6b). Review of the aforementioned pedigrees suggests nonpenetrance i s uncommon, however i t can occur (proband number 78). C. Genetic family h i s t o r i e s : results Evidence suggests that i n the families of 32 of the 1:38 probands there i s another in d i v i d u a l with Polydactyly. Considering only probands for whom a genetic history has been s p e c i f i c a l l y taken there are 30 out of 89 (34 with a positive family history. A comparison of the number of cases with a posi-t i v e family history according to type of duplication presented by the proband 73 i s given i n Table XVIII. This table distinguishes cases with multiple con-genital anomalies. Probands with r a d i a l duplication whose family history appears to be positive for Polydactyly are numbers 10, 18, 19, and 2 9 . The clearest case i s number 18 where the maternal grandfather was examined and had a supernum-erary thumb reported to be i d e n t i c a l to that of the proband. The mother of proband number 29, a c h i l d with triphalangeal duplication, t o l d the public health nurse there was a history of supernumerary d i g i t s i n the family. How-ever the mother did not cho.ose to participate i n the study and additional affected individuals were not specified. I t i s l i k e l y the affected person(s) belonged to the maternal side of the family since the proband's parents were not married. In family number 10 the mother indicated the maternal grandmother had told her an infant with Polydactyly had previously been born i n the family but she did not know the exact kinship between that c h i l d and her baby. The history of case number 19 i s least clear. In a pediatric consultation i t was noted that one. of the mother's cousins had been born with a "deformed thumb", the same term used to describe the proband's r a d i a l anomaly. Thus there i s the suggestion that four out of 19 probands (21 fo) without multiple congenital anomalies for whom family information was available have a positive family history of Polydactyly. This history i s f u l l y documented for one family only (1/19, 5 f). Fourteen probands with ulnar Polydactyly have a positive family history of supernumerary d i g i t s . Probands without multiple congenital anomalies whose affected r e l a t i v e s also had ulnar duplication are numbers 4 0 , 5 5, 56, 61 , 6 7 , 74 and 9 0 . Information on the additional affected persons i n families 55 and 74 was obtained i n an interview with the probands 1 parents and could not be confirmed by examination, medical records, or.other means. 74 Table XVIII. Cases with a Positive Family History of Polydactyly Type of duplication No. of cases Families interviewed . cases without cases with mma* mma +PH Families not interviewed cases without cases with mma mma -FH +FH -PH +FH PH unk FH unk r a d i a l 31 t i b i a l 6 ulnar 54 f i b u l a r 24 u l n a r - f i b u l a r 16 unknown 7 11 5 5 15 3 17 9 3 1 *•* 4 2 2 1 1 •*•*•* 3 17 8 1 4 2 1 Note: Cases are l i s t e d according to the type of duplication presented by the proband. ^multiple major anomalies **from medical records, case number 19 ***from public health records, case number 136 75 Additional affected persons with other than ulnar Polydactyly were noted i n family 85 ( t i b i a l duplication), family 87 ( r a d i a l duplication), family 86 (ulnar and f i b u l a r , ? r a d i a l duplication) and family 78 (ulnar, t i b i a l and ? r a d i a l duplication). Family 86 i s considered an example of the variable ex-pression of u l n a r - f i b u l a r Polydactyly, one sib presenting ulnar and f i b u l a r duplication and three sibs presenting ulnar. The significance of an extra-o r d i n a r i l y wide thumb i n two family members i s d i f f i c u l t to assess and may be coincidental. There i s no history of t i b i a l Polydactyly to suggest the family presents polysyndactyly as there i s i n family 78. Probands with multiple congenital anomalies who have a s i m i l a r l y affected sib are cases numbers 43 (trisomy syndrome) and 73 (polycystic kidneys, i n t e r n a l hydrocephalus and postaxial Polydactyly syndrome). Proband 46 had trisomy syndrome. The paternal grandmother of the c h i l d has f i b u l a r d u p l i -cation; t h i s i s the only anomaly she i s known to present. A positive family history of Polydactyly was found for f i v e probands with f i b u l a r duplication. In three f a m i l i e s , numbers 99, 104 and 105, an additional affected person had f i b u l a r Polydactyly. • Supernumerary d i g i t s were polysyn-dactylous i n families 99 and 104. Information "regarding family 104 was obtained through the public health nurse and i t i s unknown whether there may have been additional affected family members. Kinship of the two affected persons i n family 105 i s f a i r l y distant, the closest common ancestor known to the proband's parents i s back four generations. The second affected person was not examined nor could the account be confirmed by additional sources. An additional affected person i s known i n family 93, a sib with ulnar duplication, placing this family among ul n a r - f i b u l a r cases. The f i f t h family, number 110, has a long history of u l n a r - f i b u l a r Polydactyly including one case which presented ulnar, f i b u l a r and t i b i a l accessory d i g i t s and the proband and one sib who have two postaxial accessory d i g i t s on a single limb. 76 Eight probands with u l n a r - f i b u l a r Polydactyly have a family history of supernumerary d i g i t s . An additional i n d i v i d u a l with f i b u l a r duplication i s known i n family 119; th i s case was mentioned i n the family interview and could not be confirmed by other sources. Additional individuals with f i b u l a r and with u l n a r - f i b u l a r duplication are known i n family 127; and there are individuals with ulnar Polydactyly i n families 120, 121, and 122. Probands with multiple congenital anomalies are: number 125, a c h i l d with giant c e l l hepatitis i n whose family there are additional affected persons; number 131, whose sib i s s i m i l a r l y affected with Laurence-Moon-Biedl syndrome; and number 124 (poly-dactyly/imperf orate anus/vertebral anomalies syndrome) whose father has ulnar-f i b u l a r duplication. D. Genetic family h i s t o r i e s : discussion The proportion of r a d i a l cases with a positive family history would appear to be within 5 to 19^, depending on the substantiation required before a history i s accepted as positive. Considering b i - and triphalangeal duplica-t i o n separately, for two out of three cases with triphalangeal thumbs there i s some family information known. Evidence suggests that accessory d i g i t s have previously occurred i n one of the two families. Among probands with biphalan-geal duplicated thumbs, i t appears that 18 % (3/17) have a positive family history. There was no family history of Polydactyly among the 24 r a d i a l cases of Tan (1969). Among ulnar cases without multiple congenital anomalies 39 % (11/28) are known to have a positive family history of Polydactyly, and 29 % (7/24) have a positive history of ulnar Polydactyly. Affected members of family number 78 are believed to present variable expression of polysyndactyly; i n th i s pedigree the anomaly appears to be inherited as a dominant t r a i t with incom-plete penetrance. I t i s possible the presence of preaxial Polydactyly i n the 77 history of cases numbers 84 and. 86 i s coincidental, however Woolf and Woolf (1970) report postaxial and preaxial Polydactyly (R radi a l ) occurring separately i n t h e i r kindred 8 and a -number of si m i l a r instances have been described (Struthers, 1863; Wilson, 1896; Attlee, 1907; Sysak, 1928; Callan, 1942; Temtamy, 1966b). Five out of 14 of the probands with supernumerary f i b u l a r d i g i t s , excluding cases with multiple congenital anomalies, have a positive family history of Polydactyly and 25 f (3/12) have a history of f i b u l a r Polydactyly. This i s i n contrast to t i b i a l duplication but si m i l a r to the findings f o r ulnar cases. None of the f i b u l a r (15) or t i b i a l (l) cases of Egawa et a l . (1969) were found to have a family history of Polydactyly. Five out of eight of the probands without multiple congenital anomalies with u l n a r - f i b u l a r Polydactyly have a family history of accessory d i g i t s . Including families 86, 93, and 110, a positive history was given for eight out of 11 families {lJ$>) i n which there.is both ulnar and f i b u l a r duplication. In only one of these families,- number 110, do affected persons nearly always present u l n a r - f i b u l a r duplication. Postaxial cases without multiple congenital anomalies which have a positive h i s t o r y comprise 42 f> (21/50) of the postaxial cases for which there i s i n f o r -mation regarding the genetic family history. For comparison, Woolf and Woolf (1970) found among surgical cases of postaxial duplication 37 fo (7/19) with a family history of accessory d i g i t s ; i n the Singapore study only one out of 11 postaxial cases (9 f ) had a positive family history (Tan, 1969). I t i s i n t e r -esting to speculate whether these figures might r e f l e c t a basic difference i n p r i n c i p a l factors underlying etiology of postaxial cases i n a predominantly Caucasian population compared with a predominantly Chinese population. 78 E. Penetrance: results and discussion Review of the genetic h i s t o r i e s of probands with postaxial Polydactyly without multiple congenital anomalies who have a positive family history of postaxial accessory d i g i t s (polysyndactyly excluded), reveals some inter e s t i n g data regarding penetrance. The number of times Polydactyly can be traced to the paternal l i n e (9) compared to the maternal l i n e (7) i s approximately equal. However among females who transmitted the t r a i t , few expressed i t . In direct, contrast most males who transmitted the t r a i t were themselves polydactylous. This information i s enumerated i n Table XIX for the probands' parents and for individuals i n preceding generations who are.assumed to have transmitted Poly-dactyly. Cases numbers 85 - 87. have not been included i n the table due to the fact that d i g i t a l anomalies noted i n individuals outside the probands' sibships are confined to the preaxial border whereas the proband and sibs have postaxial duplication. In these three families and i n family number 93 no one i n pre-ceding generations can be shown to have transmitted postaxial Polydactyly. Prom the results i t appears postaxial Polydactyly i s nonpenetrant nearly as often as i t i s expressed. This i s most s i g n i f i c a n t considering the hypothesis that expression of a Polydactyly gene i s dependent on the simultaneous presence of an accessory gene. Figures f o r only the probands' parents suggest the 2 : 1 sex r a t i o observed among the probands (postaxial cases) i s due to a high f r e -quency of nonpenetrance among females, and approximately equal numbers of men and women i n h e r i t genes which determine postaxial duplication. These inferences regarding sex r a t i o are somewhat less clear when individuals i n previous gener-ations are included i n the figures. Pedigrees of the postaxial surgical cases of Woolf and Woolf (1970) demonstrate the same phenomena regarding penetrance. In 14 sibships where one parent can be assumed to have transmitted Polydactyly only three out of seven women were themselves polydactylous whereas s i x of the seven men had accessory 79 Table XIX. Penetrance of Postaxial Polydactyly Polydactyly Trait transmitted by Penetrant Nonpenetrant Total Bather . 7 2* 9 male in preceding 6 2+4'* 12 generations mother 2 5 7 female in preceding 3 2 + 2 * 7 generations total 18- 17' 35 *common ancestor of proband and affected relative three or more generations removed (cases numbers 74 andH05) 80 d i g i t s . Adding data from Woolf and Woolf (1970) to the B.C. findings provides a larger sample of postaxial pedigrees, although i t i s now biased i n ascertain-ment of surgical cases. For the pooled cases there i s a t o t a l male : female r a t i o nearer one (28 : 21 ); the'ratio of penetrance to nonpenetrance among men and women remains about one (-27 : 22) whereas th i s r a t i o among males i s approximately 2 : 1 (19 : 9) and among females i s approximately 1 : 2 (8 : 13). There are too few informative cases among the B.C. probands to examine ulnar, f i b u l a r and ul n a r - f i b u l a r pedigrees separately for penetrance among males and females. Ascertainment bias i n the study of Woolf and Woolf makes i t inappropriate to pool cases for such an analysis. As much of the B.C. data on sex and penetrance and that from Woolf and Woolf pertains to u l n a r - f i b u l a r pedigrees, the findings may be more chara c t e r i s t i c of that p a r t i c u l a r type of postaxial duplication. I t should be noted that sex r a t i o shows a v a r i a t i o n between B.C. probands with a family history of ulnar (2.3), f i b u l a r (1.9) and uln a r - f i b u l a r (1.4) types of Polydactyly. In only one cases of r a d i a l Polydactyly (number 18) i s a family history of accessory thumbs c l e a r l y documented. In that case thumb Polydactyly i s expressed by the maternal grandfather and the proband but nonpenetrant i n the child's mother. There i s information suggesting a positive history for three other probands with duplicated thumbs. A maternal r e l a t i v e was presumably affected i n at least two of these families and none of the mothers are known to have a thumb anomaly.. These oases could suggest maternal nonpenetrance of r a d i a l Polydactyly as well. The pedigree of Sinha (1918) also demonstrates maternal nonpenetrance i n a family with u n i l a t e r a l r a d i a l Polydactyly affecting three generations. Occurrence of triphalangeal thumbs was not mentioned. Postaxial Polydactyly unassociated with multiple anomalies can also be examined to f i n d whether the proportion of affected children by sex among families with a positive history of ulnar or f i b u l a r duplication i s equal to 81 the proportion among families with u l n a r - f i b u l a r Polydactyly. Furthermore does the proportion vary depending on the sex of the parent transmitting the t r a i t or whether that parent expresses i t ? Despite the fact that some parents have not completed t h e i r f a m i l i e s , the answer i s suggested by the proportion of polydactylous children i n the probands' sibships plus the proportion i n previous generations f o r which either (a) one parent can be i d e n t i f i e d as having transmitted the t r a i t or (b) two or more sibs were polydactylous or are assumed to have transmitted the t r a i t . This data i s provided i n Table XX. Pedigrees with a. positive history of ulnar or f i b u l a r Polydactyly have been grouped together. .Among them are three' families i n whom the common ancestor was three or four generations back. Findings for ulnar and f i b u l a r Polydactyly are strongly influenced by these cases. The proportion affected among children of polydachylous fathers ( 1 / 2 4 ) and of unaffected fathers who have a positive family" history (2/28) i s not appreciably d i f f e r e n t . Furthermore the l a t t e r figure should be somewhat lower since the number of children i n three sibships was unknown and could not be included. The percentage of affected children among offspring of women transmitting'Polydactyly appears to be very s i m i l a r to figures for men. The findings suggest transmittance of ulnar or f i b u l a r Polydactyly by males and females i s quite independent of i t s expression. There i s a difference i n sex ratio among affected.children of males and of females; fathers appear to transmit Polydactyly more commonly to sons than daughters. In families with a history of ul n a r - f i b u l a r Polydactyly there are no instances of unaffected males transmitting the t r a i t , although i n such families women with normal d i g i t s have had affected sons or daughters. F i f t y percent of the children of polydactylous fathers have been affected. The percentage of polydactylous children (27.7 f°) born to mothers with u l n a r - f i b u l a r d u p l i -cation i s greater than the precentage (6.2 fo) born to unaffected mothers who 82 Table XX. Proportion of Polydactylous Offspring i n Families with Two or More Affected Individuals Number of children A. polydactylous fathers ulnar or f i b u l a r u l n a r - f i b u l a r polydactylous mothers  ulnar or f i b u l a r u l n a r - f i b u l a r B. unaffected fathers, + family history ulnar or f i b u l a r u l n a r - f i b u l a r unaffected mothers, + family history ulnar or f i b u l a r u l n a r - f i b u l a r C. unaffected parents, - family history ulnar or f i b u l a r u l n a r - f i b u l a r polydactylous Percentage normal number of d i g i t s affected —: excluding males females males females sex unk. proband 1 ( 4 ) 5 ( 1 ) - (-) 4 ( 1 ) 1 ( 2 ) - ( - ) - ( 2 ) 1 (D 4 ( 1 ) 4 ( 2 ) - ( 0 9 ( 1 ) - ( 0 1 ( - ) 1 ( - ) - (-) 1 ( - ) - ( 2 ) - (-) 3 ( - ) 9 6 11 4 9 1 11 14 15 7 6 2 24 2 1 4 . 3 5 0 . 0 2 7 . 7 7.1 8 . 3 6 . 2 14 57.1 1 2 . 5 Note: Number of probands totaled separately i n parenthesis. 83 have a family history of th i s type of duplication, however the discrepancy between the proportion of polydactylous children among offspring of affected and unaffected women may well be due to the small number of sibships analyzed. There i s .no excess of affected males among the children with u l n a r - f i b u l a r Polydactyly totaled i n Table XX; the sex r a t i o i s 1 .4 1 among the probands with t h i s type of duplication. I t can be seen among interviewed families with two or more polydactylous individuals (without multiple anomalies), i n few families were a l l affected persons i n the probands' sibships. Considering cases of ulnar duplication and f i b u l a r duplication together, i n only one out of 28 cases without a history of postaxial Polydactyly i n a previous generation was a sib of the proband affected (1/81 s i b s ) . This would suggest that the chances of a second affected c h i l d i n a family with a negative history i s quite low, approximately 1.2$. Of course i t must be remembered that some families i n the study were probably not yet complete. Among ul n a r - f i b u l a r cases, two out of f i v e probands without a hist o r y of Polydactyly p r i o r to the proband's sibship have two or more affected sibs (4/23 s i b s ) . Thus i t appears parents who have a c h i l d with u l n a r - f i b u l a r Polydactyly have a greater chance (17-4 fo) that another w i l l be affected. Also of interest are the figures f o r r a d i a l cases. Nineteen probands without multiple congenital anomalies, which includes the four cases with a positive family h i s t o r y , had 56 sibs, none of whom were polydactylous. F. Conclusions and speculation Although additional pedigrees are necessary i n order to define the genetic component i n the etiology of different jiypes of Polydactyly unassociated with multiple congenital anomalies, the B.C. data points out several i n t e r e s t i n g features. The wide difference i n the B.C. findings between the percentage of positive family h i s t o r i e s among probands affected with u l n a r - f i b u l a r (73 fo) and 84 ulnar (29 %) or f i b u l a r (25 types of Polydactyly could suggest (a) polygenic inheritance of postaxial Polydactyly with r e l a t i v e s of the more severely affected cases, i . e . u l n a r - f i b u l a r cases, constituting a high r i s k group or (b) i n h e r i -tance of ulnar, f i b u l a r and u l n a r - f i b u l a r duplication as separate e n t i t i e s . Considering ulnar and f i b u l a r cases only, data are suggestive of polygenic inheritance due to the fact that the r i s k for sibs of an affected c h i l d with a negative family history of the t r a i t i s less (1.2 fo) than the r i s k for sibs of a proband with an affected r e l a t i v e (approximately 6.6 % ) . Furthermore pedigrees i n which affected individuals are distant cousins are t y p i c a l of polygenic inheritance, however dominant inheritance with reduced penetrance could present the same pattern. Among uln a r - f i b u l a r cases the percentage of affected c h i l d -ren of polydactylous fathers (50 %) and the f a i l u r e to observe nonpenetrance of the Polydactyly gene (genes) among males (both i n the 'B.C. study and the l i t e r a -ture reviewed) strongly suggest dominant inheritance. Yet the sharp reduction i n percentage of affected children of unaffected mothers compared to affected mothers would be expected with polygenic inheritance (Carter, 1969)-The method of Edwards (i960, 1969) to calculate the expected number of affected sibs for a polygenic t r a i t with 100 % h e r i t a b i l i t y gives the following. Combined incidence of ulnar and f i b u l a r Polydactyly i n B.C. equals 0.47 per 1,000 l i v e b i r t h s ; p 2 = 0.0219. Consequently 2.2 % of the 107 sibs of ulnar and f i b u l a r cases would be expected to be polydactylous. Three children have accessory d i g i t s , an observation which f i t s the theoretical value of 2.4 very we l l . For u l n a r - f i b u l a r duplication (p = 0.08 per 1,000; p 2 = 0.009) no poly-dactylous individuals would be expected among 44 sibs (theoretical value, 0.4) whereas 11 sibs with accessory d i g i t s were observed. Lumping a l l postaxial cases (p = 0.55 per 1,000; p 2 = 0.0235) the expected number of affected sibs would be 3.6 children, considerably lower than the observed number of 14. This provides further support that u l n a r - f i b u l a r Polydactyly i s a d i s t i n c t e n t i t y from ulnar and f i b u l a r types of Polydactyly. The r e l a t i v e incidence of ulnar, f i b u l a r and u l n a r - f i b u l a r duplication does not suggest that u l n a r - f i b u l a r Polydactyly results from the coincident occurrence of ulnar and of f i b u l a r Polydactyly, nor does this seem l i k e l y from the segregation patterns observed i n various families. Were i t true that the e n t i t i e s classed as ulnar and as f i b u l a r Polydactyly r e s u l t from the same gene (genes) as ulnar-fibular-duplication, the d i s t i n c t i o n i s s t i l l useful and i t i s the inheritance and/or operation of factors responsible for variable expres-sion which are under analysis. Therefore i t i s the view of the investigator that there exist at least three d i s t i n c t types of preaxial Polydactyly and f i v e types of postaxial Polydactyly: t i b i a l Polydactyly, r a d i a l Polydactyly associated with t r i p h a l -angism, r a d i a l Polydactyly of a biphalangeal thumb, f i b u l a r Polydactyly, ulnar Polydactyly, u l n a r - f i b u l a r Polydactyly, polysyndactyly and synpolydactyly. ( i f ulnar and f i b u l a r synpolydactyly are separate genetic e n t i t i e s , the d i s t i n c -t i o n between f i b u l a r Polydactyly and f i b u l a r synpolydactyly would have to be examined.) D i f f e r e n t i a t i o n between ulnar or f i b u l a r Polydactyly and ulnar-f i b u l a r Polydactyly could be suggested by (a) the presence of nonpenetrance among males, (b) a r e l a t i v e l y high proportion of affected sibs, (c) a tendency for accessory ulnar d i g i t s to be well-developed or accessory f i b u l a r d i g i t s to be syndactylous, or (d) a sex r a t i o considerably d i f f e r e n t from one. B.C. findings suggest r a d i a l Polydactyly of a biphalangeal thumb, ulnar,. and f i b u l a r Polydactyly are each determined by a polygenic mode of inheritance. As yet there i s i n s u f f i c i e n t data for u l n a r - f i b u l a r Polydactyly'to j u s t i f y i postulating anything other than autosomal dominant inheritance with reduced penetrance among females. I f the Polydactyly resulted from the action of a single gene, unequal proportions of affected offspring for polydactylous and 86 " c a r r i e r " mothers could be due to a threshold of a polygenic nature or to seg-regation of factors which i n h i b i t expression. A model consisting of two auto-somal dominant genes would provide an explanation for nonpenetrance, but not for nonpenetrance p r i n c i p a l l y or en t i r e l y confined to the female sex. Further-more on the basis of a two-gene system, assuming no genotype has a selective advantage, half of the children of an affected male would not be expected to have Polydactyly unless the frequency of the accessory gene approached unity. A two-gene model with an X-linked accessory gene recessive i n females and hemi-zygous i n males would give a 1.25 sex r a t i o when p equalled 0.8. Forty percent of the offspring of an affected male would be expected to have Polydactyly; the Polydactyly gene should be nonpenetrant among 20 % of the males who carry i t . F orty-five percent of the offspring of polydactylous females would be affected (50 fo males, 40 % females) whereas polydactylous children'would.comprise 22.5 % of the offspring of " c a r r i e r " women (25 % males, 20 % females). Carrier women would be half as frequent as women who expressed the t r a i t . When more family data from incidence studies are available i t may be clearer which of these theories, i f any, best f i t s the findings f o r u l n a r - f i b u l a r and other types of Polydactyly which have an ir r e g u l a r dominant pattern of inheritance. 87 V I I I . Multiple Congenital Anomalies Polydactyly has been noted i n association with a number of congenital malformations. In some instances this association i s probably fortuitous whereas i n others the anomalies appear to have a common etiology. The incidence and nature of additional congenital anomalies among the probands of the B.C. study i s presented i n t h i s section and compared to the "general population". Types of duplication seen i n the probands with additional anomalies are summar-ized. In addition a table l i s t i n g syndromes and anomaly complexes i n which Polydactyly has been noted has been compiled from the l i t e r a t u r e , and a b r i e f review of syndromes of interest, including comments from B.C. data on syndromes diagnosed i n one or more probands, follows. A. Introduction I t i s of interest to know whether infants with supernumerary d i g i t s have additional anomalies more frequently than newborns of the general population. Anomalies recorded i n the medical records of the probands are given i n Appendix A. A major anomaly has been defined as "one which has an adverse effect on either the function or s o c i a l a c c e p t i b i l i t y of the i n d i v i d u a l " (Marden et a l . , 1964, p. 357), whereas a minor one i s not a medical or cosmetic problem. An ind i v i d u a l with one major anomaly is'more l i k e l y to present some other major and/or minor defect than i s an ind i v i d u a l chosen at random. Minor anomalies occur independently and do not tend to cluster unless associated with a major defect (Marden et a l . , 1964; Hook and Petry, 1970). In the studies of Marden et a l . (1964) and Hook and Petry (1970) super-numerary d i g i t s were considered to be either a minor or a major anomaly depending upon the examiner's evaluation of the severity of the duplication. This sub-je c t i v e method disregards the v a r i a b i l i t y of expression found with Polydactyly: v a r i a b i l i t y among affected persons of the same family and seen i n syndromes associated'with supernumerary d i g i t s . Furthermore an ind i v i d u a l with more than one extra d i g i t may present a rudimentary and also a well-formed extra finger(s) and/or toes(s). As there seems to be no natural dichotomy into "major" and "minor" forms of Polydactyly, and supernumerary d i g i t s are a feature of the population studied, t h i s anomaly w i l l not be referred to as a major or minor malformation i n the results which follow. B. . Results Minor anomalies. To our knowledge 105 out of 138 children do not have a major malformation. The presence of a single minor anomaly has been noted i n 12 children (12/105), nine boys and three g i r l s , and two minor anomalies i n one additional boy. As no special measures were taken to assess minor anomalies i n the cohort the figure of ..113 out of 138 probands (9 fo) with a minor anomaly i s undoubtedly low. The minor anomalies recorded are: hemangiomas located other than on face or neck ( 5 ) , p i l o n i d a l dimple or sinus ( 2 ) , abnormal ears ( 2 ) , supernumerary nipples ( l ) , preauricular skin tags ( 2 ) , abnormal buttock crease (1 ) and a n t i -mongoloid slant of palpebral fissures ( l ) . Hernia and hemangiomas of the face or neck were noted i n f i v e and three children respectively; these anomalies were categorized as normal phenotypic variants by Marden et a l . (1964). In addition four children had a tongue-tie clipped. Dermatoglyphics were not investigated i n many of the B.C. children and have not been included. I t should be noted that abnormal palmar creases accounted for approximately 30 % of the isolated minor anomalies observed by Marden and colleagues. The 13 children whose minor anomalies are-consistent with those t a l l i e d i n the Madison, and Albany studies presented various forms of Polydactyly. Description of the supernumerary d i g i t s i s given in' Table XXI. Among children with no major defect, minor anomalies are most frequently seen i n conjunction. 89 Table XXI. Type of Polydactyly Presented by Children with a Minor Anomaly Description Border No. of cases skin tag duplicated d i s t a l phalanx rudimentary d i g i t one or more well-formed d i g i t s unknown L r a d i a l L r a d i a l R r a d i a l R ulnar B ulnar R ulnar, R f i b u l a r L ulnar, B f i b u l a r B ulnar B f i b u l a r B ulnar, B f i b u l a r B "feet" 90 with postaxial duplication involving the hands and feet (3/16) and with d u p l i -cation of the thumb (4/31 ). Few children with solely ulnar (4/54) or f i b u l a r (1/24) d u p l i c a t i on are known to have a minor anomaly. Although the Polydactyly i n cases with a minor anomaly tends to be rudimentary, rudimentary forms com-prise the bulk of the cases i n the study and t h i s would appear of limited significance. None of the s p e c i f i c minor anomalies presented by the probands are known to show a p a r t i c u l a r association with supernumerary d i g i t s , and with the exception of p i l o n i d a l sinus are among those anomalies most commonly found i n the study of Marden et a l . (1964). Single ma.jor anomalies. A single major anomaly has been noted i n nine of the polydactylous children (6 g i r l s , 3 boys); t h i s i s approximately 6.5 $ of the cohort. The major anomalies seen were: syndactyly, other than that com-monly seen of toes 2-3 or polysyndactylous duplication of a d i g i t ( 2 ) , cataract ( 2 ) , strabismus ( 2 ) , c l e f t palate ( l ) , enlarged l i v e r (1) and hypoglycemia ( l ) . The association of poly- and syndactyly inttwo cases i s probably not random. Although cases with c l e f t palate and postaxial or preaxial supernumerary d i g i t s have been described (see Table XXV) and the association of postaxial Polydactyly and median c l e f t of the upper l i p has been designated a syndrome (Temtamy & McKusick, 1969), the occurrence of c l e f t palate and thumb Polydactyly as seen i n one proband i s not known to be associated. The significance of eye defect with extra d i g i t s i s not clear. In these four cases and the remaining two the occurrence of Polydactyly and a major anomaly may well be due to indepen-dent events. ..Minor anomalies noted i n two children are: deformed f i f t h finger and f i s t u l a of a tear-sac (1) and p i l o n i d a l sinus ( l ) . The nine probands presented diverse forms of Polydactyly. Description of the supernumerary d i g i t s i s given i n Table XXII. The frequency of a single major anomaly among children with different types of Polydactyly i s : 91 Table XXII. Type of Polydactyly Presented by Children with One Major Anomaly Description Border No. of cases duplicated d i s t a l phalanx b i f i d proximal phalanx pedicle well-formed d i g i t unknown L r a d i a l B t i b i a l B r a d i a l L ulnar R ulnar B ulnar L f i b u l a r B ulnar, B f i b u l a r 92 t i b i a l ( 1/6) , r a d i a l (2/31), ulnar ( 4 / 5 4 ) , f i b u l a r (1/24) and u l n a r - f i b u l a r ( l / l 6 ) . Extent of duplication appears to be i r r e l e v a n t ; a major malformation i s no more l i k e l y to coincide with the occurrence of well-formed extra d i g i t s than rudimentary ones. This tends to mask the fact that i n some cases undoubtedly the type of duplication i s dictated by the same dysfunction as the major anomaly. Multiple major anomalies. There are 24 children i n the Polydactyly study with two or more major malformations, 18 boys and 6 g i r l s . This i s 17 % of the cohort. In some cases the multiple major anomalies presented by the poly-dactylous children have been recognized as a s p e c i f i c syndrome or c l i n i c a l e n t i t y . Of these, i n a l l but perhaps the l a s t two, Polydactyly i s known to show more than a random association: trisomy D^  syndrome ( j ) , Smith-Lemli-Opitz .syndrome ( 3 ) , polydactyly/imperforate anus/vertebral anomalies syndrome ( l ) , polycystic kidneys, i n t e r n a l hydrocephalus and postaxial Polydactyly ( l ) , Down's syndrome ( l ) , Laurence-Moon-Biedl syndrome ( l ) , Pierre Robin anomaly ( l ) and giant c e l l h e p a t i t i s ( l ) . In addition there are 12 cases attributed to unknown etiology. Seven of these have anomalies suggestive of one of the f i r s t three syndromes above including one case which was noted to closely resemble trisomy 17-18 syndrome and another casev/which was described as a form of cyclopia. P r i n c i p a l among anomalies i n the remaining f i v e cases are heart defect along with other anomalies (4) and multiple cephalic defects ( l ) . As would be expected, minor anomalies were commonly noted i n children with multiple con-genit a l anomalies (18/22 or 82 % ) . Minor anomalies are given i n the case descriptions i n Appendix A. Supernumerary d i g i t s i n children with multiple major anomalies tend to be more complete forms of duplication. Description of the d i g i t s i s given i n Table XXIII. A large number of children with multiple major anomalies have 93 Table XXIII. Type of Polydactyly Presented by Children with Multiple Major Anomalies Description Border No. of cases duplicated d i s t a l phalanx pedicle one or more well-formed d i g i t s unknown5 R r a d i a l L r a d i a l R r a d i a l L ulnar B ulnar R f i b u l a r R r a d i a l B f i b u l a r B ulnar, L f i b u l a r B ulnar, R f i b u l a r B ulnar, B f i b u l a r R ulnar L ulnar B ulnar R "hand" "Polydactyly" . 94 ulnar and f i b u l a r (7/16) Polydactyly. In each case there i s at least one w e l l -formed extra d i g i t which may a r t i c u l a t e . Twelve of the 16 cases with ulnar and f i b u l a r accessory d i g i t s have at least one extra d i g i t described as well-formed. Thus 60 f> ( 7 / 1 2 ) of the probands with polydactylous hands and feet both have multiple major anomalies. This i s 29 f° of the children with multiple major anomalies. Children presenting ulnar and f i b u l a r duplication include one case of giant c e l l h e patitis and one case each of Laurence-Moon-Biedl syndrome, Poly-dactyly/imperforate anus/vertebral anomalies syndrome and Smith-Lemli-Opitz syndrome. L i t t l e can be said about the extent of duplication i n cases with ulnar supernumerary d i g i t s since among cases with descriptions the accessory d i g i t s were a l l termed pedicles ( 5 / 9 ) . The syndromes seen i n probands with ulnar duplication are Smith-Lemli-Opitz syndrome ( 2 ) , polycystic kidneys, int e r n a l hydrocephalus and postaxial Polydactyly ( l ) , and trisomy D.j syndrome. The c h i l d noted to resemble trisomy 17-18 syndrome also presented ulnar d i g i t s . Syndromes diagnosed i n probands with r a d i a l ( 4 ) and f i b u l a r ( 2 ) Polydactyly are Down's syndrome and Pierre Robin anomaly respectively. Duplication i n these two cases i s quite complete; i n additional cases with r a d i a l ( 2 / 4 ) and f i b u l a r ( 1 / 2 ) Poly-dactyly the extra d i g i t s were described as pedicles. In addition the c h i l d noted to present cyclopia had r a d i a l Polydactyly. Further comment on this and other cases may be found i n the review of syndromes. C. Discussion To what extent i s the frequency of major and minor anomalies i n poly-dactylous children greater than that of the general population? In a survey by Marden et a l . (1964) 4 , 4 1 2 newborn babies i n Madison were checked for minor and major anomalies detectable by surface examination. Among 4 , 3 2 2 babies with no major malformation there were 574 with one • minor anomaly and 35 with 95 two or more minor anomalies. The presence of one or more minor anomalies was not unusual and was found i n 14 f> of the infants. The percentage of infants with one minor anomaly who had an additional minor anomaly(s) was 5.7 f° (35/609). The frequency of one (22.4 f°) or more (6.9 f°) minor anomalies was increased among infants with a single major malformation. A s i m i l a r study by Hook and Petry (1970) of 200 newborns i n Albany found 58 babies to have one minor anomaly and 21 to have two or more minor anomalies. The frequency of a.minor anomaly (39.5 f°) and the coincident occurrence of minor anomalies (26 fo) was considerably higher i n the Albany newborn population. Undoubtedly some of th i s difference r e f l e c t s the examiners' interpretation of minor and major anomaly. However the s i g n i f i c a n t fact i s that i n both studies the occurrence of minor anomalies i n the absence of a major defect f i t s a ran-dom d i s t r i b u t i o n . The difference i n means of ascertaining minor anomalies l i m i t s comparison between the Madison and Albany studies which were both set up s p e c i f i c a l l y to determine minor anomalies and the B.C. study i n which this information was gleaned from medical records. There i s the suggestion however that supernumer-ary d i g i t s i n r e l a t i o n to the occurrence of a minor anomaly assume the importance of a minor anomaly for several reasons: (a) among polydactylous children the low frequency of additional minor anomalies i n the absence of a major defect (9 f) compared to the frequency when one (approximately 22 fo) or more (approxi-mately 82 fo) major anomalies are present does not suggest there i s a clustering e f f e c t ; ( i t i s true however that medical records tend to be more complete f o r infants with serious malformations.); (b) the B.C.. figure (9 fo), taking into account i t s minimal nature, i s not incompatible with the frequency (26 fo) found for the random association of two minor anomalies (Hook & Petry, 1970); and (c) regarding children with no major defect, the frequency of additional minor anomalies noted i n polydactylous children does not exceed the frequency 96 observed i n newborns of the general population (14$) studied by Marden and colleagues (1964). Thirty-lhree out of 138 children with supernumerary d i g i t s (24 $) have one or more major anomalies. This includes anomalies detected after the new-born period for those children on whom additional information was available. These findings can be compared with the survey of 5,739 newborns by Mcintosh et a l . (1954)." Some of the children were followed f o r f i v e years; at the con-clusion of the study the incidence of major anomalies was 7.5 $. This would indicate that a major defect occurs approximately 34" times more frequently among children with Polydactyly. In order to compare the Polydactyly study results with those of Marden et a l . , two cases have been subtracted due to the fact that newborns i n the Madison study were not examined for certain anomalies of the central nervous system, or the cardiovascular, g a s t r o i n t e s t i n a l and renal systems. After t h i s correction i t appears a single major anomaly.(5.0 fo) occurs four.times more frequently i n the polydactylous children than i n the Madison newborn popula-t i o n (58/4,412 or 1.3 f°) and occurs about twice as often i n the Polydactyly group than i n Madison babies who have a minor anomaly (17/609 or 2.8 fo). The frequency of supernumerary d i g i t s and a single major anomaly occurring together i s less by half however than the l i k e l i h o o d that a case of the Madison popula-t i o n with one major malformation would present one other major defect as w e l l . The percentage of children i n the Polydactyly group with two or more major malformations (24/138, 17 f>) i s approximately 25 times the frequency of multiple major anomalies i n infants of the Madison population (32/4,412, 0.7$). And at least 73 f> (24/33) of the polydactylous children with a major malforma-t i o n have multiple defects i n contrast to a figure of 35 f° f o r the Madison population. Thus the l i k e l i h o o d that a c h i l d with Polydactyly w i l l have addi-t i o n a l minor anomalies or a single major anomaly i s not much greater than that 97 of a c h i l d born with a given minor malformation; but having noted one major malformation i n a c h i l d with Polydactyly and i n a c h i l d without, the one with Polydactyly i s twice as l i k e l y to have additional major anomalies. The B.C. study has a greater frequency of children with additional anomalies than was found by Tan (1969) among 42 polydactylous infants. In the Singapore study there were 7 cases with one or more additional anomalies: E l l i s - v a n Creveld syndrome ( l ) , Down's syndrome ( 2 ) , trisomy D^  syndrome (1) imperforate anus (1), syndactyly of toes 4-5 ( l ) , and preauricular skin tag ( l ) . Postulating that the infant with imperforate anus was an unrecognized case of Polydactyly/ imperforate anus/vertebral anomalies syndrome, 12 fo (5/42) of the polydactylous children had multiple anomalies. In the study by Neel (1958), among 60 polydactylous children, 13 (21.6 fo) had two or more congenital anomalies. Prom data given i t would appear that s i x cases (10 fo) had a single additional major anomaly and seven cases (1T.6 fo) had multiple congenital anomalies. These, figures show approximately a seven f o l d increase i n the number of children with major defect over the general population of Japanese infants studied. The extraordinary incidence of multiple congenital anomalies among c h i l d -ren with supernumerary d i g i t s i s due to the fact that Polydactyly occurs i n association with a number of other malformations at a frequency greater than the product of t h e i r respective frequencies. Comparison of the types of duplication seen i n B.C. probands with additional anomalies, given i n Table XXIV, reveals one group of cases i n which there i s a greater association with additional anomalies. Two-thirds of the cases of postaxial duplication of the hands and feet have additional malformations, followed i n order of decreasing frequency by r a d i a l , ulnar, f i b u l a r and t i b i a l Polydactyly. Postaxial forms tend to be b i l a t e r a l and a greater percentage of well-developed forms are associated with multiple anomalies. Thus i n some cases Polydactyly i s a good 98 Table XXIV. Type of Polydactyly Associated with Additional Congenital Anomalies Type of No. of cases Minor anomaly One major Multiple major duplication i n study only anomaly anomalies  t i b i a l C6 - 1 - 1 r a d i a l 31 4 2 4 10 ulnar 54 4 4 9 17 f i b u l a r 24 1 1 2 4 ulnar & f i b u l a r ;i;_6 3 1 7 •11 unknown 7 1 - 2* 3 t o t a l 138 13 • 9 '-"' 24 46 *one of hand i n d i c a t o r of extensive developmental disturbances leading to multiple congeni-t a l anomalies. D. Syndromes The d i s t r i b u t i o n of cases with multiple major anomalies regarding type of Polydactyly expressed would seem i n large measure dependent on the incidence of various syndromes and the frequency of Polydactyly i n each. Table XXV l i s t s syndromes and anomaly complexes i n which Polydactyly occurs. Ulnar and u l n a r - f i b u l a r duplication are cha r a c t e r i s t i c of several syndromes, some of which have a r e l a t i v e l y high incidence; and i t may be seen i n a number of others. Fibular Polydactyly, d i s t i n c t from the variable expression of ulnar-f i b u l a r Polydactyly, c h a r a c t e r i s t i c a l l y does not associate with anomalies other than syndactyly. Considering preaxial Polydactyly, t i b i a l duplication i s generally l i m i t e d to syndromes with polysyndactyly whereas r a d i a l duplication tends to be the extreme of a range of thumb abnormalities i n some syndromes, to occur as a component of polysyndactyly, or to occur at a low frequency i n a l i m i t e d number of additional syndromes. Down's syndrome. Mongolism was described by Down i n 1866 and has a number of distinguishing features i n the newborn which are presented i n Table XXVI. Trisomy of chromosome 21 was noted i n patients with the syndrome by Lejeune et a l . (1959); few reported individuals with the cluster of stigmata seen i n the syndrome have had no recognizeable excess of chromosome (21) material ( H a l l , 1964). Although the developmental anomalies effected by com-plete or p a r t i a l trisomy of the number 21 chromosome do not usually include Polydactyly, i t does occur. In a.study i n Massachusetts, Fabia and Drolette (1970) ascertained 2,774 liveborn infants with Down's syndrome born between 1 January 1950 and 1 January 1967, an incidence of 1.32 per 1,000 l i v e b i r t h s . Table XXV. Syndromes and Anomaly Complexes Associated with Duplicated D i g i t s Radial T i b i a l Ulnar Fibular Uln^fib. Postax. Congenital anemia & triphalangeal thumbs (Aase & Smith, 196©) B/G translocation associated with multiple congenital anomalies (Fitzgerald & Neal, 1964) F a m i l i a l absence of middle phalanges with n a i l dysplasia (Bass, 1968) Translocation 3/B syndrome (Walzer et a l , 1966) Polvsynd Sy nP° 1y d & Unusual duplic. polyd. polyd. polyd. polyd. polyd. J * t i b i a l dup. polyd. t r i p h ? biph X biphal biphal Triphalangeal thumbs with t i b i a l defect t r i p h & preaxial Polydactyly (Salzer, 1960) Triphalangeal thumbs & great toes associated with other anomalies (Qazi-& Smithwick, 1970) Holt-Oram syndrome Thalidomide embryopathy Pelizaeus-Merzbacher's disease with s k e l e t a l malformations (Gibson, 1961) U l l r i c h - F e i c h t i g e r syndrome t r i p h ? biph t r i p h ? biph t r i p h Polydactyly/imperforate-anus/vertebral t r i p h anomalies syndrome biphal X t r i p h t r i p h X X 7th X X X 7th o o Table XXV. (continued) Cyclopia Down's syndrome Trisomy 1 7 - 1 8 syndrome Microphthalmia, anpphthalmos with d i g i t a l anomalies. D trisomy syndrome Polydactyly with median c l e f t upper l i p Smith-Lemli-Opitz syndrome E l l i s van Creveld syndrome Polydactyly with c l e f t l i p and/or palate. Laurence-Moon—Biedl syndrome Biemond's syndrome I I O r o - f a c i a l — d i g i t a l syndrome I Mohr syndrome (OPD II) Rubinstein-Taybi syndrome Prontodigital syndrome Polysyndactyly with peculiar s k u l l shape Radial T i b i a l Ulnar Eibular Uln-fib. Postax. _ n - n Synpolyd & Unusual Polysynd. J v J duplic. polyd. polyd. polyd, polyd. polyd. t i b i a l dup. polyd. X X X X X broad X X X X X X X X X X. X X X X X X X X X X X X X X X X (fib.) X (fib.) X (fib.) X (fib.) X X X 7th 7th 7th X Table XXV. (continued) Radial T i b i a l Ulnar Fibular U l n - f i b . Postax. p Synpolyd & Unusual polyd. polyd. polyd. polyd. polyd. polyd. • t i b i a l dup. polyd. Goltz;'s syndrome X Noack's syndrome (ACPS i ) / X Carpenter's syndrome (ACPS II) X Waardenburg's type ACS: X P f e i f f e r ' s type ACS- X Robinson type ectodermal dysplasia X (Robinson et a l , 1962) Hexadactyly, mandibular fissur e & X oligodontia (Weyers, 1953) Pierre Robin anomaly with Polydactyly X Diabetic embryopathy (Lenz, 1966) ? X Thoracic asphyxiant dystrophy X- X Oliver's syndrome (Oliver, 1940) X Polycystic kidneys, internal hydrocephalus X & Polydactyly (Simoupolis et a l , 1967) Polydactyly of the second metatarsal X with associated defects of the feet (Neel & Rusk, 1963) F-form of aero—pectoro-vertebral X dysplasia (Grosse et a l , 1969) 103 Table XXVI. Cardinal Features of the Newborn with Down's Syndrome h y p e r f l e x i b i l i t y muscle hypotonia lack of Moro r e f l e x f l a t f a c i a l p r o f i l e oblique palpebral fissures dysplastic ears neck folds simian crease dysplastic middle phalanges d i g i t V dysplastic pelves Source: H a l l (1964) 104 Among them were two females with Polydactyly and f i v e males with b i f i d thumb, a<> prevalence per 1,000 liveborn mongols of 0.8 and 2.1 respectively. Tan (1969) found two polydactylous infants with Down's syndrome i n his study. Both infants had u n i l a t e r a l thumb Polydactyly, one with a b i f i d proximal phalanx right and the other with a supernumerary thumb a r t i c u l a t i n g with the l e f t f i r s t . metacarpal. Another case with an extra thumb was found among 38 mongols i n a study of newborns i n Sweden (H a l l , 1964). One male infant (proband number 6) with Down's syndrome and polydactylous l e f t thumb was ascertained i n the B. C. Polydactyly study. In these four studies there were nine cases (6 /6 males) with ?.unilateral thumb Polydactyly and two cases with ? postaxial Polydactyly. Whether there could be a family history for supernumerary d i g i t s i n the l a t t e r two cases was not indicated. Radial duplication appears to be the most common type of Poly-dactyly i n trisomy 21 syndrome; the association i s probably not coincidental since the frequency of th i s type of duplication i s higher i n the mongol popula-ti o n , 2.1 per 1,000 (Pabia & Drolette, 1970), than i n the predominantly Caucasian population of B. C. (0.20 per 1,000) or the.Chinese, Malay and Indian population of the Singapore study (0.63 per 1,000). Trisomy 17-18 syndrome. Trisomy of a 17—18 chromosome was f i r s t reported by Edwards et a l . (i960) and subsequently more than 180 cases have been recorded. There i s a s t r i k i n g preponderance of females, 113 out of 143 patients or 77 % (Taylor, 1968). Using figures from f i v e studies (Hecht et a l . , 1963; Smith, 1964; Taylor & Moores, 1967; Taylor,• 1968; Benady & Harris, 1969), incidence can be estimated at 0.17. per 1,000 newborns or 1 per 6,040. Findings i n patients with a trisomic E complement are presented i n Table XXVII. Polydactyly i s not characteristic of the syndrome but i t does occur. Among 87 cases from the l i t e r a t u r e (references for the cases i d e n t i f i e d i n Appendix C) 105 Table XXVII. C l i n i c a l Features of Trisomy 17-18 Syndrome hypertonia elongated or odd s k u l l ocular hypertelorism lowset and/or malformed ears micrognathia short neck short sternum congenital heart defect renal anomaly cryptorchidism limited hip abduction abnormal thumbs fl e x i o n deformities of fingers overlapping fingers short and/or dorsiflexed big toe prominent calcaneus Source: Smith et a l , 1960; Lewis, 1964; Taylor, 1968 106 and an additional 13 from the f i l e s of U.B.C, Division of Medical Genetics, f i v e cases were reported to have supernumerary fingers. This review of cases was prompted by the note that proband number 133 resembled patients with trisomy 17-18 syndrome. Chromosome studies were not done on the proband and this case has not been included i n the tabulation of cases. In four cases of trisomy 17-18 the extra d i g i t s were noted to be b i l a t e r a l and i n one case u n i l a t e r a l . One patient was described as having rudimentary s i x t h fingers, i n the others the extra d i g i t s may have been well formed. Although the border of the hand was specified i n only one case (ulnar) i t i s resonable to suspect that the other cases or most of the others were also ulnar. Besides Polydactyly of the hand (5/100), reduction deformities of the thumb and/or radius (12/100), hypoplastic l e f t f i f t h finger (l/lOO), broad or large f i r s t toes ( 4 / 1 O O ) hypoplastic f i r s t toes (l/lOO) and absence of the l e f t foot (1/100) ..have been described. Therefore i t appears that an extra 17-18 chromo-some, i n addition to the more common anomalies of the extremities, also effects a range of d i g i t a l reduction and duplication somewhat similar'to that seen i n the polydactyly/imperforate anus/vertebral anomalies syndrome with abnormal development of the postaxial or the preaxial borders, more commonly of the hands than of the feet. Trisomy D^  syndrome. Patau et a l . (i960) associated a s p e c i f i c pattern of anomalies with an extra group 13-15 chromosome. Details on 221 c y t o l o g i c a l l y confirmed cases were reviewed by Magenis et a l . (1968) who found 178 cases (80.5 i°) with seven separate D chromosomes, 30 (13.6 fo) with either translo-cation or isochromosome and 13 ('5.9 %) with trisomy/normal mosaicism. Based on physical findings the syndrome has been reported i n additional patients who have not had chromosome investigations or whose karyotype appeared to be either ambiguous or not D. trisomy. Pooling data from four studies establishes 107 an incidence of 0.13 per 1,000 newborns or 1 per 7,770 (Smith, 1964; Taylor & Moores, 1967; Taylor, 1968; Yu et a l . , 1970). The sex r a t i o i s approximately equal with only a s l i g h t excess of females: male to female r a t i o of 0.92 (Magenis et a l . , 1968). Physical findings most frequently seen i n the syndrome are l i s t e d i n Table XXVIII. •Details on the d i g i t a l anomalies have been compiled for 101 cases which are tabulated i n Appendix C and come mainly from the l i t e r a t u r e . Included i n the table are probands numbers 43, 46 and 70. No attempt has been made to d i f f e r e n -t i a t e between cases with seven D chromosomes, translocation or mosaicism. The anomalies reported i n these cases include r e t r o f l e x i b l e thumbs, f l e x i o n deformities of the fingers, hyperconvex f i n g e r n a i l s , broad and/or long f i r s t toes, angulated or dorsiflexed f i r s t toes, hypoplastic toenails, syndactyly and Polydactyly. Pew cases were reported to have normal extremities. The preaxial anomaly of the hands which was consistently noted i s r e t r o -f l e x i b l e thumbs. In the series of patients of Table XXVIII this was noted i n 17 out of 42 children (40 fo). Abnormal development of the preaxial border of the feet was less frequently reported (16/101 patients, 16 fo) and included Polydactyly ( 3 ) and extremely broad and/or long f i r s t toes (8), and dorsiflexion (6). Ten of the 16 cases with abnormal f i r s t toes also had postaxial Polydactyly. Polydactyly was present i n 71 out of 101 cases (see Table XXIX). Because duplication i s predominantly postaxial i n the D| trisomy syndrome, i f a case description f a i l e d to specify the border affected, i t was assumed to be ulnar and/or fibular.. The hands alone (29) or the hands and feet ( 2 4 ) are most often affected. In general, extra d i g i t s of the hand are more l i k e l y to be rudimentary than those of the foot. Duplication tends to be b i l a t e r a l (31) rather than u n i l a t e r a l (18) or a combination of the two (11). When u n i l a t e r a l , the extra d i g i t i s frequently located on the l e f t hand (15/18) or foot (9/13). Pour cases had 108 Table XXVIII. C l i n i c a l Features of Trisomy Syndrome No. of cases microcephaly, often with sloping forehead 25/36 holoprosencephaly type defect with varying 23/31 degrees of incomplete development of forebrain and olfactory and optic nerves defects i n cr a n i o f a c i a l development from hypo- 35/41 telorism to cebocephaly and cyclopia microphthalmos 29/43 ocular defects, often i r i s colobomata 32/44 c l e f t l i p and/or c l e f t palate 31/44 micrognathia 27/32 lowset malformed ears 28/36 apparent deafness or hearing loss 19/29 c a p i l l a r y hemangiomata, often of forehead 24/39 soft tissue defects with redundant folds i n 11/15 the mandibular and p e r i o r b i t a l regions Polydactyly, occasionally syndactyly 31/43 r e t r o f l e x i b l e thumbs 17/42 f l e x i o n deformity of fingers 21/32 hyperconvex finge r n a i l s 28/38 posterior prominence of heel 20/43 cardiac abnormality: including VSD, PM, ASD, 31/42 dextro-position... malformed ri b s with asymmetry of bony thorax 6/ 8 renal anomalies 11/18 umbilical or inguinal hernia, abdominal wall 20/43 abnormalities cryptorchidism, abnormal scrotum i n males 17/20 bicornuate or biseptate uterus, ovarian 11/12 abnormalities i n females Source: Snodgrass et a l . , 1966; Taylor, 1968; James et a l . , 1969; Taylor et a l . , 1970. 109 Table XXIX. Site of Polydactyly i n Trisomy D, Syndrome No. of cases L ulnar 9 R ulnar 3 B ulnar 17 • t o t a l 29 B ulnar, B f i b u l a r 11 B ulnar, L f i b u l a r 2 B ulnar, R f i b u l a r 4 B ulnar, U f i b u l a r 1 L ulnar, B f i b u l a r 2 L ulnar, L f i b u l a r 4 t o t a l 24 L f i b u l a r 2 B f i b u l a r 2 B f i b u l a r , L t i b i a l 1 L f i b u l a r , B t i b i a l 1 B t i b i a l . 1 t o t a l 7 extremity unknown 11 t o t a l 11 t o t a l 71 Source: see Appendix C 110. seven d i g i t s on the l e f t extremity, i n two cases there was t i b i a l and f i b u l a r Polydactyly, i n a t h i r d there was an extra finger inserted between the t h i r d and fourth d i g i t s and a postminimus, and for the fourth there was no further des-c r i p t i o n of the hand. Finding ten cases with broad and/or long or duplicated f i r s t toes, f i v e which exhibit postaxial Polydactyly as w e l l , makes i t necessary -to consider that trisomy of a D or.part.of a D chromosome effects or contributes to d u p l i -cation of both borders of the extremities. V a r i a b i l i t y i n expression of d i g i t a l duplication implies dysfunction may occur over a broad time span, but presumably too l a t e to s i g n i f i c a n t l y affect the formation of thumb anlagen':., as no cases are known to have duplicated or broad thumbs. Cyclopia. Cyclopia i s characterized by anomalous development of the eyes, nose, s k u l l and brain ( W i l l i s , 1958). The s t r i k i n g f a c i a l defect ranges i n severity; most frequently there i s a central diamond-shaped palpebral f i s s u r e with"a single globe manifesting various degrees of doubling of the i n t r i n s i c structures" (Gorlin & Pindborg, 1964, p. 179). Often a proboscis-like appendage representing the nose i s located above the eye on the lower part of the forehead (Sedano & Gorlin, 1963). In t h e i r review i t was noted that more than 250 cases have been reported, of which 60 fo were females. Mitani (1954) gave a prevalence figure of 0.06 per 1,000 for cyclopia and cebocephaly among infants whereas these anomalies were as frequent as 6.2 per 1,000 among embryos of 5.5 - 30 mm CRL (Mshimura, 1970). Sarma (1963) found cyclopia was often associated with high p a r i t y and hydramnios. Cyclopia i s not exclusively an isolated defect. An association with Polydactyly i s well documented i n the l i t e r a t u r e and has occurred i n approxi-mately 6 fo of the cases described. Although supernumerary d i g i t s are the most common sk e l e t a l anomaly seen with cyclopia (Potter, 1952), other congeni-111 t a l anomalies have been observed, p a r t i c u l a r l y anomalies common with trisomy syndrome. The observation' of a trisomic D complement i n cyclopic (Toews & Jones, 1968) and cebocephalic infants (McKusick, 1961; Buhler et a l . , 1962) confirmed the suspicion that these malformations are extremes i n the range of abnormal prosencephalon cleavage of trisomy syndrome. Undoubtedly some of the previous reports o f infants with cyclopia and postaxial Polydactyly were cases of trisomy. However, perhaps not a l l cases with postaxial duplication result from the presence of an extra D chromosome. Supernumerary d i g i t s of the ulnar border or the ulnar and f i b u l a r borders have been described (see Table XXX); most often seen are f a i r l y hypoplastic accessory f i f t h fingers on both \ hands. The Polydactyly seen with cyclopia is. not lim i t e d to the postaxial border and several infants with thumb Polydactyly have been described. Radial d u p l i -cation occurs less frequently than postaxial (Sedano & Gorlin, 1963). An idea of the r e l a t i v e frequency i s given by Potter (1952) who found among 15 infants with some degree of cyclopia or cebocephaly, s i x with b i l a t e r a l accessory ulnar d i g i t s and one with duplication of the thumbs. One newborn described as having a cyclopia type defect and u n i l a t e r a l Polydactyly of the righ t thumb was ascer-tained i n the B.C. Polydactyly study (case number 14), an incidence of 0.07 per 10,000 or 1 per 136,730 l i v e - and s t i l l b o r n infants. The etiology of cases with thumb Polydactyly most l i k e l y d i f f e r s from at least a proportion of the cases with postaxial Polydactyly since r a d i a l d u p l i -cation i s not known to occur with trisomy. Other chromosomal errors have been found in f f o u r cases of cyclopia: two with deletion or p a r t i a l deletion of the short arm of chromosome 18 (? 17) (Paint & Lewis, 1964; Nitowsky et a l . , 1966), one with mosaicism f o r monosomy of a G chromosome (Cohen, 1966) and the fourth infant with an abnormal karyotype who was postulated to have deletion of a "small chromosome segment" and whose family history includes three other 112 Table XXX. Cases of Polydactyly Associated with Cyclopia Reference No. of Type of Polydactyly and cases Sex additional anomalies when given Durlacher (1915) 1 Boyd and M i l l e s (1951) 1 Rysanek (i960) . 1 Potter (1952) 6 Sarma (1963) ' 1 Sarma (1963) . 1 Sedano and Gorlin (1963) 1 Potter (1952) 1 C a r l i and Torre (1961) 1 Sarma (1963) 1 B.C. study, proband no. 14 1 Chapman (1936) 1 Sarma (1963) 1 P f i t z e r and Muntefering (1968) 1 M L ulnar, L f i b u l a r Polydactyly F R postminimus, small scar at corresponding position L hand F B ulnar and f i b u l a r Polydactyly, accessory d i g i t s well-formed; bicornuate uterus - B ulnar Polydactyly M B ulnar, R f i b u l a r Polydactyly F R ulnar Polydactyly F R postminimus, L accessory toe, well-formed B r a d i a l Polydactyly F R r a d i a l Polydactyly, terminal phalanx reduplicated; preauri-cular appendage L F R thumb b i f i d ; anencephaly F R r a d i a l Polydactyly (see case description, Appendix A) M L hand with s i x fingers; hypo-p l a s t i c genitalia' F s i x d i g i t s on each hand - Polydactyly, border unknown (one of four related individuals with cyclopia) Note: In addition the cases of E l l i s (1866) and Ploucquet (cited by E l l i s , 1866) presented Polydactyly with cebocephaly. 113 cases of cyclops deformity ( P f i t z e r & Muntefering, 1968). Although Polydactyly was not present i n any of these cases, i t can he expected that Polydactyly associated with alobar holoprosencephaly may re s u l t from more than one abnormal condition which affects the early development of the embryo. Polydactyly/imperforate anus/vertebral anomalies syndrome. In 1968 Say and Gerald described ten patients with a polydactyly/imperforate anus/verte-b r a l anomalies [P/IA/VA] syndrome. Since that o r i g i n a l report, 19 additional patients have been described with s i m i l a r features and a number of accounts of imperforate anus i n association with d i g i t a l and additional anomalies can be •found i n the l i t e r a t u r e (see Appendix C). One proband (number 124) i n the B.C. Polydactyly study presents features of the syndrome. The d i g i t a l anomalies of some patients consist of reduction defects rather than the Polydactyly or combination of Polydactyly and hypoplasia observed i n the f i r s t ten cases. In addition Stevenson et a l . (1966) l i s t a case with imperforate anus, tracheo-oesophageal f i s t u l a , vertebral and r i b anomalies, but which isnnot noted to have malformed extremities. To eliminate the i m p l i -cation that Polydactyly i s consistently present i n t h i s syndrome perhaps i t would be convenient to speak of a caudal regression syndrome as discussed by Duhamel (1961) regarding imperforate anus deformities associated with other anomalies: most frequently vertebral anomalies, also abnormalities of the urinary t r a c t including renal agenesis, genital anomalies, malformations of the lower limbs and of the thumbs. As fa r as i s known, families of the patients are not related except for the father and four children reported by Townes & Brocks, 1970. Incidence based on the four cases with hypoplasia ascertained by Tunte (1968) i s 1.3 per 100,000, which when added to the incidence of 0.7 per 100,000 for cases with Polydactyly i n B.C. gives an estimated incidence of 2.0 per 100,000 114 l i v e born infants. Say et a l . (1971) estimate the incidence to be between . 0.007 to 0.05 per 1,000 liveborn Caucasian infants. The sex r a t i o of the patients i s 24 males : 13 females : 12 unknown. I t w i l l be i n t e r e s t i n g to see whether this 2 : 1 sex r a t i o i s maintained as additional cases are reported. Five out of ten infants died before the age of ten months and the prognosis for another c h i l d of t h i s group of ten i s reported to be poor. Chromosome studies have been done on two patients and both had a normal karyotype. P r i n c i p a l findings i n 49 possible cases are presented i n Table XXXI. There are 36 patients with a preaxial d i g i t a l defect and s i x with post-a x i a l Polydactyly (see Table XXXII). Usually one thumb i s affected. Including the group with triphalangeal duplication, 32 patients have Polydactyly and ten have rudimentary or absent d i g i t s . Three or possibly four individuals present both reduction and duplication of d i g i t s and are included i n both groups. This sample has been biased i n ascertainment of children with duplication since 12 patients were found through studies on Polydactyly. Of the 14 children ascer-tained due to the presence of anal a t r e s i a , i n the study of Tunte (1968) three had an hypoplastic or a p l a s t i c thumb(s) and one had duplicated thumbs, whereas Say et a l . (1971) found post- or preaxial Polydactyly or triphalangeal thumbs i n t h e i r nine cases. I t would appear therefore that reduction deformities are less common i n the syndrome than Polydactyly. The occurrence of both Polydactyly and reduction deformities of the d i g i t s i n the same syndrome i s not a new observation. Children whose mothers took thalidomide during the sensitive period of the pregnancy present preaxial defects ranging from aplasia to duplication as do children with syndromes believed to result from mutant genes (acrocephalopolysyndactyly, Holt-Oram syndrome and Fanconi's panmyelopathy). The preaxial anomalies of three of the luxoid mutants i n the mouse range from oligodactyly to Polydactyly and one of 115 Table XXXI. C l i n i c a l Features of the Polydactyly/imperforate Anus/ Vertebral Anomalies Syndrome Wo. of cases d i g i t a l anomalies: preaxial duplication or 48/49 reduction, occasionally postaxial Polydactyly imperforate anus: may be i n combination with 49/49 recto-perineal f i s t u l a vertebral anomalies: including increased or 17 decreased no. of vertebrae, s c o l i o s i s , b i f i d vertebrae, hemivertebrae, fused vertebral bodies r i b anomalies: including increased or decreased 12 number of r i b s , hypoplasia, fusions f a c i a l asymmetry 2 congenital heart defect 5 (? 6) c l e f t l i p and/or palate 2 tracheo-oesophageal f i s t u l a and/or oesophageal at r e s i a 7 lung abnormality 2 hypoplasia of ileum 4 aplasia of spleen " 1 u n i l a t e r a l aplasia of kidney 5 inguinal hernia5' , 2 omphalocele 1 cryptorchidism 2 congenital d i s l o c a t i o n of the hip 2 abnormality of the t i b i a , f i b u l a r or femur; s p l i t foot 3 Source: see Appendix C 116 Table XXXII. D i g i t a l Anomalies of the Polydactyly/imperforate Anus/ Vertebral Anomalies Syndrome Number of cases D i g i t a l anomaly triphalangeal thumbs, may be b i f i d U r a d i a l Polydactyly r a d i a l hypoplasia B r a d i a l Polydactyly 2 U r a d i a l polyd. & U r a d i a l hypop. U rudimentary thumb B t i b i a l polyd. & R r a d i a l polyd.* R t i b i a l polyd. & L r a d i a l hypop. L t i b i a l Polydactyly B r a d i a l aplasia U r a d i a l aplasia R rudimentary thumb & L r a d i a l abhorm. U r a d i a l abnormality B absence of radius B ulnar Polydactyly B ulnar & B f i b u l a r Polydactyly B f i b u l a r Polydactyly 2 3 1 postaxial polyd. 1 4 1 oligodactyly Number of cases radial Polydactyly 7 10 + ? 2 2 2 1* t i b i a l Polydactyly 1 1 1 radial abnormality 1 1 1 Polydactyly 1 border unknown Source: see Appendix C 117 these mutants; dominant hemimelia, also involves defects of the viscera and vertebrae (Searle, 1964). D i g i t a l defects i n dominant hemimelia are l i m i t e d to the preaxial border. To f i n d i n the P/lA/VA syndrome that d i g i t a l anomalies can be either exclu-s i v e l y postaxial or preaxial (to date there are no patients known to have both borders of the extremities affected) i s extraordinary. I t i s premature to speculate that the anomalous d i g i t a l development of both borders of the extrem-i t i e s ranging from aplasia to duplication, as well as the non-digital anomalies of the syndrome, resu l t from one s p e c i f i c dysfunction. The p o s s i b i l i t y exists that the etiology of cases with postaxial duplication i s d i f f e r e n t from that of cases with preaxial defects as appears to be true i n the association of cyclopia with Polydactyly (see p. 111). In one family (Townes & Brocks, 1970) the father and four of his s i x children have imperforate anus and triphalangeal thumbs, which i n some cases are b i f i d . At the present time i t seems most reasonable to include these individuals among cases of the polydactyly/imperforate anus/vertebral anomalies., syndrome. Inheritance would appear to be autosomal dominant i n t h i s family. In the families of two additional patients another family member with d i g i t a l defect but without other signs of the syndrome has duplication of the same border of the limbs as the patient. In one family (number 124, B.C. study) i t i s the postaxial border affected; i n the other (Puhrmann, 1968), the pre-a x i a l border. This could suggest the s i t e of the d i g i t a l anomaly associated with the syndrome i s influenced by a genetic predisposition f o r d i g i t a l defect of a given border and contributes to the predisposition. Or there may be variable expressivity of the P/lA/VA syndrome, i n which case, including a sib with imperforate anus (Puhrmann, 1968),' there would be three individuals i n the two families who present with a forme fruste. The l a t t e r interpretation 118 i s p a r t i c u l a r l y a t t r a c t i v e due to the fact that u n i l a t e r a l Polydactyly of a biphalangeal thumb i s ra r e l y noted to be a f a m i l i a l t r a i t . Laurence-Moon-Biedl syndrome. The Laurence-Moon-Biedl [UVLB] syndrome, which perhaps should more correctly be cal l e d the Bardet-Biedl syndrome, has been recognized since 1920. I t i s characterized by f i v e p r i n c i p a l abnormalities. The frequency of these f i v e characteristics found i n a study by Ammann (1970) of 57 Swiss cases i s s i m i l a r to that given by Smith (1970) whose figures are based on over 300 cases. Ammann found 45.6 fo of the patients i n his study presented with a l l of the f i v e characteristics and thus exhibited a complete form of the syndrome. D e f i n i t i o n of what constitutes a complete form varies however. Stiggelbout (1969) considers a patient who exhibits the majority of signs and i n whose sibship the missing signs occur also to be an example of the f u l l syndrome. Not infrequently, additional family emembers w i l l exhibit one or more of the c h a r a c t e r i s t i c s . A summary of the anomalies commonly seen i n patients with the LMB syndrome i s given i n Table XXXIII. In the study by Ammann (1970) supernumerary d i g i t s were found i n 38 out of 55 cases (69.1 f ° ) , and i n eight cases (14.5 f) there was isolated syndactyly or brachydactyly. Duplication affected the l e f t extremities equally often .as the r i g h t . When of the hands i t might be a fleshy pedicle, whereas supernum-erary toes were more common and were usually well developed. Duplication i s not exclusively postaxial. Occasionally the supernumerary d i g i t may involve abnormal development of the thumbs or index fingers ( B e l l , 1958). Two of the 38 patients i n Ammann's study had a b i f i d thumb. Of these two patients, one also had b i l a t e r a l f i b u l a r Polydactyly and was probably affected with the syndrome; the second patient was atyp i c a l of the syndrome i n other respects i n addition to the preaxial'duplication. Although there i s a s l i g h t excess of males reported with the syndrome (58 fo of 329 cases, B e l l , 1958), the Table XXXIII. C l i n i c a l Features of the Laurence-Moon-Biedl Syndrome Part A: Frequency by sex of the f i v e p r i n c i p a l anomalies males females t o t a l obesity 26/28 20/20 46/48 tapeto-retinal degeneration 24/28 20/20 44/48 anomalies of the extremities: 23/28 17/20 40/48 poly-, syn-, & brachydactyly mental defect 24/28 14/20 38/48 hypogenitalism 24/28 9/20 33/48 Part B: Additional anomalies* Wo. of cases progressive labyrinthine deafness 5 renal defect . 5 diabetis mellitus 5 cran i a l dysostosis 11 disorders of basal metabolism • 9 *f o r further d e t a i l s see Ammann, 1970 or Stiggelbout, 1969 Part C: Site of Polydactyly Wo. of cases both hands and both feet 10 one hand and both feet 5 both hands . 1 one hand 3 both feet 6 one foot 5 right hand and ri g h t foot 1 l e f t hand and l e f t foot 1 l e f t hand and right foot 1 extremity involved unknown 5 38 Source: Ammann, 1970 120 frequency of Polydactyly among affected males and affected females i s essentially the same ( B e l l , 1958; Ammann, 1970). D i g i t a l anomalies may be missed without X-ray examination, especially a chara c t e r i s t i c form of isolated brachydactyly which Ammann suggests i s of equivalent importance as the presence of Polydactyly or syndactyly. In the past, i t may have been f a i l u r e to detect ex i s t i n g d i g i t a l abnormalities that lead J u l i a B e l l to conclude d i g i t a l anomaly was the charact-e r i s t i c most frequently nonpenetrant. In the B.C. study one proband (number 131) and his sib presented the LMB syndrome. Correcting for the frequency of Polydactyly among affected i n d i v i -duals, t h i s suggests an incidence of approximately 0.9 per 100,000 liveborn infants over 1964 - 1967. The complex of anomalies i n the syndrome appears to be inherited i n an autosomal recessive manner. The primary defect and i t s con-comitant effects upon embryogenesis have not been determined. The fact that the toe anlagen of the f i b u l a r border are formed at a l a t e r stage than finger anlagen may be s i g n i f i c a n t i n explaining why the feet of individuals with the syndrome are more commonly and more severely affected by Polydactyly and syn-dactyly than the hands (Stiggelbout, 1969). Smith-Lemli-Opitz syndrome. Three unrelated patients with multiple con-genital anomalies who presented some of the features of the U l l r i c h - F e i c h t i g e r syndrome or Der Typus Rostockiensis were described by Smith, Lemli and Opitz i n 1964. Reports of si m i l a r cases followed and at least 31 patients have been described with Smith-Lemli-Opitz [aSLO]' syndrome (20 males and 11 females). In f i v e sibships, possibly s i x , there have been more than one affected i n d i v i -dual and i n two of these families a f i r s t cousin also presented features of the syndrome. (Smith et a l . , 1964; Pinsky & DiG-eorge, 1965; B l a i r & Martin, 1966; D a l l a i r e & Fraser, 1966; D a l l a i r e , 1969). Considering that the parents of these patients have appeared normal, t h i s f a m i l i a l tendency suggests auto-121 somal recessive inheritance. The incidence of the syndrome i s unknown. There are three cases (numbers 38, 66, 117) i n the B.C. study, however since Poly-dactyly i s not a cardinal feature the incidence of 0.02 or approximately 1 per 4,500 liveborn infants found i n th i s study i s undoubtedly low. C l i n i c a l findings i n patients with this syndrome are l i s t e d i n Table XXXIV. In addition to syndactyly (usually of the second and t h i r d toes) and f l e x i o n of the fingers, occasionally Polydactyly and reduction deformities of d i g i t s have been reported (14/31). Table XXXV presents d e t a i l s noted i n 12 cases. Supernumerary d i g i t s present i n eight cases are most l i k e l y postaxial. Two of these cases were also noted to have somewhat rudimentary thumbs, a feature found i n s i x additional cases as we l l . Radial reduction defects and ulnar Polydactyly i s also seen i n the trisomy 17-18 syndrome. I t i s inte r e s t i n g to note that triphalangism of the thumb was observed i n two reported cases of U l l r i c h - F e i c h t i g e r syndrome ( U l l r i c h , 1951). This raises the p o s s i b i l i t y that duplication as well as reduction of the thumb may be seen i n the Smith-Lemli-Opitz syndrome. Polycystic kidneys, i n t e r n a l hydrocephalus and postaxial Polydactyly. Three male sibs with polycystic kidneys, i n t e r n a l hydrocephalus and postaxial Polydactyly were reported by Simoupolis et a l . (1967). These infants died within minutes after ibirth. Chromosomal studies of the parents and t h e i r t h i r d affected infant revealed a normal karyotype, and the parents were not known to be related. A s t r i k i n g resemblance between these cases and proband number 73' and her sib has been noted (Lowry, 1971). These children presented ulnar Polydactyly, polycystic kidneys and in t e r n a l hydrocephalus (see case descriptions i n Appendix A). The second c h i l d died shortly after b i r t h whereas the proband l i v e d two years. The parents are unrelated and s i m i l a r anomalies are not known to have occurred i n either of t h e i r f a m i l i e s . 122 Table XXXIV. C l i n i c a l Features of the Smith-Lemli-Opitz Syndrome No. of cases f a i l u r e to thriv e 25/25 hypotonicity 10/23 hyp e r t o n i c i t y 12/23 microcephaly 27/28 blepharoptosis 22/27 broad nose 25/25 upturned nares 27/27 micrognathia 26/26 broad a l v e o l a r ridges 18/21 high palate 13/22 ear defect 21/22 short neck 14/14 flexed fingers 11/15 Polydactyly . 6/26 simian or bridged simian crease 19/23 pedal syndactyly 24/28 abnormal feet 16/22 hypospadias 11/18 cryptorchidism 13/18 scrotum abnormal 11/1 6 normal chromosomes 13/13 Source: Lowry et a l . , 1968; Park et a l . , 1968; Ruvalcaba et a l . , 1968; D a l l a i r e , 1969; F i n l e y et a l . , 1969; Hanissian & Summitt, 1969; S i n c l a i r et a l . , 1969 123 Table XXXV. D i g i t a l Anomalies of the Smith-Lemli-Opitz Syndrome Reference Smith et a-L (1964) Kenis & Hustinx (1967) / Kenis & Hustinx (1967) Lowry et a l . (1968) (B.C. study, case no. 66) Da l l a i r e (1969) Da l l a i r e (1969) B. C. study, case no. 38 B. C. study, case no. 117 Pinsky & DiGeorge (1965) Fine et a l . (1968) Ruvalcaba et a l . (1968) B l a i r & Martin (1966) Park et a l . (1968) Finley et a l . (1969) Sex Description of d i g i t a l anomaly M skin tag L ulnar F 6th finger L hand, postminimus off prox. phal. R hand; B short thumbs M skin tag off middle phalanx 5th finger R; short t h i r d finger B ? F extra d i g i t B ulnar F " extra biphalangeal d i g i t R ? ulnar M extra d i g i t off prox. phal. 5th toes B, uniphalangeal thumb B M extra d i g i t R ulnar M extra d i g i t s B ulnar, L f i b u l a r F "stuck on" appearance of thumb & small thenar eminence B, small f i r s t metacarpal B; small prox. phalanx great toe B M hypoplastic lowset thumb B M R thumb hypoplastic, f l a t thenar eminence B; fusion 4th and 5th metacarpals F short thumb B M short thumb B F short hallux B 124 Summary Incidence of Polydactyly i n B r i t i s h Columbia i n 1964 - 1967 was 1.02 per 1 ,000 l i v e b i r t h s . This figure includes infants with multiple congenital anomalies. Incidence was highest i n 1966 (1.35), apparently due to a greater number of ulnar cases. Parental age for the entire cohort i s simi l a r to 1964 - 1967 control figures f o r the province. However among ulnar cases unassociated with multiple congenital anomalies mean maternal and paternal age appears to • be higher f o r female probands than for male. Wo difference was detected between parity of mothers of male probands compared to female probands or compared to B.C. mothers of liveborn infants i n 1964 - 1967. Based on cases without multiple congenital anomalies, s p e c i f i c types of Polydactyly were found to have the following incidences: r a d i a l , 0.20; t i b i a l , 0.04; polysyndactyly, 0.01; ulnar, 0.32; f i b u l a r , 0.16; and ulnar-f i b u l a r , 0.09. Radial duplication i s most often u n i l a t e r a l whereas t i b i a l Polydactyly i s b i l a t e r a l . B i l a t e r a l ulnar duplication i s as frequent as u n i l a t e r a l ; u n i l a t e r a l accessory f i f t h fingers are nearly always located on the l e f t hand. Fibular Polydactyly tends to be u n i l a t e r a l . Accessory d i g i t s i n cases with both ulnar and f i b u l a r duplication are usually b i -l a t e r a l on the upper and lower limbs. Extent of duplication i s quite variable i n preaxial Polydactyly and may be triphalangeal. Among postaxial cases ulnar accessory d i g i t s tend to be rudimentary pedicles whereas f i b u l a r Polydactyly i s rarely pedicular, often syndactylous. When both ulnar and f i b u l a r Polydactyly are present the duplicated elements are usually well-formed. Genetic h i s t o r i e s indicate i n 32 families out of 138 there i s another ind i v i d u a l with Polydactyly. For,specific types of Polydactyly the follow-ing proportion of cases without multiple congenital anomalies had a posi-tiv e family history: r a d i a l , 5 - 19 t i b i a l , 0 fo; ulnar, 29 %; f i b u l a r , 125 25 f; and ul n a r - f i b u l a r , 73 f. Transmittance of postaxial Polydactyly by unaffected parents with a history of accessory d i g i t s i s more common among females, and more common for ulnar and f i b u l a r types of Polydactyly. Non-penetrance of gene.('s) for u l n a r - f i b u l a r Polydactyly i s unknown among males. Polygenic inheritance of ulnar and of f i b u l a r types of Polydactyly i s suggested by the finding that the percentage of affected sibs i s greater when there i s a history of Polydactyly i n previous generations (approximately. 6.6 fo) than for probands with a negative history ( 1 . 2 fo). The number of affected sibs of the probands (3/107) i s i n agreement with the number which would be expected for a polygenic t r a i t . Data for u l n a r - f i b u l a r Polydactyly i s more ccompatible with dominant inheritance with reduced penetrance among females. F i f t y percent of the offspring of polydactylous males were affected; a smaller percentage of the children of affected mothers were polydactylous. Among ul n a r - f i b u l a r cases with no history of accessory d i g i t s i n previous generations, 17.4 f of the sibs were polydactylous. The occurence of minor anomaly or a single major anomaly among polydactylous infants does not appear to be much greater than would be seen among infants with a given minor anomaly. However multiple major anomalies are 25 times more frequent. A polydactylous c h i l d found to have one major malformation i s twice as l i k e l y to have additional major anomalies than a c h i l d with one major anomaly who has the normal number of d i g i t s . Multiple congenital anomalies were most commonly seen with u l n a r - f i b u l a r Polydactyly, and 60 fo of the children with more completely formed accessory d i g i t s of th i s type had multiple malformations. This may r e f l e c t the fact that u l n a r - f i b u l a r duplication i s the type most commonly seen as a feature of various syndromes. 126 L i t e r a t u r e C i t e d Aase, J . M., and Smith, D. ¥. 1969. Congenital anemia and t r i p h a l a n g e a l thumbs: a new syndrome. J . Pe d i a t . 74:471-4. Ahl.feld 1880. Missbildungen des Mensehen P. 106. L e i p z i g . ( C i t e d by Lewis, 1909.) A l b r e c h t 1886. Centrabl. f. C h i r . 24:suppl.:105. ( C i t e d by Lewis, 1909.) Ammann, F. 1970. I n v e s t i g a t i o n s c l i n i q u e s et genetiques sur l e syndrome de Ba r d e t - B i e d l en Suisse. J . Genet. Hum. 18:suppl. Annahdale, T. 1865. The Malformations, Diseases and I n j u r i e s of the Fingers and Toes. Edinburgh. ( C i t e d by Cummins, 1932.) Ashby, D. ¥., Chadha, J . S., and Henderson, C. B. 1969. As s o c i a t e d s k e l e t a l and c a r d i a c a b n o r m a l i t i e s : the Holt-Oram syndrome. Quart. J . Med. 38:267-76. A t k i n s , L., and Rosenthal, ¥. K. 1961. M u l t i p l e c o n g e n i t a l a b n o r m a l i t i e s a s s o c i a t e d w i t h chromosomal trisomy. New Eng. J . Med. 265:314-8. At k i n s o n , S. B. 1901. Some cases of P o l y d a c t y l y and syndactyly o c c u r r i n g i n one f a m i l y . S t . B a r t s . Hosp. J . 8:169-. ( C i t e d by B e l l , 1953.) A t t l e e , ¥. H. ¥. 1907. A.case of supernumerary d i g i t s . Lancet 2:163. Atwood, E. S., and Pond, C. P. 1917. A-polydactylous f a m i l y . J . Hered. 8:96. B a l l o w i t z , E. 1904. Uber hyperdaktyle F a m i l i e n und d i e Vererbung der V i e l -f i n g e r i g k e i t des Mensehen. Arch. Rassen- G e s e l l s c h . - B i o l . 1:347-65. ( C i t e d by Gates, 1946.) Ba r r e r , L. A. 1947. U n i l a t e r a l hexadactyly i n man. J . Hered. 38:345-6. Barsky, A. J . 1958. Congenital Anomalies' of the Hand and The i r S u r g i c a l Treatment. S p r i n g f i e l d , 111.: Charles C. Thomas. Bass, H. N. 1968. F a m i l i a l absence of middle phalanges w i t h n a i l d y s p l a s i a : a new syndrome. P e d i a t r i c s 42:318-23. Bates,'D. 1966. The Passing of the A b o r i g i n e s . 2d. ed., p. 121. London: John Murray L t d . Bateson, ¥. 1909. Mendel's P r i n c i p l e s of Heredity. P. 228. Cambridge: U n i v e r s i t y Press. B e l l , J . 1930. Some new pedigrees of h e r e d i t a r y disease. A. P o l y d a c t y l i s m and syndactylism. B. Blue s c l e r o t i c s and f r a g i l i t y of bone. Ann. Eugen. 4:41-8. . 1953. On syndactyly and i t s a s s o c i a t i o n w i t h P o l y d a c t y l y . In The Treasury of Human In h e r i t a n c e . Ed. L. S. Penrose, v o l . 5> p t . 2, pp. 33-50. Cambridge: U n i v e r s i t y Press. 127 B e l l , J. 1958. The Laurence-Moon syndrome. In The Treasury of Human Inheritance. Ed. L. S. Penrose, v o l . 5, p't. 3, pp. 51-96. Cambridge: Univ e r s i t y Press. Benady, S. G., and Harris, R. J . 1969. Trisomy 17-18. A study of f i v e cases, three of whom were associated with oesophageal a t r e s i a . Acta Paediat. Scand. 58:445-8. Bi b l e . The Holy Bible, King James Version. Cleveland and New York: The World Publishing Co. Bick, E. M. 1960. Congenital deformities of the musculoskeletal system noted i i n the newborn. Amer. J. Dis. C h i l d . 100:861-8. B l a i r , H. R., and.Martin, J . K. 1966. A syndrome characterized by mental retardation, short stature, c r a n i o f a c i a l dysplasia and g e n i t a l anomalies occurring i n s i b l i n g s . J . Pediat. 69:457-9. Blanck, C , J a i l i n g , B., Lindsten, J . , and Z e t t e r q v i s t , P. 1964. Trisomy 13-15; Report of a case with c l i n i c a l , cytogenetic and pathologic findings. Acta Path. M i c r o b i o l . Scand. 60:36-46. Boinet, E. 1898. P o l y d a c t y l i e et atavisme. Rev. de Med., Paris 18:316-28. (Cited by B e l l , 1930.) Book, J . A. 1951. The incidence of congenital diseases and defects i n a South Swedish population. Acta Genet. 2:289-311. Bowen, P., Lee, C. S. H., Shea, D. R., and Armstrong, H. B. 1970. Polydactyly and other minor stigmata associated with 46,XX/47,XX,D+ mosaicism. Canad. Med. Ass. J . 102:49-51. Boyd, J. D., and M i l l e s , A. E. 1951. An erupted tooth i n a cyclops foetus. B r i t . Dent. J. 91:173-81. Brandeis, J . W. 1915. Polydactylism as a hereditary character. J.A.M.A. 64:1640-2. Brodie, H. R., and D a l l a i r e , L. 1962. The E syndrome (trisomy 17-18) r e s u l t i n g from a maternal chromosomal t r a n s l o c a t i o n . Cand. Med. Ass. J . 87:559-61. Buhler, E., Bodis, I., Rossier, R., and Stalder, G. 1962. Trisomie 13-15 mit cebocephalie. Ann. Paediat. (Basel) 199:198-205. Bunnell,. S. 19-56. Surgery of the Hand. 3d. ecL, pp. 936-7. Phi l a d e l p h i a and Montreal: J . B. L i p p i n c o t t Co. Burks, J . L., and, Sinkford, S. 1964. C l i n i c a l trisomy E.syndrome (16-18): a cytogenetic enigma. C l i n . Pediat. (Phila.) 3:233-5. Butomo, I. If., and Shushval, 0. H. 1968. Mnozhestvennye vrozhdennye urodstva u novorozh-dennogo, svyazannye s trisomeie D^  i t r a n s l o k a t s i e i D/D. [Multiple congenital anomalies i n a newborn associated with the trisomy D and the t r a n s l o c a t i o n D/D.]' Genetika 4:161-5. (Engl, summary: B i o l . Abst., v o l . 50, p. 10654, no. 110223, 1969.) 128 Callan, R. 1942. Polydactyly i n a Negro family. J . Hered. 33:229-32. Canada. Dominion Bureau of S t a t i s t i c s . Catalogue 92-553, 1961 Census of Canada; seri e s 1.3-2, Population: Ethnic groups by age groups. C a r l i , J . , and Torre, P. X. 1961. Un cas d e c y c l o p i e . Ann. O c u l i s t (Paris) 194:870-80. C a r l i s l e , A. 1814. An accouhit of a family having hands and f e e t with super-numerary fingers and toes. P h i l . Trans. Roy. Soc. 104:94-101. (Cited by Gates, 1946.) Carter, C. 0. 1969. An ABC of Medical Genetics. VI. Polygenic inheritance and common diseases. Lancet 1:1252-6. Chapman, K. 1936. Human cyc l o p i a . Arch. Ophthal. (Chicago) 16:40-5. Chesler, E., Preiman, I., Rosen, E., and Wilton, E. 1970. Congenital aneurysm of the membranous v e n t r i c u l a r septum associated with p a r t i a l trisomy E syndrome. Amer. Heart J . 79:805-10. Chung, C. S., and Myrianthopoulos, N. C. 1968. R a c i a l and prenatal f a c t o r s i n major congenital malformations. Amer. J . Hum. Genet. 20:44-60. Cohen, M. M. 1966. Chromosomal mosaicism associated with a case of c y c l o p i a . J . Pediat. 69:793-8. Conn, I. 1932. S k e l e t a l disturbances and anomalies: c l i n i c a l reports and review of l i t e r a t u r e . Radiology 18:592-626. Crawfurd, M. d''A. 1961. M u l t i p l e congenital anomaly associated with an extra autosome. Lancet 2:22-4. Cummins, H. 1932. Spontaneous amputation of human supernumerary d i g i t s ; pedunculated postminimi. Amer. J . Anat. 51:381-416. D a l l a i r e , L. 1969. Syndrome of r e t a r d a t i o n with urogenital and s k e l e t a l anomalies (Smith-Lemli-Opitz syndrome): c l i n i c a l features and mode of inheritance. J . Med. Genet. 6:113-20. D a l l a i r e , L., and Fraser, F. C. 1966. The syndrome of r e t a r d a t i o n with urogenital and s k e l e t a l anomalies i n s i b l i n g s . J . Pediat. 69:459-60. Danforth, C. H. 1919. A comparison of the hands of a p a i r of polydactyl Negro twins. Amer. J . Phys. Anthrop. (Wash.) 2:147-65. Dehus, D., and Snyder, L. H. 1932. Dominance i n man, with especial reference to polydactylism. Ohio J . S c i . 32:232-6. (Cited by Gates, 1946.) De Linares, L. G. 1930. C o l l e c t i v e polydactylism i n a small town;•lecture quoted by Madrid correspondent. J.A.M.A. 94:2080-1. De Marinis, F., and Sobbota, A. 1957. On the inheritance and development of p r e a x i a l and p o s t a x i a l types of Polydactyly. Acta Genet. (Basel) 7:215-6. 129 Devay 1863. Arch. Gen. de Med. 1:763. (Cited by Lewis, 1909.) Digby, K. 1645. Immortality of Reasonable Souls. Ch. 23, p. 265. London. (Cited by Z i r k l e , 1936.) Down, J. L. H. 1.866. Observations on an ethnic c l a s s i f i c a t i o n of i d i o t s . C l i n . Lect. Rep. London Hosp. 3:259-. Duhamel, B. 1961. Prom the mermaid to anal imperforation: the syndrome of caudal regression. Arch. Dis. C h i l d . 36:152-5. Durlacher 1915. Zur K a s u i s t i k der Zyklopie mit Russelbildung. Deutsch. Med. Wschr. 41:1128-9. Ecke, H. 1962. Beitrag zu den Doppelmissbildungen im Bereich der Finger. Bruns B e i t s . K l i n . Chir. 205:463-8. (Cited by Temtamy, 1966b.) Edwards, J . H. 1960. The simulation of mendelism. Acta Genet. (Basel) 10:63-70. . 1969. F a m i l i a l p r e d i s p o s i t i o n i n man. B r i t . Med. B u l l . 25:58-64. Edwards, J . H., Harden, D. G., Cameron, A. H., Crosse, V. M., and Wolf, 0. H. 1960. A new trisomic syndrome. Lancet 1:787-90. Egawa, T. 1971. Personal communication. Egawa, T., Doi, T., Yoshioka, Y., and Hiroshima, K. 1969. Polydactyly of the foot. Jap. J . P l a s t . Reconstr. Surg. 12:363-8. Ehrat, R. 1948. Die Missbildungen der Neugeborenen an der Univ e r s i t a t s f r a u e n K l i n i k Zurich 1921-1944.. Zurich: V i l l i g e r and Cie. (Cited by Heel, 1958.) E l l i s , J . R., and Marwood, J . C. 1961. Autosomal trisomy syndromes. Lancet 2:263. E l l i s , R. 1866. On a rare form of twin monstrosity. Obstet. Soc. of London Trans. 29:160-4. Fabia, J . , and Drolette, M. 1970. Malformations and leukemia i n c h i l d r e n with Down's syndrome. P e d i a t r i c s 45:60-70. Faint, S., and Lewis, F. J . W. 1964. Presumptive d e l e t i o n of the short arm of chromosome 18 i n a cyclops. Human Chrom. Newsl. No. 14, pp. 5-6. Farabee, W. C. 1903. Hereditary and Sexual Influence i n M e r i s t i c V a r i a t i o n . A.study of d i g i t a l malformations i n man. Ph.D. d i s s e r t a t i o n , Harvard U n i v e r s i t y . Fine, R. N., Gwinn, J . L., and Young, E. F. 1968. Smith-Lemli-Opitz syndrome. Radiologic and postmortem fi n d i n g s . Amer. J . Dis. C h i l d . 115:483-8. F i n l e y , W. H., F i n l e y , S. C , and Carte, E. T. 1963. 17-18 trisomy syndrome; review, and report of a case. Amer. J . Dis. C h i l d . 106:591-6. 130 Finley, S. C, Finley, ¥. H., and Monsky, D. B. 1969. Cataracts i n a g i r l with features of the Smith-Lemli-Opitz syndrome. J. Pediat. 75:706-7. Fitzgerald, M., and Heal, B. 1964. Personal communication. Frazier, T. M. 1960. A note on race-specific congenital malformation rates. Amer. J. Obstet. Gynec. 80:184-5. Fuhrmann, W. 1968. A new polydactyly/imperforate anus/vertebral-anomalies syndrome. Lancet 2:918-9. G a l l , J. C, J r . , Stern, A. M., Cohen, M. M., Adams, M. S., and Davidson, R. T. 1966. Holt-Oram syndrome: c l i n i c a l and genetic study of a large family. Amer. J. Hum. Genet. 18:187-200. Gates, R. R. 1946. Human Genetics, Vol. 1, pp. 415-39. ; Hew York: Macmillan Co. German, J. L., 3d., Rankin, J. K., Harrison, P. A., Donovan, D. J . , Hogan, W. J . , and Beam, A. G. 1962. Autosomal trisomy of a group 16-18 chromosome. J. Pediat. 60:503-12. Gibson, R. 1961. Pelizaeus-Merzbacher's disease. Canad. Med. Ass. J. 85:820-3. Goodman, R. M. 1965. A family with polysyndactyly and other anomalies. J. Hered. 56:37-8. Gorlin, R. J.; and Pindborg, J. J. 1964. Syndromes of ib'he Head and Heck. Pp. 179, 349-50. Hew York, Toronto and London: McGraw-Hill. Gottlieb, M. I., Hirschhorn, K., Cooper, H. L., Lusskin, H., Moloshok, R. E., and Hodes, H. L: 1962. Trisomy-17 syndrome. Report of three cases and review of the l i t e r a t u r e . Amer. J. Med. 33:763-73. Gray, D. J . , Gardner, E., and O'Rahilly, R. 1957. The prenatal development of the skeleton and j o i n t s of the human hand. Amer. J. Anat. 101:169-202. Grosse, F. R., Herrmann, J., and Opitz, J. M. 1969. The F-form of acro-pectoro-vertebral dysplasia: The F syndrome. In C l i n i c a l Delineation of B i r t h Defects, 1st conf. B i r t h Defects: Original A r t i c l e Series, v o l . 5, pt. 3, Limb Malformations, ed. D. Bergsma, pp. 48-63. [Hew York]: The Hational Foundation-March of Dimes. Gupta, B. 1969. Incidence of congenital malformations i n Higerian children. ¥. Afr. Med. J. 18:22-7. Haas, S. L. 1939. Three-phalangeal thumbs. Amer. J. Roentgen. 42:677-82. H a l l , B. 1964. Mongolism i n newborns. A c l i n i c a l and cytogenetic study. Acta Paediat. Scand. Suppl. 154. Handforth, J. R. 1950. Polydactylism of the hand i n southern Chinese. Anat. Rec. 106:119-25. Hanissian, A. S., and Summitt, R. L. 1969. Smith-Lemli-Opitz syndrome i n a Hegro c h i l d . J. Pediat. 74:303-5. 13:1 Hansen, H. G., Tolksdorf, M., Zinat-Bakhsh, H., Lehmann, ¥., Kitsch, K., and Wiedemann, H. R. 1963. Malformation syndrome with trisomy .amongst the chromosomes of the group 16-18. Human Chrom. Newsl. Wo. 9, p. 12. Haylock, H., Fitzgerald, M., Danks, D., and Dennett, X. 1963. Personal communication. Hecht, P., Bryant, J. S., Motulsky, A. G., and Gilbert, E . R. 1963. The no. 17-18 (E) trisomy syndrome. Studies on cytogenetics, dermatoglyphics, paternal age and linkage. J. Pediat. 63:605-21. Hefner, R. A. 1940. Hereditary Polydactyly associated with extra phalanges in the thumbs. J. Hered. 31:25-7. Holman, G. H., Erkman, B., Zacharias, D. L., and Kock, H. P. 1963. The 18-trisomy syndrome two new c l i n i c a l variants. One with associated tracheo-oesophageal f i s t u l a and the other with probable familial occurrence. Hew Eng. J. Med. 268:982-8. Holt, M., and Oram, S. 1960. Familial heart disease with skeletal malformations. Brit. Heart J. 22:236-42. Hook, E. B., Lehrke, R., Roesner, A., and Yunis, J. J. 1965. Trisomy-18 i n a 15-year-old female. Lancet 2:910-1. Hook, E. B., and Petry, J. J. 1970. Single hit aetiology of human minor con-genital malformations unassociated with major congenital malformations. Nature (London) 227:847-8. Hook, E. B., and Yunis, J. J. 1965. Trisomy 18-syndrome i n a'patient with a normal karyotype, c l i n i c a l and dermatoglyphic findings. J.A.M.A. 193:840-3. Jackson, V. W. 1937. Pour generations of Polydactyly. J. Hered. 28:267-8. James, A. E., Jr., Belcourt, C. L., Atkins, L., and Janower, M. L. 1969. Trisomy 13-15. Radiology 92:44-9. James, J. I. P., and Lamb, D. W. 1963. Congenital abnormalities of the limbs. Practitioner 191:159-72. Jenness, D. 1955. The Indians of Canada. 3d. ed., Bull?^.65|"Anthropological Series No. 15, pp. 233-48. Ottawa: Queen's Printer. Joachimsthal, G. 1900. Berlin. Klin. Wschr. 37:835-. (Cited by Lapidus, Guidotti and Coletti, 1943,) Johnston, 0., and Davis, R. W. 1953. On the inheritance of hand and foot anomalies i n six families. Amer. J. Hum. Genet. 5:356-72. Kanavel, A. B. 1932. Congenital malformations of the hands. Arch. Surg. 25:1-53,282-320. Kaufman, R. L., Quinton, B., and Ternberg,' J. L. 1970. Polydactyly/imperforate anus/vertebral anomalies syndrome. Lancet 1:841. 132 Kenis, H., and Hustinx, W. J . 1967. A f a m i l i a l syndrome of mental retardation i n a s s o c i a t i o n with multiple congenital anomalies resembling the syndrome of Smith-Lemli-Opitz. Maandschr. Kindergeneesk. 35:37-48. Koenig, E. U., Lubs, H. A., J r . , and Brandt, I. K. 1962. A r e l a t i o n s h i p between congenital anomalies and autosomal chromosome abnormalities. Yale J . B i o l . Med. 35:189-205. Kolah, P. J . , Master, P. A., and Sanghvi, L. D. 1967. Congenital malformations and p e r i n a t a l m o r t a l i t y i n Bombay. Amer. J . Obstet. Gynec. 97:400-6. Zraus, B. S. 1961 . Sequence of appearance of primary centers of o s s i f i c a t i o n i n the human foot. Amer. ,J. Anat. 109:103-15. Lafourcade, J . , Bocquet, L., C r u v e i l l e r , J . , Saraux, H., Berger, R., Lejeune, J . , Huet de Barochez, Y., and Turpin, R. 1964. Aberrations chromosomiques et maladies humaines. Contribution a 1'etude anatomique de l a trisomie 13. B u l l . Soc. Med. Hop. Paris 115:383-99-Lapidus, P. ¥.,and Gu i d o t t i , F. P. 1944. Triphalangeal b i f i d thumb: report of s i x cases. Arch. Surg. 49:228-34. Lapidus, P. ¥., G u i d o t t i , F. P., and C o l e t t i , C. J . 1943- Triphalangeal thumb: report of s i x cases. Surg. Gynec. Obstet. 77:178-86. Lejeune, J . , Gauthier, M., and Turpin, R. 1959. Les chromosomes humains en culture de t i s s u s . C. R. Acad. S c i . [D] (Paris) 248:602-. Lenglen 1877. Sur l a p o l y d a c t y l i e h e r e d i t a i r e . B u l l . Acad. Med. 6:1312-4. (Cited by B e l l , 1953.) Lenz, ¥. [1964]. Chemicals and malformation i n man. In International Conference on Congenital Malformations, 2d., New York, 1963. Congenital Malformations. Ed. In t e r n a t i o n a l Medical Congress, pp. 163-76. New York: International Medical Congress. - . 1965. Epidemiology of congenital malformations. Ann. N. Y. Acad. S c i . 123:228-36. . 1966. Malformations caused by drugs i n pregnancy. Amer. J. Dis. C h i l d . 112:99-106. . 1969. Bone defects of the limbs an overview. In Conference on the C l i n i c a l Delineation of B i r t h Defects, 1st. B i r t h Defects: O r i g i n a l A r t i c l e Series, v o l . 5, pt. 3, Limb Malformations, ed. D. Bergsma, pp. 1-6. New York: The National Foundation-March of Dimes. Levkoff, A. H., Mather, G. B., and E i s e n s t e i n , R. P. 1964. A case of trisomy 16-18 syndrome. Speculation on pathogenesis of chromosome-induced malfor-mations. Amer. J . Dis. C h i l d . 107:300-3. Lewis, A. J . 1964. The pathology of 18 trisomy. J . Pediat. 65:92-101. Lewis, F. J . ¥., and Faint, S. 1965- Trisomies of D 13-15 and E 1.7-18: two cases. Human Chrom. Newsl. No. 15, pp. 12-4. 133 Lewis, T. 1909. Polydactylism. In The Treasury of Human Inheritance. Vol. 1, pt. 1, pp. 10-4. London: Dulau and Co. Lineback, P. E. 1921. A case of u n i l a t e r a l Polydactyly i n a 22-mm embryo. Anat. Rec. 20:313-9. Lowry, R. B. 1971. Personal communication. Lowry, R. B., M i l l e r , J. R., and MacLean, J. R. 1968. Micrognathia, Polydactyly, and c l e f t palate. J . Pediat. 72:859-61. Lubs, H. A., J r . , Koenig, E. IT., and Brandt, I. K. 1961. Trisomy 13-15, a c l i n i c a l syndrome. Lancet 2:1001-2. Lticker, P. C. 1924. Uber Vererbung von Missbildungen, insbesondere Hasenscharte und Polydaktylie, und ihre Beziehungen zur Geburtshilfe. Mschr. P. Geburtsh. u. Gynak. 66:327-36. (Cited by Gates, 1946.) McClintic, B. S. 1935- Five generations of polydactylism. J . Hered. 26:141-4. Mcintosh, R., M e r r i t t , K. K., Richards, M. R., Samuels, M. H., and Bellows, M. T. 1954. The incidence of congenital malformations: a study of 5,964 pregnancies. Pediatrics 14:505-22. McKellar, P. H. M. 1870. Hereditary malformation of extremities. Glasgow Med. J. N. S. 2:390-1. (Cited by B e l l , 1930.)-McKeown, T. [1961J. Sources of va r i a t i o n i n the incidence of malformations. In International Conference on Congenital Malformations, 1st., London, 1960. Congenital Malformations. Ed. [M. Fishbein] f o r the International Medical Congress, Ltd., p. 4 6 . Philadelphia: J . B. Lippincott Co. McKusick, V. !£. 1961. Medical genetics 1960. J. Chronic Dis. 14:38. .i 1969. Human Genetics. Foundations of Modern Genetics Series, ed. S. R. Suskind and P. E. Hartman, 2d., ed., p. 194. New Jersey: Prentice-H a l l , Inc. Magenis, R. E., Hecht, P., and Milham, S., J r . 1968. Trisomy 13 (D. ) syndrome: studies on parental age, sex r a t i o , and su r v i v a l . J . Pediat. 73:222-8. M a l l , P. P. 1906. On o s s i f i c a t i o n centers i n human embryos less than 100 days old. Amer. J. Anat. 5:433-58. Manoiloff, E. 0. 1931. A rare case of hereditary hexadactylism. Amer. J . Phys. Anthrop. 15:503-8. Marden, P. M., Smith, D. ¥., and McDonald, M. J . 1964. Congenital anomalies i n the newborn infant, including minor variations. J. Pediat. 64:357-71 . Marin-Padilla, M., Hoefnagel, D., and' Benirschke, K. 1964. Anatomic and h i s t o -pathologic study of two cases of D -(13-15) trisomy. Cytogenetics (Basel) 3:258-84. Mathew, P. ¥. 1908. A case of hereditary brachydactyly. B r i t . Med. J . 2:969. 134 Mehes, K., and Bata, G. 1 9 6 5 . Congenital thrombocytopenia i n 1 3 - 1 5 trisomy. Lancet 1 : 1 2 7 9 . M e l l i n , G. ¥. 1 9 6 3 . The frequency of b i r t h defects. In B i r t h Defects, ed. M. Fishbein, pp. 1 - 1 7 . Philadelphia and Montreal: Lippincott. M i l l a r d , M. 1 9 6 9 . The polydactyly/imperforate-anus/vertebral anomalies syndrome. Lancet 1 : 1 5 6 . M i l l e r , J. Q . , Picard, E. H., Alkan, M. K., Warner, S., and Gerald, P. S. 1 9 6 3 . A s p e c i f i c congenital brain defect (arhinencephaly) i n 1 3 - 1 5 trisomy. New Eng. J. Med., 2 6 8 : 1 2 0 - 4 . M i l l e s , B. L. 1 9 2 8 . The inheritance of human sk e l e t a l anomalies. J. Hered. 1 9 : 2 8 - 4 6 . M i l l e s i , H. 1 9 6 7 . Deformations of the fingers following operations for polydactylia. .Klin. Med. (Wien) 2 2 : 2 6 6 - . (Cited by Wassel, 1 9 6 9 . ) Mitani, S. 1 9 4 3 . Malformations of newborns. Sanka to Fujinka 1 1 : 3 4 5 - 5 6 . (Cited by Neel, 1 9 5 8 . ) Mohan, J. 1 9 6 9 . Postaxial Polydactyly i n three Indian fa m i l i e s . J. Med. Genet. 6 : 1 9 6 - 2 0 0 0 Mottet, N. K., and Jensen, H. 1 9 6 5 . The anomalous embryonic development associated with trisomy 1 3 - 1 5 . Amer. J. C l i n . Path. 4 3 : 3 3 4 - 4 7 . Mueller, W. 1 9 3 6 . Beitrage zur Kenntnis des "dreigliedrigen Daumens. Arch. K l i n . Chir. 1 8 5 : 3 7 7 - 8 6 . (Cited by Lapidus, Guidotti and C o l e t t i , 1 9 4 3 . ) Neel, J. V. 1 9 5 8 . A.study of major congenital defects i n Japanese infants. Amer. J. Hum. Genet. 1 0 : 3 9 8 - 4 4 5 . Heel, J. V, and Rusk;i M. L. 1 9 6 3 . Polydactyly of the second metatarsal with associated defects of the feet: a new, simply inherited s k e l e t a l deformity. Amer. J. Hum. Genet. 1 5 : 2 8 8 - 9 1 . Nishimura, H. 1 9 7 0 . Incidence of malformations i n abortions. In International Conference on Congenital Malformations; 3 d . , The Hague, 1 9 6 9 . Congenital Malformations. Ed. F. C. Fraser and V. A. McKusick, pp. 2 7 5 - 8 3 . Amsterdam and New York: Excerpta Medica. Nishimura, Hi., Takano, K., Tanimura, T., Yasuda, M., and Uchida, T. 1 9 6 6 . High incidence of several malformations i n the early human embryos as compared with infants. B i o l . Neonat. 1 0 : 9 3 - 1 0 7 . Nishimura, H., and Yamamura, H. 1 9 6 9 . Comparison between . mian and some other mammals of normal and abnormal developmental processes. In International Workshop i n Teratology, 2 d „ Kyoto, 1 9 6 8 . Methods for Teratological Studies i n Experimental Animals and Man; Proceedings. Ed. H. Nishimura and J. R. M i l l e r , pp. 2 2 3 - 4 0 . Tokyo: Igaku Shoin. 135 Nishimura, H., and Yasuda, Y. 1969. Culture of human and mouse limb-buds as a tool for testing the embryotoxicity of drugs. In International Workshop i n Teratology, 2d., Kyoto, 1968. Methods for Teratological Studies i n Experimental Animals and Man; Proceedings. Ed. H. Nishimura and J. R. M i l l e r , pp. 272-3. Tokyo: Igaku Shoin. Nitowsky, H. M., Sindhvandanda, N., Konigsberg, U. R., and Weinberg, T. 1966. P a r t i a l 18 monosomy i n the cyclops malformation. Pediatrics 37:260-9. Northcutt, R. C. 1962. Multiple congenital anomalies i n a Negro infant with 13-15 trisomy. Southern Med. J. 55:385-9. (Cited by Smith et a l . , 1963.) Odrione, J. M. 1943. Polydactylism i n related New England fam i l i e s . J . Hered. 34:45-55. Oliver, C. P. 1940. Recessive polydactylism associated with mental deficiency. J. Hered. 31:365-7. Orel, H. 1928. Kleine Beitrage zur Vererbungswissen-schaft. Zeits. f. Konst-lehre 13:691-8. (Cited by Gates, 1946.) Park, S. C., Needles, C. P., Dimich, I., and Sussman, L. 1968. Congenital heart disease i n an infant with the Smith-Lemli-Opitz syndrome. J. Pediat. 73:896-902. Patau, K., Therman, E., Smith, D. W., and Inhorn, S. L. 1961. Two new cases of trisomy i n man. Hereditas 47:239-42. Patau, K., Smith, D. W., Therman, E., Inhorn, S. L., and Wagner, H. P. 1960,. Multiple congenital anomaly caused by an extra autosome. Lancet 1:790-3. Penhallow, D. P. 1928. An unusual case of polydactylism. J.A.M.A. 91:564-5. Penrose, L. S. 1933. The r e l a t i v e effects of paternal and maternal age i n mongolism. J. Genet. 27:219-24. P f e i f f e r , R. A. 1964. Personal communication. P f i t z e r , P., and Muntefering, H. 1968. Cyclopism as a hereditary malformation. Nature (London) 217:1071-2. Pf i t z n e r , W. 1898. Beitrage zur Kenntniss der Missbildungen des menschlichen Extremitatenskelets. Morph. Arbeit. 8:304-40. (Cited by B e l l , 1953.) Pinsky, L., and DiGeorge, A. M. 1965. A f a m i l i a l syndrome of f a c i a l and sk e l e t a l anomalies associated with geni t a l abnormality i n the male and normal genitals i n the female. J. Pediat. 66:1049-54. Pipkin, S. B., and Pipkin, A. C. 1946. Variation of expression of Polydactyly. J. Hered. 37:93-96. Pl i n y , C. 1476. Naturalis H i s t o r i a . Prom Lib. XI., cap. 43 e n t i t l e d " D i f f e r e n t i a membrorum hominis a coeteris animalibus". Parmal. (Cited by B e l l , 1930.) Ploucquet "Obs. medicar pentas", i n Nov. Act. 'Nat. Cur.' 8:26. (Cited by E l l i s , 1866.) 4.36 Pott, R. 1884. Ein Beitrag zu den symmetrischen Missbildungen der Finger und Zehen. Jahrb. Kinderheilk. 21:392-. (Cited by Temtamy, 1966b.) Potter, E. L. 1952. Pathology of the Fetus and the Newborn. Pp. 418-23. Chicago: The Year Book Publishers, Inc. Powars, D., Rohde, R., and Graves, D. 1964. Foetal haemoglobin and neutrophil anomaly i n the D^-trisomy syndrome. Lancet 1:1363-4. Qazi, Q. H., and Smithwick, E. M. 1970. Triphalangy of thumbs and. great toes. Amer. J. Dis. Child. 120:255-7. Reid, R. L., and Woolf, C. M. 1970. A .genetic and karyotype study of complete or incomplete paraxial radial hemimelia i n Arizona implications for genetic counseling.. Arizona Med. 27:6-11. Reider, H. 1900. Eine Familie mit dreigliedrigen Daumen. Zeitsch. f. Morph. und Anthrop. 2:177-97. (Cited by Farabee, 1903.)-Robinson, G. C , Miller, J. R., and Bensimon, J. R. 1962. Familial ectodermal dysplasia with sensori-neural deafness and other anomalies. Pediatrics 30:797-802. Rohde, R. A., Hodgman, J. E., and Cleland, R. S. 1964. Multiple congenital anomalies i n the E^-trisomy group (16-18) syndrome. Pediatrics 33:258-70. Rohde, R. A., Lee, A., and Sapin, S. 1963. A new trisomy-translocation chromosome (long-arm E/E). Lancet 2:1509-10. Rosenfield, R. L., Breibart, S., Isaacs, H., Klevit, H.D., and Mellman, W. J. 1962. Trisomy of chromosome 13-15 and 17-18: i t s association with infantile arteriosclerosis. Amer. J. Med. Sci. 244:763-79. Rudert, I. 1938. liber die Vererblichkei.t der praaxialen Polydaktylie. Zeits. f. Konst-lehre 21-.545-57. (Cited by Gates, 1946.) Ruvalcaba, R. H. A., Reichert, S., and Smith, D. W. 1968. Smith-Lemli-Opitz syndrome. Case report. Arch. Dis. Child. 43:620-3. Rysanek, M. 1960. Zyklopie. Zbl. Gynaek. 82:677-80. Saldanha, P. H. [1964]. Frequency of congenital malformations i n mixed populations of southern Brazil. In International Conference on Congenital Malformations, 2d, New York, 1963. Congenital Malformations. Ed. International Medical Congress, Ltd, pp. 323-33. New York: The Inter-national Medical Congress. Salzano, F. M. 1961. Rare genetic conditions among the Caingang Indians. Ann Hum. Genet. 25:123-30. Salzer, M. 1960. Tiber den kongenitalen Tibiadefekt. Zbl. Chir. 85:673-81 . Sarma, V. 1963. Ocular abnormalities of the foetus with special reference to cyclopia. Brit. J. Ophthal. 47:193-202. / 07. Say, B., B a l c i , S., Pirnar, T., and Tuncbilek, E. 1971. A new syndrome of dysmorphogenesis: imperforate-anus associated with poly-, oligodactyly and s k e l e t a l (mainly vertebral). anomalies. Acta Paediat. Scand. 60:197-202. Say, B., and Gerald, P. S. 1968. A .new polydactyly/imperforate anus/vertebral anomalies syndrome. Lancet 2:688. Schinz, H.; Baench, ¥. E.; Priedle, E.; and Uehlinger, E. 1951. Roentgen-Diagnostics. Ed. J. T. Case, v o l . -1, pt. 1, Skeleton, pp. 765-83. New York: Grune and Stratton. Searle, A. G. 1964. The genetics.and morphology of two "luxoid" mutants i n the house mouse. Genet. Res. 5:171-97. Sedano, H. 0., and Gorlin, R. J. 1963. The oral manifestations of cyclopia. Review of the! l i t e r a t u r e and report of two cases. Oral Surg. 16:823-38. Sedgwick, A. 1863. (Cited by Gates, 1946.) Sergovich, P., Madronich, J. S., Barr, M.L., Carr, D. H., and Langdon, ¥. A. 1963. The D trisomy syndrome: a case report with a description of ocular pathology. Canad. Med. Ass. J. 89:151-7. Shevkenek, ¥., and Thompson, ¥. P. 1933. A case of recessive polydactylism. Trans. Roy. Soc. Canad. Sec V, 27:169-71. Simpkiss,. M., and Lowe, A. 1961. Congenital abnormalities i n the Afr i c a n new-born. Arch. Dis. Child. 36:404-6. Simoupolis, A. P., Brennan, G. G. Alwann, A., and P i d i s , N. 1967. Polycystic kidneys, i n t e r n a l hydrocephalus, polydactylism i n newborn s i b l i n g s . Pediatrics, 39:931-4. S i n c l a i r , L., ¥interborn, M. H., and Brown, J. 1969. Smith-Lemli-Opitz syndrome. Proc. Roy. Soc. Med. 62:907-8. Sinha, S. 1918. Polydactylism and tooth color. J. Hered. 9:96. Smith, D. ¥. 1964. Autosomal abnormalities. Amer. J. Obstet. Gynec. 90:suppl. -.1055-77. . 1970. Recognizable patterns of Human Malformation: Genetic, Embryo-lo g i c and C l i n i c a l Aspects. Major problems i n c l i n i c a l pediatrics, vol.7. Philadelphia: ¥. B. Saunders Co. Smith, D. ¥., Lemli, L., and Opitz, J. M. 1964. A new recognized syndrome of multiple congenital anomalies. J. Pediat. 64:210-7. Smith, D. ¥., Patau, K., Therman, E., and Inhorn, S. L. 1960. A new autosomal trisomy syndrome: multiple congenital abnormalities caused by an extra autosome. J. Pediat. 57:338-45. Smith, D. ¥., Patau, K., Therman, E., and Inhorn, S. L. 1962. The no. 18 trisomy syndrome. J. Pediat. 60:513-27. 138 Smith, D., Patau,. K., Therman, E., Inhorn, S., and DeMars, R. 1963. The D trisomy syndrome. J. Pediat. 62:326-41. Snodgrass, G., Butler, L. J., Prance, N. E., Crome, L., and Russell, A. 1966. The "D" (13-1'5) trisomy syndrome: an analysis of seven examples. Arch. Dis. Child. 41:250-61. Snyder, L. H. 1929. A recessive factor for polydactylism in man. J. Hered. 20:73-7. .Starke, H., Schimke, R. N., and Dunn, M. 1967. Upper-limb cardiovascular syndrome: a familial study. Amer. J. Cardiol. 19:588-92. Steinberg, J. B,, and Jackson, J. P. 1963. The 16-18 trisomy syndrome. Amer. J. Dis. Child. 105:213-5. Stevenson, A., Johnston, H., Stewart, M., and Golding, D. 1966. Congenital malformations a report of a study of series of consecutive births i n 24 centers. Bull. W.H.O. 34:suppl.:9-127. Stieve, H. 1916. Ueber Hyperphalangie des Daumens. Anat. Anz. 48:565-81. (Cited by Lapidus et a l . , 1943.) Stiggelbout, ¥. 1969. The (Laurence Moon) Bardet Biedl Syndrome. Van Gorcum's medical collection, no. 207. Assen: Royal Van Gorcum Ltd. Streeter, G. L. 1930. Focal deficiencies i n fetal tissues and their relation to intra-uterine amputation. In Carnegie Inst, of Washington, Contrib. to Embryol., no. 126. 22:1-44. . 1942. Developmental horizons i n human embryos; description of age group XI, 13 to 20 somites, and age group XII, 21 to 29 somites. In Carnegie Inst, of Washington, Contrib. to Embryol., no. 197. 30:211-45. . 1945. Developmental horizons i n human embryos; description of age group XIII, embryos about 4 or 5 millimeters long, and age group XIV, period of indentation of the lens vesicle. In Carnegie Inst, of Washing-ton, Contrib. to.Embryol., no. 199. 31:27-63. . 1948. Developmental horizons in human embryos; description' of age groups XV, XVI, XVII and XVIII, being the third issue of a survey of the Carnegie collection. In Carnegie Inst, of Washington, Contrib. to Embryol., no. 211. 32:133-203. . 1949. Developmental horizons i n human embryos (fourth issue); a review of the histogenesis of-cartilage and bone. In Carnegie Inst, of Washington, Contrib. to Embryol., no. 220. 33:149-67. . 1951. Developmental horizons i n human embryos; description of age groups XIX, XX, XXI, XXII and XXIII, being the f i f t h issue of a survey of the Carnegie collection. In Carnegie Inst, of Washington, Contrib. to Embryol., no 230. 34:165-96. Struthers, J. 1863. On variations i n the number of fingers and toes and i n the number of phalanges i n man. Edinburgh New Phil. J., N. S. 18:83-111. (Cited by Lewis, 1909.) "139 Swanson, A . B . , and Brown, K . S. 1962. H e r e d i t a r y t r i p h a l a n g e a l thumb. J . Hered. 53:259-65. Sysak, N. 1928.- About hear ths of P o l y d a c t y l y i n the P o l t a v a Government. Z e i t s . f . E o n s t - l e h r e 12:463-8 . ( C i t e d by Gates , 1946.) Sverdrup , A . 1922. P o s t a x i a l p o l y d a c t y l i s m i n s i x genera t ions of a Norwegian f a m i l y . J . Genet. 12:217-40. Tan, E . L . 1969. P o l y d a c t y l y . J . Singapore P a e d i a t . Soc . 11:147-53. T a y l o r , A . iE. 1968. Autosomal t r i somy syndromes: a d e t a i l e d s tudy of 27 cases of Edward 1 s 'syndrome and 27 cases of P a t a u ' s syndrome. ' J . Med. Genet. 5 :227-41 . T a y l o r , A . I . , and Moores, E . C. 1967. ' A sex chromat in survey of newborn c h i l d r e n i n two London h o s p i t a l s . J . Med. Genet. 4 :258-9 . T a y l o r , A . ID., and P o l a n i , P . E . 1964i- Autosomal t r i somy syndromes, e x c l u d i n g Down's. Guy Hosp. Rep. 113:231-49. T a y l o r , M. B . , Juberg , R. C , Jones, B . , and Johnson, ¥ . A . 1970. Chromosomal v a r i a b i l i t y i n the D. t r i somy syndrome. Three cases and rev iew of the l i t e r a t u r e . Amer. J . D i s . C h i l d . 120:374-81. Temtamy, S. A . 1966a. Ca rpen te r ' s syndrome: a c r o c e p h a l o p o l y s y n d a c t y l y . An autosomal r e c e s s i v e syndrome. J . P e d i a t . 69:111-20. . 1966b. Gene t ic F a c t o r s i n Hand Ma l fo rma t ions . Ph .D . d i s s e r t a t i o n , Johns Hopkins U n i v e r s i t y , B a l t i m o r e . Therman, E . , Pa tau , E . , Smi th , D. ¥ . , and DeMars, R. I . 1961. The D t r i somy syndrome and X® gonadal dysgenesis i n two s i s t e r s . Amer. J . Hum. Genet. 13:193-204. Thomsen, 0. 1927. E i n i g e E i g e n t h u m l i c h k e i t e n der e r b l i c h e n P o l y - und Syndak-t y l i e b e i Mensehen. A c t a Med. ScancL.-65:609-44. ( C i t e d by B e l l , 1953.) Thorburn, M. J . 1970. The pathology and i n c i d e n c e of the D and E t r i s o m i e s i n Jamaica . ¥ . I nd i an Med. J . 19:130-40. Toews, H . A . , and Jones, H . ¥ . , J r . 1968. C y c l o p i a i n a s s o c i a t i o n w i t h D t r i somy and gonadal agenes i s . Amer. J . Obs te t . Gynec. 102:53-6 . Townes, P . L . , and B r o c k s , E . R. [1970] . Imperforate anus and t r i p h a l a n g e a l thumbs: a new autosomal dominant syndrome. In Combined Program and A b s t r a c t s [o f the 80th Annual Meet ing of the Amer. P e d i a t . Soc . and the 40th Annual Meet ing of the Soc . f o r P e d i a t . R e s . ] , A t l a n t i c C i t y , 1970. A b s t r . p . 129. Townes, P . L . , Dehar t , G. E . , J r . , Hecht , F . , and Manning, J . A . 1962a. Trisomy 13-15 i n a male i n f a n t . J . P e d i a t . 60:528-32. Townes, P . L . , Manning, J . A . , and DeHart , G. E . , J r . 1962b. Trisomy 18 (16-18) a s s o c i a t e d w i t h c o n g e n i t a l glaucoma and o p t i c a t rophy . J . P e d i a t . 61 :755-8 . 140 Trowell, H. R., and Hilton, H. B. 1963. Personal communication. Tunte, ¥. 1968. A new polydactyly/imperforate anus/vertebral anomalies syndrome? Lancet 2:1081-2. Turner, B., Dulk, G. M., den, and Watkins, G. 1.964. The 17-18 trisomy and 21 trisomy syndromes i n siblings. J. Pediat. 64:601-4. Turner, H. 1931. Endocrine c l i n i c , diabetes insipidus, Laurence-Biedl syndrome. J. Okla. Med. Ass. 24:148-. (Cited by Temtamy, 1966a.) Uchida, I. A., Bowman, 3i. M., and Wang, H. C. 1962a> The 18-trisomy syndrome. New Eng. J. Med. 266:1198-201.. Uchida, I. A., Lewis, A. J., Bowman, J. M., and Wang, H. C. 1962b. A case of double trisomy: trisomy no. 18 and triplo-X. J. Pediat. 60:498-502. Ul l r i c h , 0. 1951. X. Der Status Bonnevie-Ullrich im Rahmen anderer "Dyscranio-Dysphalangien". Erg. inn Med., Neue Polge 2:456-8. V i t a l Statistics of the Province of Br i t i s h Columbia. 93rd Report for the year 1964. Issued by the Dept. of Health Services and Hospital Insurance. Bri t i s h Columbia: A. Sutton, 1966. Vital. Statistics of the Province of Br i t i s h Columbia. 94th Report for the year 1965. Issued by the Dept. of Health Services and Hospital Insurance. Br i t i s h Columbia: A. Sutton, 1967. Vi t a l Statistics of the Province of Br i t i s h Columbia. 95th Report for the year 1966. Issued by the Dept. of Health Services and Hospital Insurance. Bri t i s h Columbia: A. Sutton, 1968. Vi t a l Statistics of the Province of Brit i s h Colubmia. 96th Report for the year 1967. Issued by the Dept. of Health Services and Hospital Insurance. Bri t i s h Columbia: A. Sutton, 1969. Voight„ ?. Mag. f. das h'eueste der Naturkunde 3:174. (Cited by Parabee, 1903.) Voorhess, M. L., Aspillaga, M. J., and Gardner, L. I. 1964. Trisomy 18 syndrome with absent radius, varus deformity of hand, and rudimentary thumb: report of a case. J. Pediat. 65:130-3. Wagshal-Ives, R., and Berman, J. L. 1963. 17-18-trisomy syndrome. Human Chrom. Newsl. No. 11, pp. 12-6. Walker, J. T. 1961. A pedigree of extra-digit-V Polydactyly i n a Batutsi family. Ann. Hum. Genet. 25:65-8. Walzer, S., Pavara, B., Ming, P.L., and Park, G. S. 1966. A new-translocation syndrome (3/B). New Eng. J. Med. 275:290-8. Warburg, M., and Mikkelsen, M. 1963. A, case of 13-15 trisomy or Bartholin-Patau's syndrome. Acta Ophthal. (Kobenhavh) 41:321-34-Warkany,•J.,.Passarge, E., and Smith, L. B. 1966. Congenital malformations i n autosomal trisomy syndromes. Amer. J. Dis. Child. 112:502-17. 141 Wassel, H. D. 1969. The results of surgery for Polydactyly of the thumb. Clin. Orthop. 64:175-93. Weichsel, M. W., Jr., and Luzzatti, L. 1965. Trisomy 17-18 syndrome with con-genital extrahepatic b i l i a r y atresia and congenital amputation of the l e f t foot. J. Pediat. 67:324-7. Weismann 1893.. The Germ-Plasm. Engl, trans., pp. 428-31. London. (Cited by Lewis, 1909.) Weyers, H. 1953. Hexadactylie, Unterkieferspalt und Oligodontie; ein neuer Symptomen Komplex; Diastosis acrofacialis. Ann. Paediat. (Basel) 181:45-60. W i l l i s , R. A. 1958. The Borderland Between Embryology and Pathology. Pp. 164-9. London: Butterworth and Co. Wilson, G. 1896. Hereditary polydactylism. J. Anat. Physiol. 0. S. 30:437-48. (Cited by Lewis, 1909.) Wilson, M. G. 1968. Rubinstein-Taybi and D, trisomy syndromes. J. Pediat. ' 73:404-8. Wilson, M. G., and Melnyk, J. 1967. Translocation/normal mosaicism in D. trisomy. Pediatrics 40:842-6. Windmiller, J., Marks, J. P., Reimold, E. W., Costales, P., and Peake, C. 1965. Trisomy 18 with b i l i a r y atresia; report of a case. J. Pediat. 67:327-8. Woolf, CM., and Woolf, R. M. 1970. A genetic study of Polydactyly i n Utah. Amer. J. Hum. Genet. 22:75-88. Wright, S. 1926. Effects of age of parents on characteristics of the guinea pig. Amer. Hat. 60:552-9. Yu, F., Gutman, L. T., Huang, S., Fresh, J. W., and Emanuel, I. 1970. Trisomy 13 syndrome in Chinese infants. C l i n i c a l findings and incidence. J. Med. Genet. 7:132-7. Zellweger, H., Beck, K., and Hawtrey, C. E. 1964. Trisomy 18. Report of a case arid discussion of the syndrome. Arch. Intern. Med. (Chicago) 113:598-605. Zirkle, C. 1936. Further notes on pangenesis and the inheritance of acquired characters. Amer. Hat. 70:539. 142 Addenda Blackwell, R. Q., Liu, C.-S., Yang, H.-J., Wang, C.-C, and Huang, J. T.-H. 1968. Hemoglobin variant common to Chinese and Worth American Indians: n 22Glu -» Ala . _ ^2^2 ' S c i e n c e 161:381-2. Cummins, H. 1926. Epidermal-ridge configurations in developmental defects, with particular reference to the ontogenetic factors which condition ridge direction. Amer. J. Anat. 38:89-151. Cummins, H., and Midlo, C. 1961. Fingerprints, Palms; and Soles. New York: Dover Publications, Inc. Kucera, J., Lenz, W., and Maier, W. 1965. Missbildungen der Beine und der Kaudalen Wirbelsaule bei Kindern diabetischer Mutter. Deutsch Med. Wschr. 90:901-5. Mitani, S., 1954. Malformations of the newborn infants. J. Jap. Obstet. Gyneo. Soc. 1:301-15. (Cited by Nishimura, 1970.) Temtamy, S., and McKusick, V. A. 1969. Synopsis of hand malformations with particular emphasis on genetic factors. In Conference pn the Cl i n i c a l Delineation of Birth Defects, 1st, Baltimore, 1968. Birth defects: original article series, ed. D. Bergsma, vol. 5, pt. 3, Limb Malforma-tions, pp. 125-84. New York: The National Foundation. Wood, V. E. 1970. Duplication of the index finger. J. Bone Joint Surg. (Amer.) 52:569-73. , 143 Appendix A Description of Cases Guide to data regarding the probands and key to abbreviations and symbols 1 . The number assigned the family of each proband appears i n the f i r s t column of the l e f t page and the last column of the right page. Probands are grouped according to the affected border of the limb(s): radial duplication, cases 1 - 31; t i b i a l duplication, cases 32 - 37, ulnar duplication, cases 38-91, fibular duplication, case's 92 - 115; ulnar and fibular duplication, cases 116 - 131; and site of duplication unknown, cases 1>32 - 138. 2. A question mark in the third column regarding site of duplication indicates examination of the digits or information from medical records or the family suggested the individual had Polydactyly but this could not be confirmed. 3. The following probands are known to have anomalies in addition to Poly-dactyly. Cases with multiple major anomalies are numbers 4, 6, 14, 22, 38, 43, 46, 66, 68, 70 - 73, 96, 107, 117, 123 - 125, 129 - 131, 133 and 138. Cases with a single major anomaly are numbers 18, 20, 34, 39, 64, 78, 84, 111 and 116. Cases with a minor anomaly(s) are numbers 11 - 13, 15, 42, 83, 87, 91, 102, 118, 120, 121 and 136. 4. The following key refers to the birthplace of the probands: A. Vancouver Island: (a) Victoria, (b) Duncan and Chemainus, (c) Nanaimo, (d) Port Alberni, (e) Tofino and Ahousat, (f) Campbell River B. Greater Vancouver Area: (a) Vancouver, (b) North Vancouver, (c) Burnaby, (d) New Westminster, (e) Surrey C. Praser Valley: (a) Haney, (b) Langley, (c) Mission, (d) Chilliwack D. Powell River 144 E. Kamloops P. Merritt G. Shuswap and Okanagan Lakes Area: (a) Salmon Arm, (b) Vernon, (c) Penticton H. Grand Forks I. Arrow and Kootenay Lakes Area: (a) Nakusp, (b) Castlegar, (c) Nelson, (d) Creston J. Kimberley K. Williams Lake and Alexis Creek L. Prince George M. Burns Lake N. Skeena River. Area: (a) Prince Rupert, (b) Terrace, (c) Kitimat 0. Peace River Area: (a) Fort St. John, (b) Dawson Creek 5. Probands are noted to be of North American Indian (ind) or non-Indian (NInd) parentage. Non-Indian children known to be of Chinese (Chin) or Oriental (Orie) extraction are also noted. 6. Parentheses around a figure for maternal or paternal age indicates con-f l i c t i n g data from different sources or the exact birthdate unknown. 7. Sources of information were interviews with the families by Daryl C. Jones (DCJ), by James R. Miller, Ph.D. (JRM) and R. Brian Lowry, M.D. (RBL), Division of Medical Genetics, U.B.C., and by Public Health Nurses (PHN) as well as various medical records (MRec) including hospital charts, public health records, and personal communication with family physicians. 8. In cases where the pedigree was not taken i n an interview with the fam-i l y , i t has been constructed as f u l l y as possible from the available information. When children i n a. family are known to be half sibs this i s U-5 indicated, however no distinction .is made between legitimate and i l l e g i t -imate progeny. Symbols used i n the pedigrees are the following: 0 / 1 • 1 2 3 male ( i ), female ( i ) and individual of unknown sex (I ) with Polydactyly presence of Polydactyly suspected slanting arrow indicates proband vertical arrow indicates individual has a family history of Polydactyly deceased miscarriage 9. Abbreviations commonly used i n the appendix: A, acces accessory malf malformed, malformation abn abnormal metac metacarpal append appendage me tat metatarsal artic articulation PIP (joint) proximal inter] B bilateral phal phalanx cartilag cartilaginous polyd Polydactyly chrom . chromatin prox proximal dev developed rad radial duplic duplication rud rudimentary excis excised R right ext external synd syndactyly f i b fibular syndr syndrome hypop hypoplastic tib t i b i a l L l e f t U unilateral l a t lateral. uln ulnar MP (joint) metatarsal (-carpal) phalangeal vestig ¥ D vestigial well developed Proband Position D e s c r i p t i o n o f s # d i i t s  number pedigree  1 11^ R radial I I 4 Additional anomalies crib death, age 6 mo. R radial II L radial II R radial shaped like a thumb rather than a skin tag II rather large dolicho-cephalic head; cl e f t l i p and palate; malf. ear R with preauricular append; warty append. L zygoma; flexion contractures of fingers (?); genitalia hypop with defect i n mid-line of scrotum suggest-ive of a c l e f t ; imperfor-ate anus; urachus attach-ed to bladder; sex chrom-atin negative convulsions; failure to thrive; hypospadias; L testicle i n inguinal canal II L radial extra thumb II 11 L radial projects l a t e r a l l y from metac, no bony fusion with shaft of main digit (?) Down's syndrome: floppy body tone; large tongue; fold of skin at nape of neck; CRD (?); wide space between toes 1 and 2 II R radial thumb loosely hanging by skin below main digit 8 R radial na i l present, no bone palpable hemangioma of upper l i p and nose 147 Birth Ethnic Mat. Pat. Source ,,, , _ , , „ _. n. . . . or„ Birthdate Proband Sex Pedigree place origin age age inform. b lb NInd 24 (30) MRec 14 Nov 64 DMV P DCJ H NInd 31 36 MRec 28 May 64 H¥V M DCJ Ob NInd 17 23 MRec 15 May 64 ES . M DCJ Aa NInd 33 38 MRec 17 Jun 66 OTP ' M+ 6 6 6 A.*b* M Ind 18 4— MRec 24 May 67 HIL M Q 5 DCJ • I • , o • • Ca NInd 41 43 MRec 8 Apr 66 MGB M DCJ O T - O Ad^ Ind 17 — MRec 13 Jul 65 MJDC M Q Ba — 19 — MRec 11 Aug 66 GSM M f _ 8 i n , . Description of supern. digits Additional anomalies number pedigree _ _ _ 11^ L radial tied off 10 IV L radial about normal thumb asthma size, lateral at base of main digit , na i l but no bone 11 II L radial skin tag off middle of prox phal, no nail pilonidal dimple 12 II L radial pedicle, na i l but no bone B preauricular appends. 13 II E radial prox phal underdeve- pilonidal sinus loped, and short, distal phal duplic, acces. i s lateral 1.114 R radial distal phal duplic. arrhinencephaly; no sella turcica; multiple defects i n calvafium; assymetri-cal misshapen skull with irreg. defects of cranial bones mainly L; anophthal-mia; at base of absent nose i s a triangular-shaped defect which con-nects with a cl e f t i n upper l i p but also ex-tends through the alveo-la r process of upper gum; mouth small,, micrognathia; gross' malf...pinna B, no external aud. canal B; shield-shaped chest with widely spaced nipples; nonsegmentation of sev-eral cervical vertebrae; hemivertebrae upper dor-sal region; abn. R upper ribs; genitalia small; simian creases B; trigger thumbs B Pedigree L NInd 30 (34) MRec 11 Jan 67 RT M D~[—O DCJ B,d— Nind 17 23 MRec 6 Jul 65 SAH F DCJ 6 6 6 it Ba NInd 39 37 . MRec • 20 Nov 66 MAM F ^ p . Q DCJ " Ba — 21 — MRec 8 Jul 67 RS M Bb — 27 — MRec 30 Sep 65 BJZ M S •• D~f~0 Aa* — 19 — MRec 11 Apr 67 MIP F H •^resided i n Prince George the f i r s t trimester Proband Position ^ ... _ ,. . , m n. Description of supern. digits number pedigree _ _ Additional anomalies 15 II L radial distal phal duplic. malf. pinna R; lowset ears; inguinal hernia B; antimongoloid slant to eyes 2 16 II R radial distal phal duplic, allergy to milk; asthma common prox phal, medial somewhat devi-ated, lateral excised II- abnormal infant, lived 20 minutes; paralysis from chest down 17 II R radial distal phal duplic, common prox phal 18 III L radial prox phal abn wide, duplic distal phal, synd to n a i l , nails separate . strabismus I L radial L: duplic. distal phal, synd. nearly to tip; R: abnormal distal placement of thumb 19 III. L radial metac. and prox phal broad, distal phal duplic, lateral one ¥ D with a nail,' the medial i s deviated but has an IP joint l l " ' ? radial deformed thumb, pro-bably polydactylous, synd. fingers 20 II B radial B prox phal b i f i d , distal phal duplic. c l e f t palate, b i f i d uvula; convulsions at 14" years of age 21 II- R radial acces. append, with two small ossificatn centers, normally developed n a i l , at-tached near head of metac, no articulatn 151 Birth Ethnic Mat. Pat. Source , „ , . _ , . . or_ Birthdate Proband Sex •place origin age age inform. . Bb Wind 27 30 MRec 9 Nov 65 GTW M DCJ Bd Wind 17 21 MRec 28 Jan 64 CAL M DCJ Pedigree 5 ? 15 O-r-O-T—• 16 Oa 26 MRec 22. Mar 65 DRP M Ab Wind 25 - 30 MRec DCJ 30 Aug 66 LFB P a-r-o 17 18 Ab 22 MRec 21 Feb 65 JPB M "b-r-o 19 Ba 27 Ba Wind 35 37 MRec 1 Dec 64 JJDM M D-MRec 22 Jan 64 DCJ CEC F O - i - O 20 21 Proband Position number pedigree Description of supern. digits 22 II ' R radial ¥ D, two ossified phals, nai l and •' dermal ridges, at-tached near head of metac, no articulatn 23 II R radial acces. i s lateral & somewhat hypop, two phals, the base of prox phal attached to epiphysis of the medial prox phal 3 24 II R radial common metac, l a t . & medial thumbs of approx equal size, biphal, synd at prox phal, overlapping at distal phal Additional anomalies high arched palate; malf. pinna and ext. auditory canal L; webbed neck; CRD: VSD, pulmonary valve atresia with hypop. R ventricle, PDA, pro-fusing pulmonary arteries which are hypop, L aortic arch, L descending aorta, R superior vena cava, R inferior vena cava; ribs notched R; multiple hemi-vertebrae upper thoracic region R; b i f i d verteb. lower thoracic region; allergies B vesicoureteral reflux II- B synd fingers 4-5 25 II R radial acces. rud. cartilag metac and two phals, medially located, partial synd of two thumbs 26 II-II L radial acces. ¥ D, prox phal attached to b i f i d metacarpal feet abnormality, braces u n t i l age 11 II microcephalic; meningo-cele; died age 3T days 27 II R radial acces lateral with somewhat hypop metac & one phal, joint at lower third 153 Birth Ethnic Mat. Pat. Source place origin age age inform. Be, Wind 25 34 Birthdate Proband Sex Pedigree MRec 15 Aug 64 DCJ GIM M+ • - o-T-a 22 Bd Wind 29 36 MRec 20 Sep 66 KAW P DCJ D-T-O 23 5 T i Ba Wind 33 33 MRec 2 Aug 64 RMD DCJ M D-24 Ba Wind 28 28 MRec 16 Dec 67 PJS . P DCJ O-r—O 25 Ga Chin 28 38 MRec 25 May 66 HMSW M DCJ O-j-O 26 6 66 c V i i ti L Wind 22 25 MRec 21 Jul. 67 GRB M DCJ D -T -O 27 c5~6S~b Proband Po s i t i o n i n number pedigree Description of supern. d i g i t s Additional anomalies 28 I I R r a d i a l acces l a t e r a l & more proximal & smaller, rud. metac & 1 phal; d i s t a l j o i n t main thumb adducted medi-a l l y , slight- deform-i t y of the phals 29 IT R r a d i a l (L t r i p h a l ) R: 2 t r i p h a l thumbs, synd to PIP j o i n t , fusion of two prox phals, l a t e r a l excis. L: t r i p h a l thumb . 30 I I R r a d i a l rud. metac l a t e r a l & attached to normal metac,. acces has 3 phals, the prox & medial at 90°; medial thumb i s biphal & deviated medially 4 31 I I • L r a d i a l acces ¥ D t r i p h a l thumb, l a t e r a l , with n a i l , a r t i c u l a t i o n to reduplic head of metac 32 I I R. t i b i a l 33 34 I I I T 3 B t i b i a l B: p a r t i a l duplic, synd. to n a i l , L better developed B t i b i a l double bones i n t i p of b i g toes pinpoint cataract R cataracts I I reduction deformity of a l l four limbs cataracts 35 I I R t i b i a l metat short & thick, prox & d i s t a l phals duplic, toe pointed medially 90° I I 1 s t i l l b o r n , 28 weeks ges-ta t i o n 155 Birth Ethnic Mat. Pat. Source _.. , , _ •, , „ , . . . or _ Birthdate Proband Sex place origin age age inform. ; Ba Ba 27 MRec 25 Apr 67 PM Ba Wind 26 30 MRec 7 Oct 64 DCJ Pedigree 29 — MRec 15 May 65 KBS M SJB P IMQ M ? • n — O D-28 29 30 Ba — 32 (34) MRec 24 May 66 RPT M Be Ba 28 — MRec 31 Aug 67 SJER M 17 MRec 25 Apr 65 LDB P 0a Wind 26 29 MRec 9 Mar 67 LMB F DCJ K Wind 19 30 MRec 4 Sep 66 WC DCJ M D-T-O •- - O ' o / r O 31 32 33 • 34 • C h - r - O Proband Position number pedigree Description of supern. digits Additional anomalies 36 I I B t i b i a l B: common metat with two articular faces, lateral ray better developed, synd. to tip, separate nails 37 38 39 40 41 i r I I i i -I I I I I 5 l i -re i i -B t i b i a l R ulnar R ulnar R ulnar B ulnar R better developed; two distinct mobile toes, common metat, biphal, c l e f t to PIP joint; L synd. to tip, separate nails, common metat, phals separate acces 5th digit pedicle off deformed 5th finger, synd of 3 - 4 fingers R acces tied off acces with nai l & bony tissue IT ulnar skin tag B ulnar ¥ D acces fingers R ulnar pedicle off 5th at level of PIP joint Smith-Lemli-Opitz Syndr. R f a c i a l palsy; high arched palate, no true c l e f t ; small, (?)lowset ears; micrognathia; asymmetry of jaw & neck folds; CRD: aortic steno-sis & PDA; anomalous ext. genitalia: hypospadias, cryptorchidism, patent urachus; B clubfeet with toe deformities; L hand: wide c l e f t between.2 - 3 fingers; sex chrom. neg. small hematoma; congen-i t a l f i s t u l a of the tear*sa!c of L eye 42 I I ' R ulnar acces at base of 5th R hydrocoele of tunica vaginalis; birth mark just above umbilicus 157 Birth Ethnic Mat. Pat. Source n , . n „ , . . . or„ Birthdate Proband Sex place origin age age inform. Be Mind 19 21 MRec 1 Mar 64 RLS M DCJ Pedigree o—r-o 36 (Aa) MRec 1 Jun '65 JEW M O - r O Stik V 31 Aa Nlnd 34 47. MRec 24 Jul 67 JEB M RBL ' DCJ O-r-O 38 Be 32 30 Ba Nlnd 18 26 MRec 27 Feb 66 DCJ MRec 20 Dec 66 DCJ GWJ M On—O—|—• 39 ARM M 7-O-r-O 40 Ba Nlnd 30 31 MRec DCJ 7 Dec .6.7 DEP M •nr-O Ba 25 MRec 7 Dec 66 AJN M 6 6 i 6 / 41 42 Proband Posxtxon ^ ... . „ ,. ., m n. Description of supern. digits number pedigree _ 43 II L ulnar acces digit Additional anomalies Trisomy D syndrome: tower head, c i r c . of 11"; slanting eyelids; atro-phic nose; B c l e f t l i p & palate; lowset, abn. ears; •flaccid neck; underdeve-loped penis and scrotum; cryptorchidism; (?) D/D translocation I I ' B ulnar pedicles 44 I I L ulnar deformed acces f i n -ger off 5th Trisomy D syndrome: infantile spasms; M R; upturned nose; long upper l i p ; centerline of soft palate prominent; mildly dysplastic ears; small um-b i l i c a l hernia; B crypt-orchidism; simian crease R; D/D translocation D/D translocation 45 I I L ulnar rud. acces. digit lateral to 5th with nail and cartilage 5 46 I I I L ulnar acces predominantly soft tissue Trisomy D syndrome: B c l e f t l i p & palate; large beak-like nose; malf. ear; CHD: probably VSD; kidney anomaly (?); small abn. penis partly fused to scrotum; crypt-orchidism; calcaneal varus clubfoot R; M R ; trisomy of chrom. 17-18 47 II B fibular L ulnar acces 5th tied off 48 I I L ulnar skin tag 159 Birth Ethnic Mat. Pat. Source , , _ , no . . or„ Birthdate Proband Sex place origin age age inform. Pedigree Be NInd 26 28 MRec 10 Sep 67 R M DCJ D-r-O 43 Bd Ac 22 25 MRec 2 Mar 66 KDB P MRec 11 Jul 66 BAB M Af NInd 35 39 MRec RBL 16 Nov 66 B M' D-r-O 45 6 66 * D-O - r O 6 6 A 6 i * E 19 MRec 24 Feb 66 RM M 28 — MRec 24 Feb 64 MDT F Q - T - < ) 47 Q - p O 48 Proband Position ~ ... „ ,. . , m,. Description of supern. digits number pedigree  49' II L ulnar skin tag Additional anomalies coarse skin II- D & C revealed tissue of a fetus, development had ceased early i n gestation II hydrocephaly; CHD 50 II' L ulnar skin tag 51 II L ulnar pedicle off 5th at l e v e l of prox phal 52 II L ulnar pedicle off 5th at l e v e l of prox phal tongue-tie; prepuce re-tracted 55 II II 14 L ulnar pedicle off 5th at l e v e l of medial phal ptosis L 54 II L ulnar pedicle hematoma on head 55 III L ulnar pedicle 1 II B ulnar acces d i g i t s normal length of 5th but perpendicular to 5th d i g i t s , did not bend 2 56 II L ulnar pedicle without a hernia n a i l & probably no bony tissue 2 I L ulnar wartlike pedicle 57 11^ L ulnar acces 5th connected by a long pedicle, t i e d off 5 58 II • L ulnar skin tag l a t e r a l off 5th' at l e v e l of prox phal, no bone or cart. B lopped ears 161 Birth Ethnic Mat. Pat. Source ,, , , _ , , „ . . or_ Birthdate Proband Sex place origin age age inform. • Pedigree Gh Wind 20 28 MRec 19 Apr 64 DRMK M . D " DCJ • o 49 6 4^6 6 6 Ba Gc 25 20 MRec 18 Aug 67 L M MRec 22 Sep 66 S M Q- •O l a Wind L Ind Ba Bd Wind 17 20 MRec 14 Jul 65 BAR M DCJ 37 46 MRec 22 Jul 65 BAC P DCJ D 4 - O 50 51 52 53 24 D-T-O / 5 4 MRec 2 0 J u n 66 CPC M 21 22 MRec 30 Apr 67 RBA M DCJ TL 55 Bd Wind 24 (27) MRec 21 Sep 65 WDJ M Q — , — H L ] 6 / 56 DCJ Cd — 29 MRec 21 Sep 66 H P Ba Wind 28 27 MRec 4 Nov 66 RQL M DCJ O-rO D - r - O 57 58 • 6 6 6 i Proband Position _ ... „ ,. . , xn,. Descrxptxon or supern. dxgxts number pedigree  Additional anomalies 59 60 II II II' 1 L ulnar acces phal off 5th at level of medial phal, attached by skin L ulnar pedicle with c a r t i l . center off prox phal of 5*, no nai l cancer 61 H i -l l L ulnar U ulnar pedicle with vestig. n a i l , no bony tissue 62 63 64 65 66 II II II-II-II II' L ulnar L ulnar L.ulnar L ulnar B ulnar pedicle with c a r t i l . tissue attached to medial phal of 5th pedicle with c a r t i l . tissue pedicle with bone & a fingernail pneumonia, age 6 weeks operation for squint abnormal heart valve ¥ D acces digit, tongue-tie articulates l a t e r a l l y with head of 5th metac Smith-Lemli-Opitz syndr.: intrauterine growth re-tardation; postnatal failure to thrive; micro-cephaly; hemangiomas on upper eyelids & forehead; glossoptosis; broad nose and upturned nares; c l e f t palate; broad maxillary alveolus; slanted ears; micrognathia; CHD: ASD & VSD; aplasia of kidneys; deep sacral dimple; cut-aneous pi t anterior to anus; synd toes 2-3; 8/ 10 whorls; Hirschsprungs Disease 163 Birth Ethnic Mat. Pat. Source , , _ , , „ . . • of„ Birthdate Proband Sex place origin age age inform. •• • •  Aa — 33 — MRec 23' May 65 AM P Pedigree 19 D-r-O Be Nlnd 37 40 MRec 20 Feb 65 DMS P DCJ O 59 60 / Bb Hind 36 36 MRec 2 May 66 SJK P DCJ Q-7> E • Kind 30 29 MRec 14 Nov 66 JLH P DCJ Aa Nlnd 22 22 MRec 14 Jan 66 SC M DCJ Ob Nlnd 27 32 MRec 21 May 66 KAH P DCJ ffTrO 6 ill i 1 4 D-r-O o C H j O D f MRec 16 Oct 66 DSL M E Hind 31 34 MRec 24 Dec 65 SJR* P JRM DCJ I D - r - O • 61' 62 63 64 65 66 ^originally described by Lowry et a l . , 1968. Description of stipe rn-. digits Additional anomalies B ulnar f a i r l y ¥ D acces, no articulation L ulnar pedicle tongue-tie; abnormal feet B ulnar pedicles, no bony tissue B ulnar acces at base of 5th large fontanelle; microph-thalmia; B'cleft l i p & palate; small, (?) lowset ears; C H D : PDA & foramen ovale, hypertrophy R ven-t r i c l e , large septal defect; kidney abnormal.; cryptorchidism B ulnar acces digit L ; rud. acces digit R B ulnar B ulnar B ulnar B: arising from prox Trisomy D syndrome: phal; L better dev. microcephaly; absence of with whorl on finger- frontal areas of brain; tip; R consists of a peculiar pigmentation on pedicle forehead & upper eyelids; anophthalmia; broad nose; hypop helix L ear; c l e f t palate; C H D ; absence of R 12th rib; umbilical her-. nia; clenching of hands; D/D translocation pedicles pedicles antimongoloid slant; heart murmur; floating, kidney; B hernia; synd. complete B c l e f t l i p ; c l e f t palate, absence of median maxillary process; hypogenitalism: penis ex-ceedingly small with l i t t l e erectile tissue, scrotal sac extremely . small; cryptorchidism; agenesis, of pituitary; hypoplasia of adrenals; thymic tissue i n thyroid; no c l i n i c a l CHD 165 Birth Ethnic Mat. Pat. Source , , „ , , „ . . or„ Birthdate Proband Sex place origin age age inform. Pedigree D Nlnd 22 23 ' MRec 17 Jul 6"5 MAGK M Q-j—O DCJ Bh Nlnd 31 44 MRec DCJ 2 Jul 67 BJG M O r O • 67 68 E Nlnd 22 27 MRec 11 Dec" 67 SPR M DCJ Bd Nlnd 24 24 ' MRec 16 Jun 66 LDP P' JRM • . D-r-O D- -O 69 70 Ba Nlnd 28 31 MRec 17 Feb 65 WEN M DCJ Aa 22 MRec 14 Feb 65 MWH M D-i-O 5 T ^ 71 72 Proband Position number pedigree 73 I I 1 Description of supern. digits B ulnar pedicles at base of 5th, tied off Additional anomalies hypotonia, quadriplegia; cerebral hypoplasia; hydrocephalus; M R; flame naevus over forehead; de-pressed bridge to nose; somewhat small eyes; low-set ears; partial c l e f t palate and uvula; enamel hypop. of teeth; hearing handicapped; electrolyte imbalance; CHD; poly-cystic kidneys'; developed anemia I I L fibular p a r t i a l l y synd acces 5th toe, with nai l large head, c i r c . 38 cm; hydrocephalus; patent fontanelles B; prominent forehead; deeply set eyes; epicanthic folds B; de-pressed nasal bridge; lowset abnormal ears; V-shaped notch i n posterior edge of hard palate; large thymus; large poly-cystic kidneys B; small acces spleen; chromosomes: normal XX complement; lived 2rz hours 74 I I I -i r I I 8 B ulnar B ulnar B ulnar pedicles 75 I I - 'B ulnar pedicles 76 I I B ulnar L: pedicle off prox phal. of 5th, no bone; R: tiny nubbin of tissue off prox phal of 5th bowel obstruction due to hydrocoele of testis R I I s t i l l b o r n , died about 4i* 5th month of gestation 77 I I B ulnar skin tag off 5th indirect inguinal hernia R Birth Ethnic Mat. Pat. Source _.. no T, • , . . or„ Birthdate Proband Sex Pedigree place origin age age inform. ° Ba Nlnd 19 30 MRec 12 Nov 66 DGA P + O—r~0 13 Ba Nlnd** 34. 33 MRec 20. Aug 66 DCJ WDPB M 6 6>*h <£> 4 D-r-O 74 Cc — 21 E Nlnd 35 33 MRec 20 Mar 67 RJP M MRec 26 Dec 64 DCJ 6 6666*664 D-r-O ^ 6 + i 6 • GPT M 75 76 Cd Nlnd 22 (22) MRec 25 Jul 64.' MAP .M **one grandparent of French-Indian descent D-r-O Proband Position i n number pedigree 78 I V IV Description of supern. digits B ulnar B ulnar B t i b i a l pedicles with, nail Additional anomalies L: synd. toes 2 - 3 the complete length; R: synd. toes. 1-2-3 complete length; died of pneumonia acces fingers f a i r l y R: synd. fingers 3-4—5 ¥ D with nails; very broad thumb L; L: acces toe with duplic. metat fused to normal 1st metat; R: rud. nubbin l a t -eral to main toe complete length with bony union d i s t a l l y of 3-4; L: synd fingers 3—4 the complete length; feet: synd. toes 1-2-3 B i n * radial 79 III' III II 8 II* 80 II* II II II* II' II B ulnar L t i b i a l TJ radial ? ulnar L radial ? ulnar B ulnar wide thumb with i n -dented n a i l ; deformed 5th finger unilateral synd. toes 2 - 3 B pedicles; duplic. distal phal' with bone, no a r t i c . f l a t wide thumb with indentation i n n a i l ; deformed 5th finger B, wide di s t a l l y f l a t wide thumb with slight indentation i n n a i l ; L: partial synd fingers 4 - 5 with camptodactyly. of 5th; R: partial synd 4-5, 5th i s wide d i s t a l l y pedicles heart attack B ulnar pedicles premature, approx 6 mo, gestation premature, approx 7 mo. gestation high palate; lordosis inguinal hernia eczema 169 Birth Ethnic Mat. Pat. Source _,. , , , , „ . . of_ Birthdate Proband Sex place origin age age inform. Ab Nlnd 20 22 MRec 27 Aug 64 CLN Pedigree O - r - O 78 • • • i • Nlnd 27 36 MRec 11 Aug 64 DCJ JDP M D - r - O 79 •+D+6 6 • 6 Bd Nlnd• 36 39 MRec 21 May 66 DCJ JtfP M 80 81 II B ulnar pedicles Additional anomalies hemangioma on head 82 83 II II-II B ulnar pedicles off 5th at level of PIP joint, (?)medial aspect, suggestion of nails B ulnar skin tags systolic murmur still b o r n hemangioma of scrotum 84 II B ulnar skin tags on lateral hypoglycemia aspect of 5th 85 III B ulnar skin tags at base of 5th, lateral aspect 5 III L t i b i a l partial duplic. of toe, synd. nearly to tip 7 86 « III B ulnar acces digit with bone and nai l but no a r t i -c u l a t i o n , tied off 2 III R ulnar small wartlike acces digit 3 III L ulnar acces digit with bone and nai l but no a r t i -culation III B ulnar B fibular acces digits f a i r l y ¥ D with bone and nai l i r B synd toes 2 — 3 about half the length II II 8 L radial broad thumb B synd toes 2 - 3 about a quarter of length L radial broad thumb 171 Birth Ethnic Mat* Pat. Source _. ,, , , _. . . „-.• . . • " or„ Birthdate Prohand Sex place origin age age' inform. Pedigree L Kind 31 31 MRec 1 Aug 64 C AH F Q—|—O DCJ Ba NInd 35 MRec 13 Jul 65 SJP P L NInd 21 27 MRec 23 Aug 67 RWM M DCJ D - j O - H D h - T - n / D - r O Ba 21 Aa NInd 30 31 MRec 12 Jan 67 JDW M -o L NInd 39 .. 49 MRec 16 Aug 64 LAW M DCJ 81 82 03 MRec 4 Bet 65 LL M j Q 84 i /rs+ 85 86 0 Proband Position „ j - •+ • i n , . Description of supern. d i g i t s number pedigree _ _ Additional anomalies 87 A B ulnar rud. acces d i g i t at- hematoma L upper arm tached to (?)medial aspect 5th finger o f f proximal phal B ulnar "one j o i n t " attached to l a t e r a l base of 5th by thread of skin . I V Down's syndrome 88 89 I I I I I I I I I R r a d i a l r a d i a l B ulnar B ulnar webbed toes L: large pedicle; R: wart-like pedicle; both with bony tissue L: pedicle with bony feet s l i g h t l y pronated and cartilaginous tissue; R: skin tag 90 I I I B ulnar pedicles with bony d i s t a l phal and n a i l 1^  B ulnar 91 I I B ulnar 5th metac broad and b i f i d a r t i c u l a t i n g with 5th and acces. ears abnormal 92 I I R f i b u l a r ¥ D acces folds over top of foot, p a r t i a l syndactyly with 5th epilepsy since age 5 or 6 93 I I ' •B f i b u l a r complete ¥ D acces 5th toes I I R ulnar wart-like pedicle on l a t e r a l aspect at base of 5th hernia 94 L f i b u l a r probably f a i r l y ¥ D pneumonia 173 Birth Ethnic Mat. Pat. Source T5. ,, , , ^ o . . or „ Birthdate Proband Sex place origin age age in f o r m . _ _ _ _ _ _ Pedigree lb NInd 25 30 MRec 18 Oct 66 TAT M O DCJ -o - o 87 D •6 rj _ 6+6 • _7rr_ Ba — 24 Gc 17 MRec 7 Peb 67 SLB P MRec 7 Nov 64 ILS P Ca NInd 20 MRec 28 Jun 66 DCJ JIS M Ba NInd 30 29 Ba NInd 38 37 MRec 21 Nov 66 DCJ MRec 23 May 66 DCJ AMG M MGAS M D - T -O D- - o - T - a i 4 D-o / D-6 6 6 * 6 Ca NInd 26 33 MRec 25 Jun 66 DCJ DWC M -o • & - a 6 88 89 90 91 92 93 Ae Ind MRec 1 Sep 64 JPS M O 94 Proband Position number pedigree Description of supern. digits Additional anomalies 95 II B fibular L: skin tag R: acces & 5th a r t i -culate with broad me tat,' both move actively 96 I F R fibular tied off narrow, high arched palate; very lowset ears; systolic murmur along LSB; spina bifida; abdom-inal musculature & sub-cutaneous tissue somewhat atrophic or hypop, rectal prolapse 97 i r R fibular pedicle 98 II L fibular cartilag. mass to lateral side of main digit, appeared as enlarged l i t t l e toe 4 99 III B fibular double toe nails on 5th, acces lateral 4 II B fibular double toe nails on 5th functional heart murmur 100 II L fibular broad 5th toe, inden-tation & division into two nails heart defect; abnormality of lungs; colostomy un t i l age 2; hernia 101 II R fibular broad 5th toe, redupl. of phals with some abnormality of me tat, lateral excised 102 II B fibular L: small acces phals medial, synd almost . complete length A-5> two nails; R: small acces phals l a t e r a l , synd 4-5-A to n a i l , 5th & acces share nai l L ear tag; tongue-tie 175 Birth Ethnic Mat. Pat. Source , . , 0 . . or„ Birthdate Proband Sex place origin age age inform. Ba — 20 — MRec 8 Feb 66 FKF M Pedigree Ic Nlnd 34 34 MRec 25 Sep 64 RZS F DCJ Q - r - O 95 * 6 6 • 4/ D-r-O 96 5 T o ~ i (Ba) Nlnd 24 28 MRec 6 Jun 67 JRD M DCJ Ba Nlnd 25 26 MRec 7 Nov 66 DJE DCJ Ba Chin 24 26 MRec 29 Jul 64 ¥KL DCJ • M M Oa Ind 25 32 MRec 6 Feb 65 DGM '*• DCJ M D - r - O 97 98 99 6 6 6 i - p o D -O • 6 • • 6 m Be Nlnd 32 32 MRec 19 May 66 MAP F DCJ Ac Nlnd 19 22 MRec 12 Sep 67 ALF M DCJ D •O 101 D 6 D 4 D D- -o 102 Proband Position ^ ... „ ,. . , m,. Description of supern. digits number pedigree _ _ Additional anomalies 103 II R fibular acces medial to 5th, 5th and acces. share n a i l , synd 4-A-5 104 II R fibular acces quite complete with three phalanges 1 I L fibular enlarged 5th toe with two nails 105 I V L fibular two toes arising from 5th metat, each with two phalanges III L fibular skin tag off 5th 106 II 107 II 8 L fibular acces small, l a t e r a l prox & distal phals calcified,, well formed toe but did • not bend B fibular L: very broad 5th metat with two a r t i -cular surfaces on i t s head; R: five metatarsals Pierre Robin anomaly: glossoptosis; high soft palate; hard palate; mid-line longitudinal ridge represents an incipient c l e f t palate with vomer visib l e ; micrognathia II drowned II" died when i l l with high fever II II' lived one day lived six days 108 II L fibular five metats, acces . articulated with MP joint, nail present 109 II L fibular acces toe inserted between the 4th & 5th, bony spur seemed to articulate with 5th metatarsal 177 Birth Ethnic Mat. Pat. Source -n , , 0 . . or„ Birthdate Proband Sex place origin age age inform.  Pedigree Ba 17 MRec • 3 Mar 66 KAK P o 103 Bd — . 31 — MRec 16 Mar 65 RMC P PHN 104 Gb Ind 19 22 MRec 17 Peb 65 PDGM M DCJ T 105 Ba NInd 29 34 MRec 29 Apr 66 GMC M y A DCJ / • — r O 106 cTiTl) Nc NInd . 37 41 MRec 22 Jun 67 NMV M DCJ • — r - O 107 • D + D + 6 6 6+ _6 Be Orie 29 — MRec 3 Nov 67 DAY M Chr^ O 108 E — 33 -- MRec 19 Jan 64 CMY M / 109 Proband Position ^ ... „ 1. . , in , . Description of supern. digits number -pedigree _ Additional anomalies 110 V .15 B fibular (2 acces L) L: rud. acces 4th metat with phals i n -serted between toes 3 & 4 ; addtnl c a r t i l spur .• off head of 5th metat with associatd soft tissue, synd of 4-5-A (?); R: c a r t i l . spur at Jiead of 5th metat & assoctd tissue VI B ulnar B: rud. acces metac. inserted between 4th & 5th metac, prox phals of acces & 5th fused by cartilag. epiphysis, synd A-5 to middle phalanx; B fibular B:common 5th metat, 5th & acces prox phals side by side, no os-si f i c a t i o n centers for acces middle or distal phals; L: synd 5 - A V B ulnar B fibular B ulnar B fibular B ulnar U fibular V 10 V •14 B ulnar B fibular B t i b i a l R ulnar B fibular B ulnar (2 acces B) B fibular* B f i b : acces i n -serted between 4 * & 5th .uln: wide 5th finger & n a i l ; f i b : lateral L: metacs 3 - 4 fused at base, rud acces metac medial to normal 5th, partial synd A -5 j addtnl acces lateral to 5th: skin tag with cartilage; R: rud 6th & 7th metacs, synd 5 - 6 complete length, 7th has two phals; B f i b : six metats 179 Birth Ethnic Mat. Pat. Source ^. ,, , , -n , , 0 . . or„ Birthdate Proband Sex place origin age age inform. Bb -Nlnd 30 36 MRec DCJ 8 Oct 65 RHA M i Pedigree i i JhrO i-rO 6 • Proband Position number pedigree 110 r r Description of supern. digits Additional anomalies B ulnar B fibular '¥ D digits on the hands and feet IV B ulnar uln: nubbins B fibular f i b : ¥ D digits IV^ B ulnar uln: nubbins, synd 4 - 5 the entire length B fibular f i b : ¥ D digits Q IV B ulnar uln: nubbin L; R has acces medial to 5 t h ; B fibular f i b : acces numeri-cally the 4 t h toe q IT B ulnar nubbins on the ? fibular. hands and feet 2-III- B ulnar uln: nubbins, synd R B fibular f i b : ¥ D digits, synd 4 III B ulnar ¥ D digits on the B fibular hands and feet II' U ulnar ? fibular nubbin 111 112 1 1 3 II II' II polyd L fibular B fibular R fibular acces toe inserted between the 4 t h & 5 t h , acces metat project-ing from 4 t h with somewhat hypop prox & distal phals, synd A - 5 to prox phal B: acces medial to 5 t h , 5 t h & acces both articulate with 5 t h metat; R: no proper n a i l ; L: nail present acces toe medial to 5 t h , metat present cataract R eye asthma; eczema 5 1 1 4 II L fibular rud. acces metat i n -serted between 4 t h & 5 t h , abn, bone attached to normal 4 t h and 5 t h metats by cartilage, ¥ D toe with 3 phals 181 Birth Ethnic Mat. Pat. Source T, , , „ n . . or. Birthdate Proband Sex place origin age age inform. Pedigree 18 — MRec 15 Oct 67 LDH P ' Q—i—Q 111 Be 31 — MRec 11 Dec 65 • JAD M Ba NInd 26 27 MRec 11 Dec 67 LGM DCJ Ic wind 32 36 MRec 27 Jun 64 DLM DCJ r-X -o / D-i-O 6 6'A) 1 112 113 114 Description of supern. digits Additional anomalies R fibular partial synd of 4th and acces B ulnar acces digits at base B fibular of 5th pilonidal sinus; enlarged l i v e r B ulnar L fibular R ulnar R fibular B ulnar R fibular finger-shaped and attached at 5th metac, no articula-tion (?); toe-shaped, no ar t i -culation (?),synd. toes 2-3 and 5-A L, 2-3 R small bony spike on under side of 5th rud. acces. toe at-tached by twisted pedicle, with nail pedicles with n a i l ; pedicle, no nail CHD; sternal anomaly Smith-Lemli-Opitz rsyndr.: elongated head, sugges-tive of microcephaly; ptosis; broad maxillary alveolus; high arched palate, no c l e f t ; micro-gnathia; large pinnae, somewhat low and slope backwards; short neck; pigeon chested; anoma-lous ext. genitalia; complete ventral hypo-spadias with b i f i d scro-tum; cryptorchidism; hips do not abduct f u l l y ; feet tend to be i n c a l -caneovalgus position; XY chromosome complement birth mark on labia major IJ fibular acces digits L ulnar B fibular pedicles B supern. nipples below normal ones B. ulnar R: ¥ D acces with phals & nai l , tied off; L: better developed, excised cerebral palsy; R hemi-plegia; speech problem 183 Birth Ethnic Mat. Pat. Source , , _, , , _ . . .  of _ Birthdate Proband Sex place origin age age inform. . E Ind 19 — MRec 19 Mar 65 AGS P Pedigree P Nlnd 42 42 MRec 6 Mar 64 AD P DCJ + Q- -O 115 116 Af Nlnd 18 22 MRec 3 Nov 67 TMK M RBL 6 6 6 6 6 + 6 6 •* Q — r O 117 Id Nlnd 25 25 MRec 1 Sep 65 WLS P DCJ D - -O 118 6 6 * • Na Ind 20 21 MRec 31 May 66 KAS P DCJ Ba Nlnd 17 19 MRec 14 May 67 KBJ M RBL DCJ 119 120 •6-r-a 6 6 i d 6 • • Description of supern. digits Additional anomalies B ulnar B fibular B ulnar B ulnar B ulnar B fibular R ulnar L ulnar B ulnar (2 acces R) R fibular B ulnar B fibular B ulnar B fibular acces fingers with two birth marks three phalanges, no acces metacarpal, no articulation; L: single phal pre-cursor; R: acces with two rud. phals acces off prox phal L: pedicle; R: acces with osseous or cartilaginous con-nection; L: head of 5th metat broad, acces medial to 5th, acces & 5th articulate; R: hypop acces toe, no a r t i c . pedicle pedicle 7 L: acces digit R: acces digit l a t . to 5th with 2 or 3 phals, no metac; plus 2nd acces digit inserted between 5 & 4 with 3 phals and rud. metacarpal; acces digit finger-shaped digits with bone, no artic, B: acces toe with 1 phal, articulates to lateral aspect head of 5th metatarsal finger-shaped digits without bone; acces toes with bones antimongoloid slant to eyes muscle tone poor; hyper-telorism; micrognathia; high arched palate; CHD: VSD, R ventricular hyper-tension, markedly dextro-posed aortic root, com-plete pulmonary artery atresia with a hypop. main pulmonary artery, PDA; synd. toes 2-3 B Polydactyly/imperforate anus/vertebral anomalies syndrome: imperforate anus with rectoperineal f i s t u l a ; abn's R upper thoracic cage; megacolon megacolon chronic constipation problems; synd. toes 2 - 3 : R 2 /3 the length, L 1/3 the length 185 Birth Ethnic Mat. Pat. Source ~. ,, , , - , , „ ' ^. or„_ Birthdate Proband Sex Pedigree place origin age age inform. Ob Nlnd 23 — MRec U Jul 64 MJS P DCJ 1 121 2>* 6| • ^66+^6*6+6 E Nlnd 34 30' MRec 29 Oct 66 SB DCJ o- 122 Ca Nlnd 22 24 MRec 23 Jan 64 DLN P' DCJ O-r-O 123 6 6 *+ * Ad Nlnd 26 27 MRec 21 Sep 67 CCC DCJ M O o 124 •o 6~i~b Proband Position _ ... „ ,. ., m n. Description or supern. digits number pedigree _ 125 I V •B ulnar B fibular nonfunctional finger-shaped .digits barely attached; whorls on fingertips of acces; acces appeared ¥ D, inserted between 4th and 5th Additional anomalies Giant c e l l hepatitis: low lying ASD with mitral and tricuspid i n s u f f i -ciency due to hypop. of septal cusps; congenital atresia of bile ducts (common bile duct); pilonidal dimple IV ? polyd arthrogryposis multiplex congenita; CDH; abn. of testicles and scrotum IV Giant c e l l hepatitis: cirrhosis of l i v e r and li v e r failure; cong. atresia of the common bile duct IV III 8 B fibular acces 5th toes B ulnar B fibular Giant c e l l hepatitis: ASD; lowset ears; mal-formed gums CHD: cong. spondylo-listhioses; primary lower incisors never erupted; perforation of R eardrum 126 II' B ulnar B fibular acces digits ¥ D with three phals, no sixth metac or metat, minimal synd of 5th and 6th digits II virus pneumonia 127 IV B ulnar B fibular B acces digits a r t i -culated with 6th metac or metat, L 6th finger less ¥ D III nr II B ulnar B fibular L fibular fibular pedicles, tied off; B: ¥ D acces, artic. with 6th metatarsal articulated (?) I polyd 187 B i r t h Ethnic Mat. Pat. Source T). ,,, , „ , , of„ Birthdate Proband Sex place o r i g i n age age inform. Pedigree Ba Wind 24 28 MRec 16 Aug 67 BTAS M Q-RBL -o 125 6+6 ti o ti 6 6=|6lj] O 6 *+* Ch NInd 26 32 MRec 13 May 66 GFT DCJ M Q" O 126 i d NInd 23 23 MRec 23 Mar 65 MGK DCJ M I 127 -o o-i l l cv7> Description df supern. digits Additional anomalies R ulnar B fibular small finger-shaped digit with 3 phals, articulates with head of 5th metac.5. ¥ D acces later a l , articulates with b i f i d 5th metat L, . broad head of 5th metat R B ulnar ¥ D acces digit with hyperactive; epicanthic B fibular 2 phals, rud. 6th folds; VSD; CDH L metac ..or metat fused to 5th, acces has a small joint B ulnar acces perpendicular to 5th, articulates with 5th metac, L i s f a i r l y I D , R i s ¥D; B fibular L: ¥ D acces-- toe with 6th metat;. R: ¥. D acces toe, 5th & 6th metat fused at base general hypotonia; M R; slow dentition; CDH R; moderate kyphosis; cryptorchidism B ulnar acces almost at . right angle to 5th, articulates with 6th metac L, with b i f i d 5th metacarpal R; B fibular ¥ D acces: L a r t i -culates with 5th metat, R 6th metat fused to base of 5th; R: medial deviation of distal phal of great toe L ulnar B fibular pedicle L: ¥ D acces, 5th & 6th metat fused at base; R: acces less ¥ D, bone fragment lateral aspect head of 5th metatarsal Laurence-Moon-Biedl syndr d i f f i c u l t y with eyesight Laurence-Moon-Biedl syndr mild M R; triencephaly;" r e t i n i t i s pigmentosa; hirsute; mild gynecomas-t i a ; obesity; diabetis insipidus; hypogonadism, cryptorchidism L; broad spatulate fingers misc. at approx 23 weeks L hand 189 Birth Ethnic Mat. Pat. Source of _ m f orm Ba — 31 — MRec 10 Mar 67 JMT M . . o f ^ r c e Birthdate Proband Sex Pedigree place origin age age inform. o •o 128 L Ind (21) — MRec 22 Apr 67 MM M 6 - i~6 129 K Ind 25 — MRec 2 Apr 67 RL M O P M o - • 130 6 6%Tb Gc NInd 40 44 MRec 27 Apr 65 AB M ' CD-EC J -o 131 • cY m Be — 26 — MRec 23 Jul; 64 HMH M O O 132 Proband Position _ ... „ ,. . , i n . . Description of supern. digits number pedigree _ _ 1 3 3 I I 1 2 R hand extra digit Additional anomalies cerebellum somewhat small; receding chin; CHD: i n t e r -v entricular septal 'defect, unusual globular shape; abn. multilobulated l i v e r ; cryptorchidism; protuber-ant heels and rockerbottom appearance of feet • I I - birthmark on neck and arm 1 3 4 I I .33 hands pedicles, t i e d off tongue-tie 2 135 I I R foot acces phal attached to metac; t i n y n a i l 8 136 I I ' B feet . abn. buttock crease I I 7 ? polyd . B feet 137 I I 5 B feet 138 I I polyd extra d i g i t s B c l e f t l i p and c l e f t palate; abn. penis and scrotum 191 Birth Ethnic Mat. Pat. Source _. , , „ , , „ . . or„ Birthdate Proband Sex place origin age age inform. Be NInd 45 53 MRec 7 Nov 67 L M+ DCJ Pedigree 133 _ 6 _ ' 6 _ 6 6 _ 4 _ -+ Bb Nb Ba Bb 24 22 MRec 18 Jun 66 LDH P D" -o MRec 14 Oct 64 WP M /-N Ur~ r — O — r O MRec 25 Jan 64 TCS M PHN 6 i7> 37 6 6 6 6 66 6* MRec 28 Jun 65 ECT M J MRec 1 Jul 66 ' N .' M' »—•—I ^ — [ — -6 P 6~_ 134 135 136 137 138 1 92 Appendix B Dermatoglyphics In many cases dermal ridges i n the immediate area of•attachment of an accessory digit are sufficiently characteristic to determine Polydactyly had been present at birth even though the digits themselves have been removed (Cummins, 1926; Cummins & Midlo, 1943; Temtamy, 1966b). An accessory d i g i t a l triradius can nearly always be distinguished i n cases of ulnar Polydactyly. This triradius i s closely associated with the site of attachment of the super-numerary finger; and from i t s placement, the breadth of the concentric dermal ridges spanning the site of attachment, and the relationship of this pattern to the major lines of the hand inferences can be made regarding the extent of duplication of the accessory. Plate 1 shows the typical dermal pattern associated with a rudimentary pedicle whereas patterns given i n Plate 2 reflect the presence of a well-formed supernumerary f i f t h finger. Well-formed and pedicle-type accessory fibular digits (Plate 3) have associated dermal patterns similar to their postaxial counterparts on the hands. In addition duplication may be polysyndactylous, i n which case an accessory triradius w i l l probably not be present. Preaxial Polydactyly may also be polysyndactylous, well-formed or of-a pedicle nature. Plate 4 presents the print of a polysyndactylous thumb prior to surgery. The pattern on the tip of the thumb extends across both fingertips; the distal bifurcation i s aligned with the common triradius. This can be com-pared to the dermal pattern associated with nonsyndactylous duplication of the thumb, the accessory thumb arising off the proximal phalanx of the principal f i r s t d i g i t . The l e f t hand and right' foot of a child with polysyndactyly are i l l u s t r a -ted i n Plate 5. Prior to surgery t i b i a l Polydactyly was present, however derma-toglyphic features associated with the site of attachment or bifurcation have been obliterated. Clearly seen i n the foot print i s syndactyly of toes one through three. An accessory triradius resulting from ulnar Polydactyly is apparent in the hand print as well as syndactyly of fingers three and four and a very broad thumb. Plate 1. Dermatoglyphics of Ulnar Polydactyly Postminimi Left above: small scar remaining after postminimus tied off (proband number 76) Right above: triradius of accessory digit off proximal phalanx (proband number 119) Left: triradius of accessory digit off medial phalanx (proband number 55) Plate 2. Dermatoglyphics of Ulnar Polydactyly Well-formed, articulating digits • .fe-r Above: triradius of to triradius number 131) Left: triradius of to triradius number 131) accessory digit d i s t a l of 5th finger (proband accessory digit proximal of 5th finger (proband 196 Plate 3. Dermatoglyphics of Fibular Polydactyly Above: t r i r a d i u s of accessory d i g i t o f f proximal phalanx (proband number 97) Right: t r i r a d i u s of lateral-most toe proximal to t r i r a d i u s of the numerically 5th toe (proband number 127) . •."•..At-.i . V mm - •••• S B 1 * L e f t : t r i r a d i u s of the lateral-most toe dominates the t r i r a d i u s of the numerically 5th toe (proband number 131) Plate 4. Dermatoglyphics of Radial Polydactyly Left above: detail of thumb print of hand right; the pattern extends across both finger tips with the triradius and bifurcation aligned (proband number 3) Right above: triradius of accessory digit off proximal phalanx (proband number 1) Right: duplicated di s t a l phalanx, both dis t a l phalanges present (proband number 3) Plate 5. Dermatoglyphics of Polysyndactyly Hand: triradius of supernumerary digit at base of 5th finger, syndactyly of fingers 3-4, broad thumb (IT , pedigree number 78) Foot: dermatoglyphic features of duplicated f i r s t toe.obliterated, syndactyly of toes (IV , pedigree number 78) £ co 199 Appendix C. Part A. References for Cases with Trisomy E (17-18) Syndrome 1 Edwards et a l . , 1960 2 Smith et a l . , 1960 ^ I! 11 4 Crawfurd, 1961 5 Brodie and Dallaire, 1962 6 German et a l . , 1962 6 fingers ? B hands 8 Gottlieb et a l . , 1962 9 " " 10 Koenig et a l . , 1962 1 •] II II 12 Rosenfield at a l . , 1962 13 Smith et a l . , 1962 14 ii it 15 11 11 16 " " -17 II M 18 Townes et a l . , 1962b 19 Uchida et a l . , 1962a 20 " " 21 " " 22 " " 23 n " 24 Uchida et a l . , 1962b 25 Pinley et a l . , 1963 26 Hansen et a l . , 1963 Part A. (continued) 27 Haylock et a l . , 1963 . 28 " " " 29 Holman et a l . , 1963 30 " " 31 Rohde et a l . , 1963 32 Steinberg and Jackson, 1963 33 Trowell and Hilton, 1963 34 Wagshal-Ives and Berman, 1963 35 " " 36 " " 3Y II II 38 Burks and Sinkford, 1964 39 Levkoff et a l . , 1964 40 Lewis, 1964 41 " " 42 " " 43 " " 44 Marden et a l . , 1964 45 Pfeiffer, 1964 46 '.' " 47 Rohde et a l . , 1964 48 Turner et a l . , 1964 49 Voorhess et a l . , 1964 50 Zellweger, 1964 51 Lewis and. Paint, 1965 52 Hook et a l . , 1965 53 Hook and Yunis, 1965 Part A. (continued.) 54 Weichsel and Lu z z a t t i , 1965 55 Windmiller et a l . , 1965 56 Taylor, 1968 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 6 d i g i t s B hands 6 d i g i t s L hand 202 Part A. (continued) 81 Taylor, 1968 82 Benady and Harris, 1969 83 " " 84 " " 85 " " 86 " " 87 Chesler et a l . , 1970 88 Medical Genetics, U.B.C., No. 63-4 B ulnar acces. digits 89 90 91 92 93 94 95 96 97 98 99 100 No. 65-6 . No. 65-96 No. 66-74 No. 67-63 • No. 67-123 No. 67-128 No. 67-170 No. 69-8 No. 69-23 No. 69-239 No. 70-79 No. 70-147 203 Part B. References for Cases with Trisomy D.^  Syndrome ^ o Type of duplication  polyd. ulnar • fibular t i b i a l unk. 1 Patau et a l . , 1960 L 2 Atkins & Rosenthal,,1961 L L 3 E l l i s & Marwood, 1961 L L 4 Lubs et a l . , 1961 ".. B L 5 Patau et a l . , 1961 + 6 " " L 7 Therman et a l . , 1961 L 8 Buhler et a l . , 1962 B 9 Northcutt, 1962 L L 10 Rosenfield et a l . , 1962 + 11 Townes et a l . , 1962a B R 12 Miller et a l . , 1963 B R 13 Sergovich, 1963 L + 14 Smith et a l . , 1963 + 15 " " L 16 " " + 17 Warburg & Mikkelsen, 1963 • ' R 18 Blanck et a l . , 1964 • B 19 Lafourcade et a l . , 1964- + 20 Marin-Padilla, 1964 + 21 " " B B 22 Pfeiffer, 1964 B B 23 II it + 24 " " B 25 Powars et a l . , 1964 B B 204 Part B. (continued) 26 Taylor & Polani, 1964 27 II it 28 " " 29 Eewis & Paint, 1965 30 Mehes & Bata, 1965 31 Mottet & Jensen, 1965 ^2 II '• ^3 II it 34 Snodgrass et a l . , 1966 35 " " 36 " " •yj it M 38 " " 39 ti it 40 " " 41 Wilson & Melnyk, 1967 42 Butomo & Shushval, 1968 43 Taylor, 1968 44 " » 45 ti 'i 46 " " 47 II I' 48 " " 49 it tt 50 " " 51 " " No polyd. ulnar fibular t i b i a l unk. + + + + + + + + B B B B B B B B R B B U 52 + Part B. (continued) Wo polyd. ulnar, f i b u l a r t i b i a l unk. 205 53 Taylor, 1968 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 Toews & Jones, 1968 70 Wilson, 1968 7-] 11 11 72 " •' 73' James et a l . , 1969 74 " 'I 75 11 11 76 " " 77 11 it 78 " " + + + + + + B(7th) B L B B L B B B B R B L(7th) B B B + + + + + + 79 206 Part B. (continued) Wo polyd. ulnar : f i b u l a r t i b i a l unk. 80 James et a l . , 1969 + 81 Bowen et a l . , 1970 L L 82 Taylor et a l . , 1970 + 83 " " + 84 " " + 85 Thorburn, 1970 + 86 " " + 87 II ii + 88 " " + 89 " " + go 'I 'i + 91 Yu et a l . , 1970 B 92 " " B 93 i. II L B 94 " " L B 95 Medical Genetics, U. B. C , Wo. 62-105 B 96 "' " , Wo. 62-132 B L 97 " " , Wo. 63-34 B R 98 " " , Wo. 68-11 L 99 B. C. study, proband no. 43 L 100 B. C. study, proband no. 46 L 101 B. C. study, proband no. 70 B 207 Part C. References for Cases with Polydactyly/imperforate Anus/Vertebral Anomalies Syndrome and Cases with Similar Anomalies 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Puhrmann, 1968 Say and G-erald, 1968 ii it it Tunte, 1968 Millard, 1969 Kaufman et a l . , 1970 Townes and Brocks, 1970 Imperforate anus + + + + + + + + + + + + + + + + + + + + + Anomalies di g i t a l vert'eb. rib other + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 25 + 208 Part C. (continued) „ Anomalies Imperforate anus d i g i t a l verteb. rib other 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Say et a l . , 1971 Stieve, 191' Keel, 1958 Stevenson et a l . , 1966 Temtamy, 1 966b Tan, 1969 Reid and Woolf, 1970 B.C. study, proband no. 124 + + + + + + + + + + + + + • + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 0 + + + + + 0 + + + + + + + + + + + + + + + + + + + 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            data-media="{[{embed.selectedMedia}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
https://iiif.library.ubc.ca/presentation/dsp.831.1-0101922/manifest

Comment

Related Items