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

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POLYDACTYLY IU BRITISH COLUMBIA 1964 -  1967  by DARYL CHRISTINE JONES B.Sc,  Portland State U n i v e r s i t y , 1969  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN GENETICS i n the D i v i s i o n of Medical Genetics  We accept•this t h e s i s as conforming to the required standard  THE UNIVERSITY OP BRITISH COLUMBIA SEPTEMBER 1971  In presenting t h i s thesis in p a r t i a l fulfilment of the requirements for an advanced degree at the University of B r i t i s h Columbia, I agree that the Library shall make i t freely available for reference and  study.  I further agree that permission for extensive copying of this thesis for scholarly purposes may by his representatives.  be granted by the Head of my  It is understood that copying or publication  of this thesis for financial gain shall not written  permission.  flopartmcirt of  7/lAs./s,&df, Mztclfce-/^  The University of B r i t i s h Columbia Vancouver 8, Canada.  Date  Jf  fQf.U^  /IM  Department or  be allowed without  my  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  i n the province i n the years 1964 - 1967 were ascertained p r i n c i p a l l y through the Registry f o r Handicapped Children and Adults; additional cases were foundthrough disease indexes of B.- C. hospitals and through r e f e r r a l s from medical personnel.  Data on the probands were obtained by family interviews and review  of various medical records.  Information  compiled f o r a case included:  sex of  proband, r a c i a l background, parental age, p a r i t y of mother, notes on the pregnancy, d e s c r i p t i o n of accessory d i g i t s , genetic family history, and nature of. additional congenital anomalies when rpresent. Incidence births.  of Polydactyly i n B.C. f o r 1964 - 1967 was 1.02 per 1,000 l i v e  This figure includes patients with multiple congenital anomalies.  the four years covered by the study, 1966 had the highest incidence (1.35),  Of a  year i n which a seemingly disproportionate number of ulnar cases occurred. Ninety-five males and 43 females, a sex r a t i o of approximately 2 : 1 , the following types of duplication:  r a d i a l (31), t i b i a l  f i b u l a r ( 2 4 ) and ulnar and f i b u l a r (16).  presented  (6), ulnar (54),  I t i s proposed that cases with both  ulnar and f i b u l a r accessory d i g i t s and cases with ulnar or f i b u l a r  accessory  d i g i t s i n whose family both ulnar and f i b u l a r duplication occur present ulnarf i b u l a r type Polydactyly.  Based on cases unassociated with multiple congenital  anomalies, s p e c i f i c types of Polydactyly had the following incidences:  radial  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 ulnarf i b u l a r , 0.09. Genetic h i s t o r i e s  indicate i n 32 families out of 138 there i s another i n -  d i v i d u a l with Polydactyly.  For s p e c i f i c types of Polydactyly the following  proportion of cases without multiple congenital anomalies had a p o s i t i v e family  r a d i a l , 5 - 19 %;  history:  f i b u l a r , 73 f°~  t i b i a l , 0 %; ulnar, 29 %•  f i b u l a r , 25  and ulnar-  Polygenic inheritance of ulnar and of f i b u l a r types of Polydactyly  i s suggested by the f i n d i n g that the percentage of affected sibs i s greater when there i s a h i s t o r y of Polydactyly i n previous generations than f o r probands with a negative h i s t o r y (1.2 fo).  (approximately 6.6 fo)  The number of affected sibs  of the probands (3/107) i s i n agreement with the number which would be for a polygenic t r a i t .  expected  Data f o r u l n a r - f i b u l a r Polydactyly i s 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 t h e i r c h i l d r e n whereas such an occurrence i s unknown f o r males. . Among u l 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 % 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 population.  Multiple major anomalies are approximately  25 times more frequent.  A polydactylous c h i l d found to have one major malformation  i s twice as  likely  to have a d d i t i o n a l major anomalies than a c h i l d with one major anomaly who the normal number of d i g i t s .  has  Multiple congenital anomalies were most commonly  seen with u l n a r - f i b u l a r Polydactyly.  This may r e f l e c t the fact that ulnar-  f i b u l a r d u p l i c a t i o n i s the type most commonly seen as a feature of various syndromes. In addition to the B.C. reviewed.  Included are:  findings, l i t e r a t u r e on Polydactyly has been  data on the incidence of Polydactyly i n other popu-  l a t i o n s , d e s c r i p t i o n of d i f f e r e n t types of duplication, hypotheses regarding the inheritance of accessory d i g i t s , tabulation of the types of Polydactyly seen i n various syndromes, and discussion of the morphogenesis of accessory d i g i t s i n r e l a t i o n to limb embryogenesis.  iii Contents I.  II.  III.  IV.  V.  VI.  Introduction  1  A.  Purpose of study  1  B.  Embryology  2  Methods  9  A.  Ascertainment  9  B.  Follow-up  11  C.  Incidence  13  D.  R a c i a l background of probands  13  E.  Parental age  14  P.  B i r t h order of the probands  15  G.  Extent of d u p l i c a t i o n  15  H.  Genetic f a m i l y h i s t o r y  16  I.  M u l t i p l e congenital  16  anomalies  Geographical D i s t r i b u t i o n  18  A.  18  Results and d i s c u s s i o n  Incidence  21  A.  L i t e r a t u r e 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  Parental Age and P a r i t y  33  A.  33  Results and d i s c u s s i o n  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  iv Contents  VII.  VIII.  D.  T i b i a l Polydactyly  46  E.  Polydactyly of the index f i n g e r  46  P.  Polydactyly of the t h i r d or f o u r t h f i n g e r s  48  G.  Ulnar Polydactyly  49  H.  F i b u l a r Polydactyly  50  I.  Ulnar-fibularrpolydactyly  53  J.  Polysyndactyly  54  K.  Results  54  L.  Discussion  61  Genetics  66  A.  Introduction  66  B.  L i t e r a t u r e 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:  F.  Conclusions  r e s u l t s and d i s c u s s i o n and speculation  78 '  83  M u l t i p l e Congenital Anomalies  87  A.  Introduction  87  B.  Results  88  Minor anomalies  88  Single major anomalies  90  M u l t i p l e 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  P o l y d a c t y l y / i m p e r f o r a t e a n u s / v e r t e b r a l anomalies syndrome  11 3  Laurence-Moon-Biedl  118  Smith-Lemli-Opitz  syndrome syndrome  P o l y c y s t i c k i d n e y s , i n t e r n a l hydrocephalus  1 20 and  p o s t a x i a l P o l y d a c t y l y syndrome IX. X. XI.  121  Summary  124  Literature Cited  126  Appendix A A.  - 1 4 3  Guide to d a t a r e g a r d i n g the probands and key to a b b r e v i a t i o n s and symbols  B. XII. XIII.  Case d e s c r i p t i o n s  Appendix B: Appendix C A. B. D.  143 146  Dermatoglyphics  192 .  1  9  9  References f o r cases w i t h t r i s o m y E (17-18) syndrome References f o r cases w i t h t r i s o m y syndrome  199 203  References f o r cases w i t h p o l y d a c t y l y / i m p e r f o r a t e a n u s / v e r t e b r a l anomalies syndrome and cases w i t h s i m i l a r anomalies  207  vi Tables I. II. III. IV. V.  Sources of Ascertainment and Information  10  Geographical D i s t r i b u t i o n of Probands by B i r t h p l a c e  19  Incidence  22  of Polydactyly i n D i f f e r e n t Races  Incidence of Polydactyly i n B r i t i s h Columbia, 1964 - 1967 Number of Cases of S p e c i f i c Types of Polydactyly i n  1964 - 1967 VI. VII.  26  Incidence of Polydactyly i n B r i t i s h Columbia by Month  IX. X.  XII. XIII.  34  Mean Parental Age at the B i r t h of Male and of Female Probands B i r t h Order of the Probands and of Live B i r t h s i n B r i t i s h  35 37  Hand A f f e c t e d i n Cases with R a d i a l Polydactyly  42  Frequency of Accessory D i g i t s i n Conjunction with T i b i a l Polydactyly Frequency of Accessory D i g i t s i n Conjunction with Ulnar  47  Polydactyly XIV. XV. XVI.  S i t e of D u p l i c a t i o n According  51 to Sex of the Probands  D e s c r i p t i o n of the Forms of D u p l i c a t i o n Presented by the Probands Incidence of S p e c i f i c Types of Polydactyly i n B r i t i s h Columbia  XVII. XVIII. XIX. XX. XXI.  31  Mean Parental Age at the B i r t h of the Probands  Columbia, 1964-1967 XI.  28  Incidence of Polydactyly among Males and Females i n B r i t i s h Columbia, 1964 - 1967  VIII.  25  55 58 62  Types of Polydactyly Found i n Singapore  63  Cases with a P o s i t i v e Family H i s t o r y of. Polydactyly  74  Penetrance of P o s t a x i a l Polydactyly  79  Proportion of Polydactylous O f f s p r i n g i n Families with Two or More A f f e c t e d I n d i v i d u a l s Type of Polydactyly Presented by Children with a Minor Anomaly  .82 89  vii Tables XXII.  Type of P o l y d a c t y l y Presented by Children with One Major Anomaly  91  Type of Polydactyly Presented by Children with M u l t i p l e Major Anomalies  93  XXIV.  Type of Polydactyly Associated with A d d i t i o n a l Congenital Anomalies  98  XXV.  Syndromes and Anomaly Complexes Associated with Duplicated  XXIII.  ' 1 0 0  Digits XXVI. XXVII. XXVIII.  Cardinal Features of the Newborn with Down's Syndrome  103  C l i n i c a l Features of Trisomy 17-18 Syndrome  105  C l i n i c a l Features of Trisomy D  108  1  Syndrome  XXIX.  S i 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/ V e r t e b r a l Anomalies Syndrome D i g i t a l Anomalies of the Polydactyly/imperforate Anus/  115  XXXII.  11 6  V e r t e b r a l Anomalies Syndrome 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  XXXIII.  viii Figures and Plates  Figure 1.  Plate P l a t e 2.  Map of the Province of B r i t i s h Columbia  Dermatoglyphics of Ulnar Polydactyly, Postminimi  20  177  Dermatoglyphics of Ulnar P o l y d a c t y l y , Well-formed, A r t i c u l a t i o n D i g i t s  178  P l a t e 3.  Dermatoglyphics of F i b u l a r Polydactyly  179  P l a t e 4.  Dermatoglyphics of R a d i a l Polydactyly  180  P l a t e 5.  Dermatoglyphics of Polysyndactyly  181  ix Acknowledgments  The author g r a t e f u l l y acknowledges the continued support and d i r e c t i o n of her committee chairman Dr. J . R. M i l l e r , Head of the D i v i s i o n of Medical Genetics, and committee members Dr. R. B. Dowry and Dr. C. W. Roberts. Miss A. E. S c o t t , Administrator of the R e g i s t r y f o r Handicapped C h i l d r e n and A d u l t s , 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 P r o v i n c i a l Health U n i t s , the Department of. Indian A f f a i r s , and the B. C. h o s p i t a l s and physicians who a s s i s t e d i n gathering the data i s not p o s s i b l e but t h e i r cooperation i s g r e a t l y appreciated. The author i s p a r t i c u l a r l y g r a t e f u l f o r the warm cooperation of the p a r t i c i p a t i n g f a m i l i e s who were e s s e n t i a l to the success of t h i s study and f o r the k i n d assistance of many i n d i v i d u a l s who made the f i e l d work so enjoyable. Of s p e c i a l assistance i n preparing the t h e s i s were Miss S. M. Manning, who drew out the pedigrees, Mr. D. Guthrie, who photographed the p l a t e s , 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 d u p l i c a t i o n of a d i g i t or d i g i t s , i s a hetero-  geneous anomaly occurring both on the p o s t a x i a l part of the hands or feet,; adjacent to the f o u r t h or f i f t h d i g i t s , and on the p r e a x i a l part, adjacent to the f i r s t or second d i g i t s .  Expression ranges from a complete, f u n c t i o n a l  extra f i n g e r or toe to a small s k i n tag or polysyndactylous d i s t a l phalanx.  d u p l i c a t i o n of a  D u p l i c a t i o n occurs as an i s o l a t e d e n t i t y , i n a s s o c i a t i o n with  other d i g i t a l anomalies.such as syndactyly, and as part of a number of m u l t i p l e congenital anomaly complexes, some of which are recognized syndromes.  Many  polydactylous i n d i v i d u a l s with p o s t a x i a l d u p l i c a t i o n have a f a m i l y h i s t o r y of accessory d i g i t s whereas f a m i l i a l inheritance i s uncommon among p r e a x i a l cases. A strong genetic component i n the e t i o l o g y 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 P o l y d a c t y l y , data a v a i l a b l e  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  (b)  population?  What i s the sex r a t i o among i n d i v i d u a l s with a s p e c i f i c form of Polydactyly?  (c)  What percentage of i n f a n t s with a s p e c i f i c form of Polydactyly have a p o s i t i v e f a m i l y h i s t o r y f o r the same or a d i f f e r e n t type of Polydactyly?  (d)  Do data on f a m i l i e s with two or more polydactylous i n d i v i d u a l s support the theory that p o s t a x i a l accessory d i g i t s of types A and B 1922;  (e)  (Sverdrup,  see s e c t i o n V I I , p.70) are g e n e t i c a l l y d i s t i n c t ?  How commonly i s the gene (genes) f o r Polydactyly apparently nonpenetrant among males and among females?  2  (f)  I n man does p a r e n t a l age and/or p a r i t y appear to be a f a c t o r i n the occurrence  (g)  of accessory  I s t h e r e an i n c r e a s e d f r e q u e n c y viduals with a s p e c i f i c  (h)  digits? o f major o r minor anomalies among i n d i -  type o f P o l y d a c t y l y ?  Do p o l y d a c t y l o u s i n d i v i d u a l s w i t h m u l t i p l e c o n g e n i t a l anomalies, of  some  which p r e s e n t r e c o g n i z e d syndromes, commonly have a p o s i t i v e f a m i l y  h i s t o r y of Polydactyly? The  B r i t i s h Columbia [B.C.]] P o l y d a c t y l y study on which t h i s d i s s e r t a t i o n i s  based was d e s i g n e d and  B.  additional  t o gather i n f o r m a t i o n which c o u l d be used to answer these  questions.  Embryology P r e c i s e l y what t r i g g e r s the development o f p o l y d a c t y l o u s limbs and how  t h e i r embryopathy proceeds i n man i s l a r g e l y unknown. (1930, 1942, 1945, 1948, 1949, 1951) and by Nishimura as the c h a p t e r on embryology by Barsky c h a r t i n g limb morphogenesis i n man. to  seventh  c e r v i c a l somites  12 ( s t r e e t e r ,  (1958),  Porelimb  Papers by S t r e e t e r and c o l l e a g u e s , as w e l l  are p a r t i c u l a r l y valuable i n buds, appear o p p o s i t e the f i f t h  around the 26th - 28th day of g e s t a t i o n a t H o r i z o n  1942) o r m o r p h o l o g i c a l  age 4 (Nishimura & Yamamura, 1969);  h i n d l i m b buds appear somewhat l a t e r , a t H o r i z o n 13 o r m o r p h o l o g i c a l  age 5-  C o n s i d e r a b l e v a r i a t i o n i n the e x t e n t o f development among embryos o f presumably the same c h r o n o l o g i c a l age has been noted As  (Nishimura & Yamamura, 1969).  the s m a l l r i d g e s o f t i s s u e c o m p r i s i n g the limb buds extend  distally,  t h e r e i s d i f f e r e n t i a t i o n o f a p r o x i m a l r e g i o n which w i l l form the upper p a r t of  the limb and a d i s t a l r e g i o n from which the hand o r f o o t i s d e r i v e d .  A  f l a t t e n i n g o f the d o r s a l end o f the upper limb buds which r e p r e s e n t s the hand occurs around the f i f t h week ( H o r i z o n 16-17, m o r p h o l o g i c a l  age 8 ) . Morpho-  g e n e s i s o f the hands proceeds somewhat i n advance o f the f e e t , which i s  3 compatible w i t h the observation from thalidomide embryopathy that d u p l i c a t i o n of the thumbs may r e s u l t from maternal i n g e s t i o n of thalidomide around day 34 - 38 whereas d u p l i c a t i o n of the f i r s t toes r e s u l t s from i n g e s t i o n around day 41 - 44 (Lenz, 1964).  The anlagen of the f i n g e r s 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 d o r s a l surface of the hand p l a t e (Horizon 17-18, morphological age 9).  Towards the end of the s i x t h week the  limbs p r o j e c t n e a r l y s t r a i g h t 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 p l a t e , and anlagen of the d i g i t a l rays become v i s i b l e i n the f e e t (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 d i s t i n g u i s h e d . i l l u s t r a t e d i n the 1966 paper of Wishimura et al.:  This i s  One p l a t e shows the poly-  dactylous hands of an embryo of Horizon 18 i n which there i s an excessive amount of t i s s u e 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 f e e t and the notches between the f i n g e r s have become deeper and acutely angled (Horizon 20, morphological age 11). elbow can now be seen.  A bending i n the region of the  In the seventh week there i s elongation of the d i g i t s  and separation i n t o i n d i v i d u a l f i n g e r s and toes. of the d i g i t s .  "Touch pads" form at the taps  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 f e e t .  Towards the end of t h i s period of r a p i d  morphogenesis d i g i t s two through four s i t u a t e p a r a l l e l to each other (morphol o g i c a l age 15 i n the hands, and age 16 i n the f e e t , Horizon 22-23).  The  hands of an embryo (Horizon 22) w i t h b i l a t e r a l ulnar P o l y d a c t y l y whose limbs  4  are a t approximately t h i s 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 p l a t e , c a r p a l elements begin to chondrify.  C h o n d r i f i c a t i o n i n the  d i g i t a l rays takes place around the seventh week i n ' c o n j u n c t i o n w i t h elongat 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 w i t h an accessory thumb attached a t r i g h t angles to the base of the r i g h t f i r s t metacarpal showed c h o n d r i f i c a t i o n of digital.elements i n c l u d i n g an independent "phalanx" i n the accessory thumb.  (Developmental age of the embryo has been  estimated at Horizon 22.) I t i s a l s o i n t e r e s t i n g to note that t r i p h a l a n g e a l thumbs seen w i t h thalidomide embryopathy are associated w i t h maternal ingest i o n of the teratogen around day 48 - 50 (Lenz, 1964, 1965), a t approximately the time c h o n d r i f i c a t i o n would be t a k i n g place. The f i r s t o s s i f i c a t i o n center appears a t about eight weeks i n the terminal phalanx of the thumb, followed by centers i n the second, t h i r d and f o u r t h f i n g e r s , 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 o s s i f y i n t h i s sequence.  Early  i n the eighth week the second and t h i r d metacarpals begin to o s s i f y , then the f o u r t h 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 a f t e r 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 .  A t 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 r o t a t i o n to a more v e n t r a l p o s i t i o n ( G a l l et a l . , 1966). Data i n d i c a t e o s s i f i c a t i o n begins i n the toes e a r l y i n the eighth week ( M a l l , 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 w i t h the f o u r t h and f i f t h metacarpals and the proximal phalanges of the second and t h i r d f i n g e r s .  The second,  t h i r d and f o u r t h 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, f o u r t h and f i f t h toes  then o s s i f y .  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 ( M a l l , 1906).  Ossification  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 , f o u r t h and f i f t h d i g i t s f o l l o w 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 w i t h i n 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 p r e a x i a l border of the hands and feet and t h i s period of r a p i d 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 l e a s t common.  T i b i a l and u l n a r development appears to  proceed at approximately the same time and Polydactyly of these borders i s a feature of polysyndactyly.  However the most i n t e r 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 u l n a r 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  p o s t a x i a l 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 e f f e c t a more severe malformation. V a r i a t i o n i n extent of d u p l i c a t i o n could depend l a r g e l y 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 i n t e r r u p t e d 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 f o o t ) , which continued to develop i n sequence with the other d i g i t s would be expected to develop i n t o a well-formed f i n g e r .  D u p l i c a t i o n s o l e l y 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 e r r o r and f i r s t recognizablee during segmentation of the f i n g e r s when mesenchymal condensation of c h o n d r i f i c a t i o n of accessory phalanges occurred. Regarding the formation of pedunculated  accessory d i g i t s , Cummins (1932)  f e l t that a r r e s t of growth and d i f f e r e n t i a t i o n , e s p e c i a l l y of the basal portion, was responsible f o r t h e i r p a r t i c u l a r morphology.  V a r i a b l e l o c a t i o n of ulnar  p e d i c l e s , 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 r e s u l t from e i t h e r of the f o l l o w i n g :  (a) an accessory f i n g e r 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 a t some point o f f the l a t e r a l margin of the proximal phalanx of the f i f t h f i n g e r i n the subsequent r a p i d extension of that f i n g e r ;  (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 f i n g e r bud o f f the extending f i f t h d i g i t .  I t s l o c a t i o n would therefore be  dependent upon the p a 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 p o t e n t i a l of the t i s s u e f o r f u l l development of a d i g i t could be considerably reduced i n d i r e c t proportion to the l a g i n time between i t s i n i t i a t i o n and that of the other f i n g e r s .  Following the technique of Nishimura and Yasuda (1969),  the existence of t i m e - s p e c i f i c 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 c u l t u r e s of limb buds to teratogens which induce Polydactyly. The concept of t i m e - s p e c i f i c c r i t i c a l phases i n organogenesis i s often r e f e r r e d to when d i s c u s s i n g the r e l a t i o n s h i p of a c l u s t e r 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 p r i m i t i v e heart occurs during the f o u r t h  7 to s i x t h weeks of g e s t a t i o n , c o r r e s p o n d i n g ( H o l t & Oram, 1960; postulated genesis  there  Starke  c o u l d be  et a l . , 1967;  w i t h development of the upper  Ashby et a l . , 1969).  Temtamy (1966a)  some time d u r i n g the s i x t h or seventh weeks of embryo-  a t which p o i n t d y s f u n c t i o n would i n t e r f e r e w i t h  cellular  differentiation  of the h y p o p h y s i s 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 and  extension  and  Moon-Biedl syndrome.  p o s t a x i a l P o l y d a c t y l y c h a r a c t e r i s t i c of the L a u r e n c e -  Furthermore p h e n o t y p i c o v e r l a p between t h i s syndrome  C a r p e n t e r ' s syndrome, marked however by the c o n s i s t e n t o c c u r r e n c e of P o l y d a c t y l y i n the l a t t e r , C a r p e n t e r ' s syndrome was  suggested the c r i t i c a l  earlier.  tary accessory  be  period f o r determination  questioned,  The  considering that  of the hand p l a t e occurs  the prior  the p a t i e n t w i t h p o s t a x i a l P o l y d a c t y l y  i n c l u d e d among cases of C a r p e n t e r ' s syndrome had  q u i t e rudimen-  digits.  demonstrated  In a d d i t i o n thalidomide  embryopathy has  l i n k i n g d i g i t a l defects with  m a t e r n a l i n g e s t i o n of t h a l i d o m i d e duplication  regarding  provide  other malformations.  p l a s t i c t r i p h a l a n g e a l thumbs and  anus can be  one  limbs.  t e r a t o g e n i c e f f e c t s of t h a l i d o m i d e  p l a s i a and  of  the  t h e r e can be a h i g h s p e c i f i c i t y f o r i n t e r f e r e n c e i n the morphogenesis of b o r d e r of the  and  tibial  the b a s i s of d i f f e r e n t i a t i o n of  on the u l n a r p e r i p h e r y  to t h a t of the t i b i a l b o r d e r , and 1931)  On  t h i s l a s t c o n c l u s i o n may  appearance of n o t c h i n g  (Turner,  retina,  segmentation of the d i g i t s r e s u l t i n g i n hypophyseal o b e s i t y ,  r e t i n i t i s pigmentosa, and  d i g i t s alone,  limbs  the most c o n c l u s i v e evidence  Lenz (1965) r e p o r t e d  a n o r e c t a l s t e n o s i s can both r e s u l t on day  of the thumbs and  48 - 50.  The  from  f a c t t h a t a p l a s i a , hypo-  a t r e s i a of the eosophagus and  caused by the s i n g l e agent, t h a l i d o m i d e ,  i s a l s o of i n t e r e s t  the p o l y d a c t y l y / i m p e r f o r a t e - a n u s / v e r t e b r a l  anomalies syndrome.  evidence of c o r r e l a t e d development of a c c e s s o r y  d i g i t s and  can be i n f e r r e d from f i n d i n g s of Nishimura et a l . (1966): P o l y d a c t y l y among enbryos of about t h r e e  hypo-  of  the  Further  a d d i t i o n a l defects the f r e q u e n c y of  to t e n weeks of age  was. a p p r o x i m a t e l y  8 ten times i t s incidence among newborns suggesting a common a s s o c i a t i o n with defects incompatible w i t h s u r v i v a l to term.  9 II.  Methods  A.  Ascertainment The study of Polydactyly i n the province of B r i t i s h Columbia began w i t h  cases ascertained through the B.C. Registry f o r Handicapped Adults.  Children and  This d i c t a t e d i n large measure the time span of the p r o j e c t , as 1964—  1967 were the years f o r which the R e g i s t r y had the best information on cases; 1963 had been the f i r s t year of a broader R e g i s t r y program and information f o r 1968 was not yet complete when the study began.  Cases were also ascertained  by w r i t i n g . t o h o s p i t a l s throughout the province, asking i f any c h i l d r e n w i t h Polydactyly were known to have been born or treated i n the h o s p i t a l .  This  information could e a s i l y be extracted from disease indexes kept by most hospitals. A d d i t i o n a l cases were r e f e r r e d by i n t e r e s t e d physicians and medical personnel, and from records of the D i v i s i o n of Medical Genetics, The U n i v e r s i t y of B r i t i s h Columbia [U.B.C.].  Table I summarizes sources of ascertainment and information  f o r the study. A t o t a l of 151 cases w i t h Polydactyly born i n 1964 through 1967 were ascertained.  The greatest number of cases o r i g i n a l l y came to a t t e n t i o n v i a the  R e g i s t r y (114); the remaining cases were discovered through h o s p i t a l 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 f o r a v a r i e t y 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 w i t h i n 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) d u p l i c a t i o n of r e g i s t r a t i o n ( l ) , a c h i l d r e g i s t e r e d at b i r t h and under another name l a t e r a f t e r adoption. In most cases Polydactyly was noted p r i o r to h o s p i t a l discharge of the newborn.  However i n a few cases, e s p e c i a l l y those i n v o l v i n g polysyndactylous  d u p l i c a t i o n of a minimal nature, t h i s came to medical a t t e n t i o n 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) R e g i s t r y (b) H o s p i t a l records (c) Medical Genetics, U.B.C. . (d) R e f e r r a l s  114 30 5 2 total  2.  Cases dismissed due to (a) B i r t h outside the province (b) Wo P o l y d a c t y l y (c) D u p l i c a t i o n of r e g i s t r a t i o n  6 6 1 total  3. II.  Number of probands i n the study  TS 138  Follow-up interviews w i t h f a m i l i e s 1.  No contact with parents or p h y s i c i a n  2.  Parents contacted (a) U n w i l l i n g to be interviewed (b) Interviewed (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 i n t e r v i e w (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 (e) P o l y d a c t y l y unknown to parents, not interviewed  3.  III.  T5T  13 9 82 6 3 total  1 T5T  P h y s i c i a n only contacted (a) Advised f a m i l y not be interviewed (b) Family moved outside of province (c) Family could not be l o c a t e d (d) Family p r e v i o u s l y seen i n Genetics C l i n i c  1 4 16 4  total  .24  Review of medical records 1.  Information from P u b l i c Health Nurse  4  2.  Consultation through Genetics C l i n i c  6  3.  H o s p i t a l records regarding (a) D e l i v e r y (b) D e s c r i p t i o n of supernumerary d i g i t s  134 131  11 recorded a t the time of surgery.  As i t was possible f o r a c h i l d with.Polydactyly  to come to a t t e n t i o n through a v a r i e t y of sources and at any point from b i r t h to the age of approximately 2-g- to 6-g-, ascertainment f o r the, population i s thought to be quite complete.  B.  Follow-up Cases ascertained through the R e g i s t r y were followed-up v i a the P u b l i c  Health Units throughout the province.  A l e t t e r was sent to the d i r e c t o r of  each u n i t informing the h e a l t h u n i t of the study and requesting that parents and family p h y s i c i a n of probands i n t h e i r area be contacted i n order to acquaint them with the study and secure t h e i r p a r t i c i p a t i o n . relayed one of the f o l l o w i n g : to take part i n the p r o j e c t , (unknown),  The health u n i t then  (a) p h y s i c i a n and/or f a m i l y w i l l i n g ( u n w i l l i n g ) (b) 'family moved, forwarding address enclosed  or (c) f a m i l y unknown to the u n i t .  Some f a m i l i e s who were unknown or whose address was unknown to the respective h e a l t h u n i t s could be followed-up i n the same manner as cases ascertained through h o s p i t a l indexes.  For these cases a l e t t e r was w r i t t e n to one of the  attending physicians or the f a m i l y p h y s i c i a n informing him of the study and seeking h i s permission to contact the parents.  Often the p h y s i c i a n discussed  the project, w i t h the parents before r e p l y i n g and i t was a pleasant s u r p r i s e to l a t e r f i n d the f a m i l i e s knew about the study and were i n t e r e s t e d .  Families  p r e v i o u s l y 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 f a c t o r y since  o c c a s i o n a l l y physicians or health u n i t s f a i l e d to r e p l y .  were exceptions however.  satisThese  Often several attempts were made by the p u b l i c health  nurses, physicians, and the i n v e s t i g a t o r to locate and contact a proband's f a m i l y with the f o l l o w i n g r e s u l t s .  In 13 cases the respective health u n i t was  12  not able to l o c a t e the f a m i l y and i t was not possible to contact the family physician.  These probands included f i v e given up f o r adoption.  the parents ( 1 0 0 ) or the p h y s i c i a n only ( 2 5 ) were contacted.  In 125 cases  Parents of nine  probands.out of 100 were u n w i l l i n g to p a r t i c i p a t e and the p h y s i c i a n of an a d d i t i o n a l c h i l d advised that the f a m i l y not be disturbed. probands were interviewed i n t h e i r homes ( 7 2 ) , by telephone  (9).  of the province.  Families of 82  at the l o c a l h e a l t h u n i t ( l )  or  In seven other cases f a m i l i e s were known to have moved out The mother.of another proband was unaware her c h i l d had  P o l y d a c t y l y and no i n t e r v i e w was attempted.  had  The i n v e s t i g a t o r was not able to  l o c a t e and/or contact the remaining f a m i l i e s ( 2 5 ) even though s i x of these had p r e v i o u s l y been located and i n d i c a t e d i n t e r e s t 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 f o r f a m i l i e s since most could be i n t e r e s t e d i n p a r t i c i p a t i n g once they were contacted. Interviews were arranged w i t h f a m i l i e s w i l l i n g to p a r t i c i p a t e by e i t h e r 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 f a m i l y were home i n order to obtain on everyone, sometimes i n c l u d i n g grandparents.  dermatoglyphics  In the course of an i n t e r v i e w  the f a m i l y was asked to describe the proband's supernumerary d i g i t s , the supernumerary d i g i t s of any r e l a t i v e s , and a genetic f a m i l y h i s t o r y was i n c l u d i n g d e t a i l s regarding the pregnancy.  taken  Most v i s i t s l a s t e d one to two  hours. H o s p i t a l s were contacted p r i o r to the i n v e s t i g a t o r ' 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 h o s p i t a l charts of the mother and proband supplemented data obtained i n the i n t e r v i e w , and comprised the bulk of information on f a m i l i e s which were not interviewed.  P u b l i c h e a l t h nurses and nurses f o r 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 f a m i l i e s as were records from the D i v i s i o n of Medical Genetics, U.B.C. Addresses were obtained f o r three f a m i l i e s which had moved out of the province.  I t was decided to see whether a genetic h i s t o r y could be constructed  f o r these probands from d e t a i l s o f f a q u e s t i o n a i r e . f i r s t l e t t e r so questionaires and dermatoglyphic families.  Unfortunately none were returned.  Parents responded to the  materials were sent to the  A second l e t t e r was received  from two f a m i l i e s however which suggests a l e s s complex form might have been successful.  C.  Incidence Incidence has been c a l c u l a t e d according to b i r t h d a t e of the probands  with information on the t o t a l number of b i r t h s i n the province taken from the 93rd ( 1 9 6 4 ) , 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 H o s p i t a l Insurance.  D.  R a c i a l background of probands Information on r a c i a l background of the probands was obtained from the  parents, medical records of h o s p i t a l s and the p u b l i c h e a l t h s e r v i c e , and the R e g i s t r y (see Appendix A).  Of greatest value was R e g i s t r y data regarding  Indian parentage (Indians native to western North America) which was a v a i l a b l e f o r most probands.  Since t h i s information i s s p e c i f i c a l l y requested on the  R e g i s t r y form, probands whose r a c i a l background was unknown have been assumed to be of non-Indian parentage. Census f i g u r e s taken i n 1961 (1961 Census of Canada, Catalog 92-553, s e r i e s 1 . 3 - 2 , Table 82) do not give an a n a l y s i s of population by r a c i a l background, but t h i s can be i n f e r r e d from information on ethnic o r i g i n .  The  14 f o l l o w i n g 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: Eskimo  native Indian and  2.3 fo, A s i a t i c 2.6 fo, other and not stated 1.8 fo, and European  ( i n c l u d i n g 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 e x t r a c t i o n ) ; Negros would appear to account f o r l e s s 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 a n a l y s i s of r a c i a l back-  gound has been equated w i t h Caucasian.  Figures used i n c a l c u l a t i n g 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  f o r 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 w i t h i n a f i v e - y e a r span, such as 25 - 29.  MidpoBnt of each f i v e - y e a r span was taken  f o r ' c a l c u l a t i o n s of mean paternal age: years.  f o r ages 25 - 29 t h i s would be 27  The f i g u r e s of 67 and of 18 years have been used f o r men whose age  was l i s t e d as greater than 65 or l e s s 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 t h i s c o n t r o l data i s not f i g u r e d from the midpoint of a f i v e - y e a r span.  15 F.  B i r t h order of the probands P a r i t y of the mother was a v a i l a b l e from medical records i n most cases as  w e l l as being supplied i n the f a m i l y interviews (see Appendix A). data on b i r t h s i n the province was taken from the 1964  - 1967  Control  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 l i v e b o r n c h i l d r e n according to maternal age.  G.  Extent of d u p l i c a t i o n D e t a i l s on the extent of d u p l i c a t i o n were obtained from various sources  with a minimal amount of c o n f l i c t i n g data.  When a v a i l a b l e , d e s c r i p t i v e 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 s u r g i c a l procedure summaries i n h o s p i t a l charts. In some instances these reports r e f l e c t e d meticulous a t t e n t i o n to the vascular, muscular and s k e l e t a l components of the duplicated f i n g e r s and/or toes.  How-  ever i t was not unusual f o r d i g i t s l i g a t e d p r i o r to h o s p i t a l discharge of the newborn to receive only a b r i e f comment, perhaps tucked among the nurses notes: "extra f i n g e r s t i e d o f f " i n a.m.  on day four.  Such rudimentary forms might  be f u r t h e r described as a " s k i n tag" .or "pedicle"; no d i s t i n c t i o n i s made between the two i n t h i s study since i t i s not p o s s i b l e to know what an i n d i v i dual p h y s i c i a n i n f e r s by each term. In nearly a l l f a m i l i e s interviewed, the parents saw the i n f a n t ' s extra digit(s).  Thus parents were able to give t h e i r observations of the  d i g i t ( s ) such as:  accessory  r e l a t i v e s i z e , l o c a t i o n perpendicular or h o r i z o n t a l to the  other d i g i t s , . s u g g e s t i o n of bony or c a r t i l a g i n o u s 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  f a m i l y 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 i g i t and i t s r e l a t i o n s h i p to the scar that  16  remained (see Appendix B).  In a d d i t i o n to interviews with f a m i l i e s and a  review of h o s p i t a l records, f o r some cases information was obtained by cont a c t i n g a family's p h y s i c i a n or the p u b l i c h e a l t h nurses. A summary of the information gathered i s provided i n Appendix A.  Organi-  z a t i o n of the cases according to form of d u p l i c a t i o n has been as objective as possible.  Where confusion-exists regarding the extent of d u p l i c a t i o n , the  tendency i s to (classify the case "unknown".  H.  Genetic f a m i l y h i s t o r y  ..  A genetic f a m i l y h i s t o r y was taken f o r the f a m i l i e s interviewed by the i n v e s t i g a t o r and was a v a i l a b l e on f a m i l i e s seen p r e v i o u s l y i n Genetics (see Appendix A).  Clinic  For the remaining probands a pedigree has been constructed  as f u l l y as p o s s i b l e from h o s p i t a l and p u b l i c h e a l t h records.  These records  r a r e l y contain information regarding the presence of Polydactyly i n other f a m i l y members. Consequently pedigrees derived from medical records i n which no a d d i t i o n a l f a m i l y members are noted to have Polydactyly may a c t u a l l y have a p o s i t i v e h i s t o r y f o r supernumerary d i g i t s .  C a l c u l a t i o n s on the percentage  of probands with a p a r t i c u l a r type of d u p l i c a t i o n who have a f a m i l y h i s t o r y of Polydactyly are baseid only on the f a m i l i e s which have been interviewed.  I.  M u l t i p l e congenital anomalies Occasi'ib.:nia;lly anomalies i n a d d i t i o n to Polydactyly were noted i n various  records on the probands.. A d d i t i o n a l 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 f o r hands and f e e t , the probands of f a m i l i e s interviewed were not examined by the i n v e s t i g a t o r i n t h i s study.  Anomalies enumerated i n Appendix  A were taken i n most cases from h o s p i t a l charts or other medical records; i n only a few cases d i d a defect come to a t t e n t i o n s o l e l y during the interview  w i t h the parents.  As no s p e c i a l measures were taken to determine  additional  anomalies among the probands, the f i n d i n g s represent a minimum estimate of the frequency of other anomalies among polydactylous c h i l d r e n .  18  III. A.  Geographical D i s t r i b u t i o n Results and d i s c u s s i o n Geographical d i s t r i b u t i o n by b i r t h p l a c e 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 b i r t h s does not appear to deviate from that of the  general  population and c l u s t e r a n a l y s i s was not attempted. I t was i n t e r e s t i n g to l e a r n that one family with a h i s t o r y of supernumerary d i g i t s r e s i d i n g 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 p i r a t e who had l i v e d on the coast of Vancouver Island. no success.  E f f o r t s were made to trace the account f u r t h e r but with  None of the probands appeared to be d i r e c t l y r e l a t e d 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.  19 Table I I . Geographical D i s t r i b u t i  City  No. of cases  Vancouver Island  of Probands by B i r t h p l a c e  City  No. of cases  Central I n t e r i o r Area  Campbell River  2  Fort S t . John  3  Tofino  1  Dawson Creek  3  Port A l b e r n i  2  Prince George  12  Nanaimo  2  Burns Lake  1  Duncan•  3  Williams Lake  3  Victoria  8*  Coastal Area Prince Rupert  1  Terrace  1  Kitimat  1  Powell River  1  Vancouver  37  North Vancouver  7  Burnaby  5  New Westminster Surrey  South Central Area Kamloops  7  Merritt  1  Salmon Arm  1  Vernon  2  Penticton  3  South Eastern Area Grand Forks  1  9  Nakusp  1  6  Castlegar  2  Nelson  2  Fraser V a l l e y Haney  4  Creston  1  Langley  1  Kimberley  1  Mission  1  Chilliwaek  2  ^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 °  IO A> JO *0  Scolt  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 i n t e r e s t due to the heterogeneous e t i o l o g y of the defect.  The incidence of Polydactyly found i n a num-  ber of previous studies i s given i n a b r i e f l i t e r a t u r e review f o r comparison with the B.C. f i n d i n g s . Incidence i n B.C. i s presented i n t h i s s e c t i o n by year and month, by r a c i a l o r i g i n , and by sex.  The incidence of s p e c i f i c types  of accessory d i g i t s appears i n the s e c t i o n p e r t a i n i n g to the various forms of Polydactyly.  A.  L i t e r a t u r e review Incidence of Polydactyly has been found to vary between d i f f e r e n t r a c i a l  groups and subgroups.  Findings from quite comparable studies on d i f f e r e n t  populations are given i n Table I I I . Pooling data from these studies gives the f o l l o w i n g incidence per 1,000 b i r t h s according to race:  Negro (11 -9), [East]  Indian (1.25), Chinese (1.15), Malay (1.05), Japanese (1.02) and Caucasian (0.90).  These f i g u r e s tend to obscure v a r i a t i o n i n incidence between people  native to d i f f e r e n t 'geographical areas or of d i f f e r e n t ethnic background. Handforth (1950) studied a Chinese  p r i s o n population and found the  lous i n d i v i d u a l s were a l l native to Kwangtung province.  polydacty-  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 r e s u l t s of separate studies on the incidence of Polydactyly are not always d i r e c t l y comparable. incidence estimates.  Several f a c t o r s may contribute to v a r i a t i o n i n  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 -  c a t i o n , may not be noted i n an i n f a n t ' s chart r e s u l t i n g i n cases missed when ascertainment  i s through medical records.  cases with rudimentary  A study may s p e c i f i c a l l y  exclude  s k i n tags, cases which have congenital anomalies i n  Table I I I .  Incidence of Polydactyly i n D i f f e r e n t Races  Reference  Locality  Race  Affected/N  Incidence per 1,000 b i r t h s  Tan  (1969)  Singapore  Malay  5  /  4,741  1.05  Tan  (1969)  Singapore  [East!] Indian  3  /  2,390  1 .25 ( l i v e b i r t h s )  Tan  (1969)  Singapore  Chinese  34  / 28,879  1.15  (live births)  Japan  Japanese  57  / 49,645  1.15  (? l i v e & s t i l l b i r t h s )  Japan  Japanese  60  / 64,569  0.93  (live & s t i l l births)  Uganda  Negro  29  /  2,068  14.0  (1963)  U.S.A.  Negro  27  /  2,523*  10.68 ( l i v e & s t i l l b i r t h s )  Chung & Myrianthopoulos  U.S.A.  Negro  217  /  16,959  12.8  Saldanha  (1964)  Brazil  Negro  23  /  3,286  7.0  (live births)  Saldanha  (1964)  Brazil  Mulatto  20  /  3,804  5.2  (live births)  Saldanha  (1964)  Brazil  Caucasian  38  / 15,532  2.4  (live births)  Switzerland  White  20  / 50,147  0.40  (? l i v e & s t i l l b i r t h s )  Sweden  Caucasian  30  / 44,  0.68 ( l i v e & s t i l l b i r t h s )  Chung & Myrianthopoulos  U.S.A.  White  23  /  (1963)  U.S.A.  White  5  /  (1943)  Mitani  Neel  (1958)  Simpkiss & Lowe Mellin  (1968)  Ehrat Book  (1948)  (1951)  (1958)  Mellin  Note:  (1961)  109  16,385. 3,215**  1 .4  (live births)  (live & s t i l l births)  (live & s t i l l births)  (live & s t i l l births)  1 .56 ( l i v e & s t i l l b i r t h s )  Cases of Polydactyly with a d d i t i o n a l congenital anomalies are included except i n the studies of Simpkiss & Lowe (no polydactylous infants with a d d i t i o n a l 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 a d d i t i o n to Polydactyly, and s t i l l b o r n i n f a n t s 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 b i r t h s i n Baltimore, F r a z i e r (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 f a c t o r as cases were ascertained 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  s k i n tags ( u l n a r ) , the most common form of Polydactyly among Negros, were often not recorded.  S i m i l a r l y i n a N i g e r i a n study (Gupta, 1969), Polydactyly  was considered an anomaly only when a phalanx and n a i l were present and cases with m u l t i p l e anomalies were classed under the major malformation. As a r e s u l t 12 out of 4,220 newborn i n f a n t s were l i s t e d as having Polydactyly, an incidence of 9.7 compared to the f i g u r e of 14.0 found by Simpkiss and Lowe (1961) i n Kampala. I t i s p o s s i b l e b i r t h s among a small proportion of the population, such as Negro b i r t h s , include most polydactylous newborns. York by B i c k (i960).  This was found i n New  In h i s studymPuerto Ricans accounted f o r the l a r g e s t  percentage of the population (58 fo) compared to White (21 %) and Negro (23 %) components, but s i x out of nine i n f a n t s with Polydactyly among 5,000 newborns were Negro. Incidence among Japanese, Chinese and Caucasian people i s approximately the same, however the form of d u p l i c a t i o n commonly seen v a r i e s .  Thumb Poly-  dactyly i s most often presented by O r i e n t a l i n f a n t s (Tan, 1969; Handforth, 1950; Stevenson et a l . , 1966) whereas the p o s t a x i a l border i s u s u a l l y affected among Caucasians (Stevenson et a l . , 1966). l i t e r a t u r e on t h i s l a s t point.  C o n f l i c t i n g data i s found i n the  This appears to r e s u l t from the means of as-  24  certainment i n i n d i v i d u a l s t u d i e s . s u r g i c a l cases t h e rudimentary  O b v i o u s l y i f p a t i e n t s a r e a s c e r t a i n e d as  s k i n t a g forms o f P o l y d a c t y l y w i l l be missed,  and t h e g r e a t e s t p r o p o r t i o n o f these a r e  B.  I n c i d e n c e i n B r i t i s h Columbia  postaxial.  by y e a r , 1964 - 1967  A t o t a l o f 138 p o l y d a c t y l o u s i n f a n t s b o r n i n B.C. i n the y e a r s 1964 1967  were a s c e r t a i n e d ( r e f e r t o l i n e 3 o f T a b l e i ) .  y e a r i n T a b l e IV and the i n c i d e n c e computed. 1967  among l i v e b o r n i n f a n t s i s 1.02 p e r 1,000.  when s t i l l or  1 .01  births*  B i r t h s a r e s e t out by  I n c i d e n c e over the y e a r s 1964 T h i s v a l u e changes v e r y  (20+ weeks g e s t a t i o n ) a r e i n c l u d e d :  p e r 1,000 newborns.  little  138 out o f 136,730  Only one o f the probands i s known t o have been  stillborn. 1966  had the h i g h e s t i n c i d e n c e o f t h e f o u r y e a r s .  When p r o j e c t e d  i n c i d e n c e f o r 1968 which i s e s t i m a t e d t o range between 0.92 and 1.19 p e r 1,000 b i r t h s i s c o n s i d e r e d as w e l l , Two t h i n g s suggest in  the 1966 peak appears  t o be a "normal"  variation.  the 1966 peak i s n o t due to b e t t e r r e g i s t r a t i o n o f cases  t h a t y e a r compared t o t h e o t h e r t h r e e .  The number o f cases o f P o l y d a c t y l y  a s c e r t a i n e d through sources o t h e r than the R e g i s t r y i s n o t n o t a b l y d i f f e r e n t for  the f o u r y e a r s :  and seven cases  f o u r cases  (1967).  (1964), n i n e cases (1965), f i v e cases  (1966)  I n a d d i t i o n t h e r e i s no s t r i k i n g t r e n d f o r the  i n c i d e n c e o f o t h e r anomalies  e s t i m a t e d from R e g i s t r y d a t a t o peak i n 1 9 6 6 .  As can be seen from T a b l e V a s i n g l e form o f P o l y d a c t y l y , u l n a r d u p l i c a t i o n , appears ary  t o be r e s p o n s i b l e f o r the i n c r e a s e d i n c i d e n c e o f supernumer-  d i g i t s i n 1966.  Common f a c t o r s i n t h e h i s t o r i e s o f t h e u l n a r cases have  not been d e t e c t e d .  ^ f i g u r e s on s t i l l b i r t h s i n B.C. from T a b l e s 27 ( 1 9 6 4 , 1965) and 35 ( 1 9 6 6 , 1967) i n t h e 93rd, 94th, 95th and 96th Reports on V i t a l S t a t i s t i c s o f the P r o v i n c e o f B r i t i s h Columbia  25 Table IV.  Incidence of Polydactyly i n B r i t i s h Columbia, 1964 - 1967  1964 probands  1965  1966  1967  Total  30  30  44  34  138  live births*  35,897  33,669  32,502  32,899  134,967  incidence (per 1,000)  0.84  0.89  1.35  1.03  1.02  *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 S p e c i f i c Types of Polydactyly i n 1964 - 1967  Type o f P o l y d a c t y l y  1964  r a d i a l  9  t i b i a l  1  u l n a r  9  f i b u l a r  5  (1 )  3  0?)  u l n a r  &  f i b u l a r  unknown  3  t o t a l  Note:  30  0  1965  )  '  ' #  1966  8  1967  (2)  2  7 1  11 .  (3)  6 3 1  30  (1)  23  (3)  (1 )  2 11  (3)  7  6  (1 )  3  7  (5)  1  (1 )  .2  44  (1 )  34  Number of cases with m u l t i p l e major anomalies i n d i c a t e d 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 s c r u t i n i z e d i n an attempt to  detect c l u s t e r i n g .  Month of b i r t h of the probands i s tabulated i n Table VI.  Comparing, i n d i v i d u a l months, the greatest number of probands were born i n May 1966; however b i r t h s were not p a r t i c u l a r l y frequent i n May f o r other years. Coincident month of b i r t h was the only apparent f a c t o r shared by the probands with birthdays i n May 1966;, the number w i t h a s i m i l a r - t y p e of d u p l i c a t i o n or close proximity of b i r t h p l a c e was not s t r i k i n g . An increased number of probands were born i n May and i n J u l y proportionate to l i v e b i r t h s f o r the province whereas incidence i n January and October was lowest.  Three-month spans 1964 - 1967 show seasonal incidence f o r February-  March-April (0.95), August-September-October (0.98) and November-DecemberJanuary (0.97) approximates the o v e r a l l value of 1.02 i s (1.19) higher.  whereas May-June-July  The s l i g h t l y increased incidence of P o l y d a c t y l y pertains  to i n f a n t s conceived i n August-September-October.  E x c l u s i o n of cases with  m u l t i p l e major anomalies known to,show an increased a s s o c i a t i o n with Polydactyly and exclusion of a l l cases with m u l t i p l e major anomalies give . a s i 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 w i t h Polydactyly does not appear to be a l t e r e d by the i n c l u s i o n of cases with m u l t i p l e congenital anomalies.  D.  Incidence and i i a c i a l o r i g i n R a c i a l o r i g i n of most of the probands i s Caucasian, however there are a  few c h i l d r e n i n the Indian (10) descent.  study known to be of Chinese (2)  or of North American  R a c i a l background of newborns i s d i s t i n g u i s h e d only as  "native Indian" or non-Indian i n v i t a l s t a t i s t i c s f o r the province.  Non-  Indian can be equated with Caucasian without too great an error because there i s no s i z e a b l e population of Negro people i n the province and the l a r g e s t  28 Table VI.  Incidence of Polydactyly i n B r i t i s h Columbia by Month  Number of probands born i n 1964  1965  1966  1967  Incidence* per 1.000 l i v e b i r t h s  January  5  -  1  2  0.73  ( 8)  February  1  6  3  1  1.05  (11)  March  2  4  2  3  0.93  (11)  April  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)  30  30  44  34  total  .  •  138  *figures on l i v e 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 S t a t i s t i c s of the Province of B r i t i s h Columbia  29 non-Caucasian group among n o n - I n d i a n s i s o f O r i e n t a l d e s c e n t ( s e e p. 1 4 ) . S t u d i e s i n d i c a t e P o l y d a c t y l y among Japanese ( N e e l , 1958) and Chinese (Tan, 1969) people has an i n c i d e n c e s i m i l a r t o t h a t o f C a u c a s i a n s ,  consequently the  O r i e n t a l p o p u l a t i o n o f B.C. i s n o t expected t o 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 i n c i d e n c e f i g u r e f o r n o n - I n d i a n s .  I n c l u d i n g probands about whom no  comment was made r e g a r d i n g r a c i a l background i n t h e n o n - I n d i a n group, t h e i n c i d e n c e o f P o l y d a c t y l y i n 1964 - 1967 among l i v e b o r n C a u c a s i a n s o f B.C. was 128 out o f 126,244* o r 1.01 p e r 1,000. I t i s i m p o s s i b l e t o e s t i m a t e t h e e x t e n t t o w h i c h n o n - I n d i a n s have c o n t r i buted t o t h e i n c i d e n c e o f P o l y d a c t y l y among t h e n a t i v e I n d i a n 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 " n a t i v e I n d i a n s " r e s i d i n g w i t h i n t h e p r o v i n c e " r e f e r t o I n d i a n s 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 I n d i a n s l i v i n g on o r o f f r e s e r v e s , and e n f r a n c h i s e d I n d i a n s , some o f whom may be o f mixed ( 9 3 r d Report on V i t a l S t a t i s t i c s o f t h e P r o v i n c e o f B.C., p. M17). parents  descent" Both  o f a t l e a s t t h r e e , and p o s s i b l y four o f t h e probands a r e o f predominantly  Indian descent.  I n a n o t h e r case b o t h p a r e n t s  and i n t h e r e m a i n i n g Indian-Caucasian  descent,  cases o n l y one p a r e n t i s I n d i a n (3) o r one p a r e n t i s  ( 2 ) , and t h e o t h e r p a r e n t  r a c i a l background ( 3 ) .  are of Indian-Caucasian  i s C a u c a s i a n (2) o r o f unknown  Probands appear t o be descended from a t 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 a n o t h e r .  Acknowledging the inherent  l i m i t a t i o n s , t h i s s t u d y found t e n 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 " n a t i v e I n d i a n " i n f a n t s , an i n c i d e n c e o f 1.15 p e r 1,000. I n t h e group o f I n d i a n 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 e i g h t cases and r a d i a l i n two c a s e s .  Among p o s t a x i a l cases a r e t h r e e 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 o f w h i c h have m u l t i p l e c o n g e n i t a l a n o m a l i e s , one proband w i t h u l n a r , and f o u r 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 I n d i a n b i r t h s i n B.C. from Tables 3 (1964, 1965) and 11 (1966, 1967) o f t h e 93rd, 94th, 95th and 96th R e p o r t s on V i t a l S t a t i s t i c s o f t h e P r o v i n c e o f 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 c h i l d r e n i s i n contrast w i t h the f i n d i n g s f o r the t o t a l B.C. population.  Four of the  s i x c h i l d r e n without m u l t i p l e congenital anomalies ( p o s t a x i a l 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  p o s t a x i a l d u p l i c a t i o n has p r i m a r i l y been introduced by non-Indian elements. Furthermore i t s expression could be influenced by modifying f a c t o r s which are c h a r a c t e r i s t i c of the Indian gene pool. D e t a i l e d r a c i a l background i s known f o r one of the two probands with r a d i a l Polydactyly. descent.  In that case the parents are u n l i k e l y to be of mixed  Thus i t can be speculated that d u p l i c a t i o n of the thumb was the  form of P o l y d a c t y l y o r i g i n a l l y most frequent among the Indians. hypothesis i s reasonable  This  considering the theory American Indians are of  mongoloid e x t r a c t i o n (jenness, 1955).  Detection of a hemoglobin v a r i a n t  common to Chinese and to North American Indians (Blackwell et aX, 1963) the theory of a l i n k between the two peoples.  supports  In a d d i t i o n i t i s i n t e r e s t i n g  that f i b u l a r P o l y d a c t y l y was more common than u l n a r i n the predominantly Chinese population studied by Tan (1969).  E.  Incidence by sex The sex of the developing fetus appears to a f f e c t the expression of  Polydactyly as can be seen by the incidence of supernumerary d i g i t s among male and female l i v e b o r n i n f a n t s given i n Table V I I .  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 f u r t h e r c l a s s i f i e d  according to form of d u p l i c a t i o n and sex i n Table XIV. The disproportionate number of a f f e c t e d males i s c h a r a c t e r i s t i c of the anomaly and not l i m i 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 V I I . Incidence of Polydactyly among Males and Females i n B r i t i s h Columbia, 1964 - 1967  1 965  1 96j males probands  females  males  . 1 96r7  1 9616  females  males  females  males  females  19  11  20  10  29  15  27  7  l i v e b o r n i n f a n t s * 18,390  17,507  17,110  16,559  16,625  15,877  16,831  16,068  0.63  1.17  0.60  1.74  0.94  1.60  0.43  incidence  1.03  ^ f i g u r e s 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 ) d i d not demonstrate a large excess of a f f e c t e d males.  Among 30 i n f a n t s with Poly-  d a c t y l y 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 f i n d i n g s f o r the years 1964 and 1965 i n B.C. whereas incidence among males was considerably lower than the B.C. f i g u r e .  33 V.  Parental Age and ParityMaternal age and b i r t h order have been shown to be f a c t o r s i n the  e t i o l o g y of congenital anomalies i n a few instances.  There i s a c o r r e l a t i o n  between i n f a n t s born with a t r i s o m i c chromosomal complement and increased maternal age (Penrose, 1933; McKusick, 1969); McKeown (1961) reported a greater incidence of h a r e l i p w i t h increased maternal age and a r a i s e d incidence of anencephalus among f i r s t - b o r n .  Wright (1926) working w i t h inbred s t r a i n s 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 i n t e r e s t whether maternal age or p a r i t y  among mothers of the probands appears to vary from that of the population of women i n B.C. who d e l i v e r e d i n f a n t s i n 1964 - 1967.  A.  Results and "discussion The mean age of women who d e l i v e r e d l i v e b o r n i n f a n t s i n the t e s t 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. f i g u r e s correspond  These  closely' w i t h mean maternal and paternal ages of the  probands' parents, given i n Table V I I I .  Grouping cases by a f f e c t e d border  o f the limbs, the only ones f o r whom parental age shows much v a r i a t i o n from c o n t r o l f i g u r e s are c h i l d r e n w i t h t i b i a l Polydactyly and c h i l d r e n f o r whom the a f f e c t e d border i s unknown. number of cases.  Both are categories which involve a small  For comparison, i n Kampala the mean maternal age of mothers  of polydactylous i n f a n t s was 23.6 corresponding to a mean f o r 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, w i t h cases grouped according to a f f e c t e d border of the limbs.  In  general, parental age averages s l i g h t l y higher f o r polydactylous female infants  Table V I I I .  Mean Parental Age at the B i r t h of the Probands  Maternal age Border a f f e c t e d  No. of cases averaged*/N  radial  31/31  tibial  5 /  Paternal age Mean  26.1 6  21.8  ulnar  54 / 54  fibular  No. of cases averaged*/N  Mean  32.0  20 /31 6  26.6  26.5  36 / 54  31.3  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  134 /138  26.4  a l l cases a l l B.C.  births**  26.0  3 /  1 /  7  87 /138  53.0 31.0 30.0  *number of cases involved i n c a l c u l a t i n g the mean out of the t o t a l number with that type.of d u p l i c a t i o n * * f i g u r e s on l i v e b i r t h s 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 Male probands cases without m.m.a.*  total no. of cases  Paternal age  Female probands  Male  total no. of cases  cases without m.m.a.  cases without m.m.a.  probands total no. of cases  Female probandscases without m.m.a.  total no. of cases  31.6+ 2.0  —  29.0  —  radial  24.7+ 1/2  25.8+ 1.3  28.0+ 2.4  tibial  22.0  24"r5-  21.5  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  fibular***  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  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  27.0+ 2.3  —  30.4+ 1.8 25.5  32.2+ 1.8  —  32.2  * m u l t i p l e 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 age.  there i s the s u g g e s t i o n  sex r a t i o v a r i e s i n v e r s e l y w i t h i n c r e a s i n g m a t e r n a l  T h i s i s n o t due t o cases a s s o c i a t e d w i t h m u l t i p l e major malformations  s i n c e p a r e n t a l age f o r female probands w i t h m u l t i p l e c o n g e n i t a l anomalies averages' l e s s ( p a t e r n a l , 29.2; m a t e r n a l , 24.8) than f o r male probands m u l t i p l e c o n g e n i t a l anomalies ( p a t e r n a l , 35.8; m a t e r n a l , 29.1). cases w i t h m u l t i p l e major anomalies widens the d i s c r e p a n c y  p a t e r n a l 32.2, m a t e r n a l  Exclusion of  between mean  p a r e n t a l age f o r male and f o r female probands.(male probands: m a t e r n a l 25.1; female probands:  with  p a t e r n a l 29.1,  27.8).  Considering  i n d i v i d u a l types o f d u p l i c a t i o n , the g r e a t e s t d i f f e r e n c e between mean p a r e n t a l age  o f male and o f female probands i s seen among u l n a r cases without m u l t i p l e  major anomalies (P<.01).  W i t h a l a r g e r sample a s i g n i f i c a n t i n c r e a s e i n  p a r e n t a l age might a l s o be demonstrated among females w i t h o t h e r types o f Polydactyly. D i s t r i b u t i o n o f cases w i t h P o l y d a c t y l y a c c o r d i n g age  and t o p a r i t y a l o n g  i n 1964 - 1967.  (Table X) resembles t h a t o f a l l i n f a n t s b o r n i n B.C.  There appears t o be l i t t l e d i f f e r e n c e between b i r t h order o f  female probands compared w i t h male and no r e c o g n i z a b l e or d e c r e a s i n g  t o p a r i t y and maternal  trend of i n c r e a s i n g  sex r a t i o among probands b o r n to women o f h i g h e r p a r i t y . F o r  comparison, i n Kampala i t was noted the mean b i r t h order  of polydactylous  i n f a n t s 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 i n British Columbia, 1964 - 1967  Birth order (no. of cases expressed as a percentage of the total) 1  2  3 . 4  5  6  7  B.C. births* 33.0  25.8  17.3  10.5  5.8  3.1  1 .8  probands**  24.3  22.8  11.8  2.2  3.7  0.7  29.4  8  9  1 .1 2.9.  10-14 0.7 -  '0.8 2.2  15+ 0.1  Total number of cases  134,967 136  *figures on live births i n 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  38 VI. A.  Forms of  Polydactyly  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 b o r d e r s  the hands and and  feet.  P r e a x i a l commonly r e f e r s to the  p o s t a x i a l to the  paper.  t h i r d , f o u r t h and  Sometimes i n a d i s c u s s i o n  d e s i g n a t e d to p e r t a i n to the The This  second, t h i r d and  f i f t h d i g i t s only,  f o u r t h d i g i t s are  c a t i o n of the t h i r d or Usually  first  and  fifth  second d i g i t  o n l y one  polysyndactyly  d i g i t s , but  t h e r e may  be  two  one'accessory f i r s t one  fifth,  described  There was  the  .  lateral  f a c t that  dupli-  that•of  i s p r e s e n t on a limb w i t h one  d i g i t and  are  unusual f o r often  infrequent. be  In  affected,  r a d i a l ) accessory f i r s t  one  fifth,  one  or  fifth  accessory t h i r d  or  or more unusual combinations of p o s t a x i a l  and  (1956') d i s c u s s e d a case p r e s e n t i n g seven fingers  middle, ring, and  d u p l i c a t i o n of the u l n a  a single f i f t h  or  b o r d e r of the hands and/or f e e t .  d u p l i c a t i o n i n c l u d i n g the m e t a t a r s a l of the and  Polydactyly  the p r e a x i a l borders may  a p a t i e n t w i t h e i g h t toes on the  f o u r t h toes,  central digits.  always immediately  disregards  tibial  (or t h r e e ,  Bunnell  thumb w i t h d u p l i c a t e d  radially.  first.  a f f e c t e d ; however r a d i a l d u p l i c a t i o n most  cases w i t h r a d i a l and  preaxial duplication. no  specifically  p r e a x i a l to the  Among p o s t a x i a l cases i t i s not  b o t h the p o s t a x i a l and  f o u r t h d i g i t and  and  i s nearly  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  digits,  and  digits  so used i n t h i s  p o s t a x i a l w i l l be  then r e f e r r e d to as  supernumerary d i g i t  f e e t b o t h to be  Occasionally  terms are  second  fourth.  occurs alone and  but  and  i s u s u a l l y q u i t e a s e p a r a t e anomaly from  b o t h hands and/or f e e t a f f e c t e d . hands and  The  of P o l y d a c t y l y  system emphasizes t h a t P o l y d a c t y l y  or m e d i a l to the  the  fifth.  first  of  toe.  fifth and  left  f i n g e r s f l a n k i n g the  absent r a d i u s . foot:  one  Temtamy (1966b)  b i g toe,  second ( s y n d a c t y l o u s ) ,  index  complete third  and  More b i z a r r e cases w i t h 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 a s s o c i a t i o n 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 d u p l i c a t i o n of the f i b u l a r , t i b i a l , and l e s s 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 f i n g e r or toe which may be somewhat b i f i d d i s t a l l y and syndactyly i s l i m 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 f i n g e r s e x h i b i t an anomalous extent of webbing.  I t i s t h i s type of a s s o c i a t i o n which s h a l l be r e f e r r e d 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. do not include cases with m u l t i p l e congenital anomalies.  These  The type of syndactyly  present i n the 11 cases was not s p e c i f i e d . 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 f a m i l y h i s t o r i e s of syndactyly i n a s s o c i a t i o n with supernumerary d i g i t s r a r e l y involved Polydactyly of the thumb or f i f t h f i n g e r . 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 d u p l i c a t i o n of the  f o u r t h f i n g e r with syndactyly of the accessory, the t h i r d and the f o u r t h fingers.  B^ involved syndactyly of toes four and f i v e , often i n a s s o c i a t i o n  with an accessory f i b u l a r toe.  Temtamy (19660) modified the d e s c r i p t i o n s and  c l a s s i f i e d types A^ and B^ as synpolydactyly.  In a d d i t i o n she (Temtamy)  defined a second type of polydactyly-syndactyly complex, polysyndactyly, i n which both 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 may occur. L i t e r a t u r e regarding forms of Polydactyly and polydactyly-syndactyly i s reviewed i n t h i s s e c t i o n .  Results of the B.C. study and d i s c u s s i o n f o l l o w .  40 B.  Thumb Polydactyly Radial d u p l i c a t i o n can be extremely v a r i a b l e .  that a " d u c k - b i l l " appearance  I t has been suggested  (Haas, 1939) and r a d i a l d e v i a t i o n of the d i s t a l  phalanx (Pott, 1884; De M a r i n i s & Sobbota, 1957) are minor manifestations of polydactylous thumb.  Accessory d i g i t s range from a pedicle or s k i n 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 f u n c t i o n a l b i - or t r i p h a l a n g e a l d i g i t . or consist of two independent rays.  D u p l i c a t i o n may be polysyndactylous  Often there i s some degree of d e v i a t i o n of  the accessory and/or p r i n c i p a l thumb ( M i l l e s i , 1967); o c c a s i o n a l l y the supernumerary d i g i t grows at r i g 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 w i t h the  f i n d i n g s 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 l a r g e r of the two thumbs i s f u n c t i o n a l l y p e r f e c t .  Often  however i t i s rather small i n comparison to the thumb on the opposite hand and may present a v a r i a b l e degree of l a t e r a l r o t a t i o n of the f i r s t metacarpal so that i t l i e s more i n the plane of the f i n g e r s .  In extreme cases n e i t h e r the  p r i n c i p a l or the accessory thumb i s able to oppose the f i n g e r s (Handforth, 1950). Injury to the p r i n c i p a l thumb at the time the accessory i s removed may  contri-  bute to i t s small s i z e , and the degree of d e v i a t i o n present can be compounded as a r e s u l t of surgery (Wassel, 1969). Extent of d u p l i c a t i o n can be c l a s s i f i e d i n the f o l l o w i n g way according to the point at which d i v i s i o n i n t o two rays occurs (Wassel, 1969): d i s t a l phalanx,  (b) duplicated d i s t a l phalanx,  (d) duplicated proximal phalanx, carpal,  (c) b i f i d proximal phalanx,  (e) b i f i d metacarpal,  (g) triphalangism and (h) p e d i c l e .  (a) bifid  ( f ) duplicated meta-  Complete d u p l i c a t i o n of the  proximal phalanx, each w i t h i t s own epiphysis or a common  epiphysis a r t i c u -  41 l a t i n g w i t h 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 s e v e r a l s t u d i e s .  T h i r t y - f o u r out of 79  (43 f ) of the polydactylous thumbs i n a review of 70 cases seen at the Univers i t y of Iowa H o s p i t a l s had t h i s type of d u p l i c a t i o n (Wassel, 1969).  Handforth  (1950) found i n over h a l f of h i s 13 cases the accessory o r i g i n a t e d at the d i s t a l end of the metacarpal (10/16 thumbs), and t h i s 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 f i n d i n g s of the three aforementioned s t u d i e s :  bifid  and duplicated d i s t a l phalanx comprised 16 fo (range: 13-18 fo) of the polydactylous 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 w i t h r a d i a l Polydactyly have d u p l i c a t i o n of the terminal phalanx. Wassel (1969) t a l l i e d t r i p h a l a n g e a l d u p l i c a t i o n separately (15/79 thumbs) whereas t r i p h a l a n g e a l thumbs observed i n the studies of Handforth (1950) and Tan (1969) were included i n the above f i g u r e s .  Triphalangism accounts f o r  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 w i t h 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 " p e d i c l e 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 w i t h the p r i n c i p a l thumb. R a d i a l d u p l i c a t i o n i s more commonly u n i l a t e r a l which can be seen from Table X I . The one study which represents incidence (Tan, 1969) found a r a t i o of approximately three r i g h t [R|] to one l e f t [ l ] f o r u n i l a t e r a l [u] cases.  A  preponderance of cases w i t h the r i g h t side a f f e c t e d has been noted i n other studies', and few i n d i v i d u a l s w i t h b i l a t e r a l [B] r a d i a l Polydactyly.  I t should  42 Table X I . Hand A f f e c t e d i n Cases w i t h R a d i a l P o l y d a c t y l y  Unilateral Reference Farabee  Right  (1903)  Handforth Barsky Temtamy Tan  (1950)  (1958) (19661))  (1969)  Wassel  (1969)  Bilateral  Left  Total  Total  (34).  (28)  (62)*  28  8  3  (16)  11  2  ( 7)  24**  1  5  2  7  18  5  23  2  (12)  ( 2)  61***  9  ^ a f f e c t e d side unknown i n a number of a d d i t i o n a l cases * * a f f e c t e d side unknown i n one case * * * a f f e c t e d side known f o r 14 cases only  43 be pointed out that a disproportionate number of cases w i t h b i l a t e r a l d u p l i c a t i o n have a t r i p h a l a n g e a l thumb(s). Incidence of r a d i a l P o l y d a c t y l y i n Singapore was 25 / 36,427 or 0.69 1,000  l i v e b i r t h s (Tan, 1969).  per  E x c l u s i o n of cases with an accessory t r i p h a l a n -  geal thumb, a form of Polydactyly d i s t i n c t i n several respects from d u p l i c a t i o n i n v o l v i n g a biphalangeal thumb, gives an incidence of 0.66.  Studies i n  conjunction w i t h the World Health Organization (Stevenson et a l . , 1966) s i m i l a r incidence f i g u r e s f o r r a d i a l P o l y d a c t y l y among the Chinese: 0.60  per 1,000; Singapore, 0.50  C.  Hong Kong,  (l/20 mothers was Eurasian); Kuala Lampur, 0.46.  Incidence among Caucasians was considerably lower: B e l f a s t , 0.07  found  Melbourne, 0.13  and  (Stevenson et a l . , 1966).  Triphalangeal f i r s t d i g i t s Triphalangy as a p r e a x i a l anomaly can a f f e c t e i t h e r 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 r a t h e r than the normal two.  I t i s more commonly seen on the hands than on the f e e t and  may  be associated w i t h some degree of b i f i d d u p l i c a t i o n . 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 i n t e r e s t i n g review of cases p r i o r to 1903 was compiled  Farabee (1903) who  by  c i t e d a report by Reider (1900) of a boy whose l e f t thumb  and index f i n g e r had four phalanges each. I t has long been debated whether hyperphalangy of the f i r s t d i g i t r e f l e c t s a hypoplastic process, a d u p l i c a t i o n 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 i n t e r p r e t e d as absence of the true p o l l e x (or h a l l u x ) and d u p l i c a t i o n 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 w i t h a t r i p h a l a n g e a l 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 f o r t h i s hypothesis, or f o r the concept that triphalangy i s a form of hypoplasia.  Haas (1939) believed t h i s l a t t e r view and proposed that the t r i -  phalangeal state r e s u l t e d 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 f i n d i n g however, and some t r i p h a langeal f i r s t rays have been noted to have a s i n g l e proximal epiphysis or d i s t a l epiphysis.  An a l t e r n a t e 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 f a c t that t r i p h a l a n g e a l f i r s t d i g i t s are frequently associated with d u p l i c a t i o n of phalanges or whole rays. Temtamy (19661a), i n order to r e c o n c i l e the opposing views, suggested cases could be d i s t i n g u i s h e d by the presence of a normal or abnormal f i r s t metacarpal. In her scheme, cases with an abnormal metacarpal show no a s s o c i a t i o n with Polydactyly. index f i n g e r .  In a d d i t i o n , she recognized a t h i r d c l a s s :  Polydactyly of the  This included cases which represent the extreme among the  possible v a r i a t i o n s 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 r a d i a l rays are t r i p h a l a n g e a l (Lapidus & G u i d o t t i , 1944).  the  Because i t i s not  c l e a r whether the presence of an abnormal or normal f i r s t metacarpal i s as d i s c r i m i n a t e a f a c t o r as suggested, and due to the controversy over cases included as d u p l i c a t i o n of the second d i g i t , i t seems reasonable to consider the various forms of t r i p h a l a n g e a l f i r s t d i g i t s as v a r i a t i o n s i n morphology which can r e 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 r e l a t e d 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 t r i p h a l a n g e a l thumbs and dactyly/imperforate There are two Brown, 1962). f i n g e r s and  from the o b s e r v a t i o n  imperforate  anus/vertebral  of p a t i e n t s  anus, s t r o n g l y s u g g e s t i v e  with  of the  poly-  anomalies syndrome.  f u n c t i o n a l c a t e g o r i e s o f t r i p h a l a n g e a l thumbs (Swanson &  In type I the t r i p h a l a n g e a l d i g i t s are a b l e to oppose the  other  the supernumerary middle phalanx i s u s u a l l y wedge shaped, r e s u l t i n g  i n u l n a r or r a d i a l d e v i a t i o n of the d i s t a l end more f r e q u e n t l y u n i l a t e r a l and  sporadic.  of the thumb.  In type I I o p p o s i t i o n i s not  f a c t o r y , the t r i p h a l a n g e a l d i g i t b e i n g l o n g and p l a n e as the o t h e r f i n g e r s .  T h i s type i s  o f t e n implanted  satis-  i n the same  T h i s type i s more f r e q u e n t l y b i l a t e r a l w i t h  a  positive family history. Triphalangeal  thumbs, w i t h or without an a s s o c i a t e d degree of  bifid  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 c o n t r a s t w i t h dactylous  biphalangeal  poly-  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 f a m i l y , are more l i k e l y to come to a p h y s i c i a n ' s a t t e n t i o n and Stieve  (1916) and  pared to 90 families.  cases r e p o r t e d An three  o f Swanson and.Brown (1962) l i s t e d 23  cases b i l a t e r a l , The  be r e p o r t e d .  67 out  sex r a t i o i s not  of 81  equal due  bilateral  The  of  cases u n i l a t e r a l com-  cases o c c u r i n g i n 19  to an excess of a f f e c t e d males among  (Swanson & Brown, 1962).  estimate  of f r e q u e n c y was  made by L a p i d u s et a l . (1943) who  cases of t r i p h a l a n g e a l thumbs a s s o c i a t e d w i t h an a c c e s s o r y  75,000 d r a f t e e s , one i n the study by Tan incidence  reviews  w i t h a p o s i t i v e f a m i l y h i s t o r y f o r the (1969) was  1 / 36,427 or 0.03  per  1,000  found  thumb among  trait.  Incidence  newborns.  The  of t r i p h a l a n g e a l thumbs w i t h o u t a s s o c i a t e d 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 w r i t t e n regarding d u p l i c a t i o n of the f i r s t toes.  T i b i a l Polydactyly occurs as a s a l i e n t feature of polysyndactyly, but i t i s unknown i f t h i s s p e c i a l type of P o l y d a c t y l y accounts f o r a considerable p o r t i o n of cases.  pro-  Parabee.(1903) i n h i s massive review noted t i b i a l Poly-  d a c t y l y frequently associated with accessory d i g i t s of the hands.  His data,  extracted from a number of t a b l e s , i s presented i n Table X I I . Although the cases i n Table X I I 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 P o l y d a c t y l y .  In a d d i t i o n 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 d u p l i c a t i o n . Approximately 29 % (13/45) of the cases t a l l i e d by Farabee had p r e a x i a l d u p l i c a t i o n of one or both limbs of the hands and f e e t and 38 % (17/45) had t i b i a l plus ulnar accessory d i g i t s .  approximately  I t i s strange there was  no a s s o c i a t i o n of t i b i a l w i t h f i b u l a r accessory d i g i t s , since most cases with p o s t a x i a l and p r e a x i a l P o l y d a c t y l y may w e l l have been instances of polysyndactyly.  Polysyndactyly w i l l probably a l s o account f o r 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  w i t h accessory t r i p h a l a n g e a l thumbs s i m i l a r to the reports of Hefner (1940) and Manoiloff (1931).  E.  P o l y d a c t y l y of the index f i n g e r . Polydactyly of the index f i n g e r i s reported to vary from a s k i n tag  attached a t the proximal phalanx to some degree of d u p l i c a t i o n 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) f i n g e r ; i n one case syndactyly involved a l l the fingers(Cohn, 1932).  I t may not be c l e a r whether an anomalous  r a d i a l d i g i t ( s ) represents a t r i p h a l a n g e a l thumb or d u p l i c a t i o n of the index  47 Table X I I .  Frequency of Accessory D i g i t s i n Conjunction with T i b i a l Polydactyly  A f f e c t e d border  Wo.  of cases  t i b i a l d u p l i c a t i o n only R L B  tibial tibial tibial  1 4 4  t i b i a l and r a d i a l d u p l i c a t i o n R L B B B  tibial, tibial, tibial, tibial, tibial,  L radial B radial L rradial R radial B radial  1 3 1 1 3  t i b i a l , r a d i a l and ulnar d u p l i c a t i o n B  tibial,  B  radial,  B  ulnar  4  t i b i a l and ulnar d u p l i c a t i o n L R B B  tibial, tibial, tibial, tibial,  B B R B  ulnar ulnar ulnar ulnar  t i b i a l d u p l i c a t i o n , no other ?  2 5 1 5 details  tibial  .18 total  Source:  Farabee (1903)  63  48 f i n g e r with absence of the thumb.  Temtamy (1966b) suggests the l a t t e r cases  may be d i s t i n g u i s h e d by morphology and dermatoglyphics.  D u p l i c a t i o n of the  index f i n g e r i s the type of Polydactyly reported to be l e a s t 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 f i n g e r (Wood, 1970).  F..  Polydactyly of the third, or f o u r t h f i n g e r s D u p l i c a t i o n of the t h i r d or f o u r t h f i n g e r may be i n the form of a  syndactylous accessory d i g i t (proband number 123) 1908;  Kanavel, 1932;  B e l l , 1953).  or polysyndactylous  non(Mathew,  Polydactyly of the f i f t h f i n g e r s and toes  has been noted i n some i n d i v i d u a l s with an independent accessory t h i r d or. fourth finger.  The polysyndactylous  form described as synpolydactyly  Temtamy (l966b ) appears to be discussedmmost often i n the l i t e r a t u r e .  by This  x  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 d u p l i c a t i o n v a r i e s but i s always  syndactylous.  T y p i c a l features of t h i s type of Polydactyly were presented-by a case  (PLH)  brought to the a t t e n t i o n of the i n v e s t i g a t o r but not included as a proband. The c h i l d had supernumerary proximal and medial phalanges of the f o u r t h f i n g e r b i l a t e r a l l y without d u p l i c a t i o n 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 f o u r t h f i n g e r s .  The  mother and maternal grandmother of PLH had b i l a t e r a l syndactyly of f i n g e r s three and four; however i t i s not known i f duplicated elements of the f o u r t h f i n g e r were included i n the web.  A f a m i l i a l h i s t o r y of the t r a i t i s common.  Occasionally with synpolydactyly  the f o u r t h and f i f t h f i n g e r s are syndactylous  or there may be an a s s o c i a t i o n with accessory toes polysyndactylous f o u r t h and f i f t h d i g i t s ( B e l l , 1953;  Temtamy, 1966b),  to the  49  G.  Ulnar P o l y d a c t y l y Supernumerary d i g i t s of the u l n a r border only are n e a r l y always rudimen-  tary.  These may consist of a w a r t - l i k e p r o j e c t i o n , a f l e s h y s k i n tag or most  often a p e d i c l e which contains c a r t i l a g i n o u s of o s s i f i e d phalangeal elements. B i l a t e r a l pedicles w i t h 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 ( 1 9 6 1 ) . Frequently there i s a f i n g e r n a i l .  Attachment i s  u s u a l l y by a narrow s t a l k of s k i n to the l a t e r a l border of the proximal phalanx of the f i f t h f i n g e r or the area near the head of the f i f t h metacarpal.  The  occurrence of a supernumerary d i g i t o f f the r a d i a l aspect of the f i f t h f i n g e r 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 a t t a c h -  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 f i n g e r 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 w i t h 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 u l n a r d i g i t s , g i v i n g meticulous a t t e n t i o n to t h e i r morphology.  He c l a s s i f i e d supernumerary f i f t h f i n g e r s  p r i m a r i l y by the degree of proximal c o n s t r i c t i o n , p o i n t i n g out however i n a c t u a l i t y there i s a gradation from the most poorly d i f f e r e n t i a t e d appendage suspended by a thread of s k i n to the p e r f e c t l y formed, f u n c t i o n a l f i n g e r .  It  was stressed that most accessory u l n a r d i g i t s are small with signs of i n h i b i t e d 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 r e f e r r e d to as postminimi.  I t was noted c a r t i l a g e never extended i n t o the basal region of  the postminimus,  a s i n g l e small phalanx was often present, and bone formation  was retarded or nonexistant.  Cummins assumed that the s t a l k was the region  where growth was most i n h i b i t e d , and with the r e s t of the d i g i t growing more r a p i d l y , a p e d i c l e formed. Danforth (1919) suggested that- e a r l y i n development an accessory u l n a r d i g i t was s i m i l a r to the other f i n g e r s .  However i n most cases d i f f e r e n t i a t i o n  did not proceed synchronously with the other d i g i t s and the accessory tended to become c o n s t r i c t e d o f f .  I t was postulated that i n c e r t a i n cases spontaneous  amputation or sloughing o f f of pedunculated postminimi occurred ( s t r e e t e r , 1930). At b i r t h a l l that remains of the accessory d i g i t i s a "pointed s t a l k " or "nodular e l e v a t i o n " 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 i n t e r p r e t e d to be i n d i c a t i v e of spontaneous amputation.  Cummins f u r t h e r speculated that amputation might occur  s u f f i c i e n t l y e a r l y i n the development of the fetus that a l l evidence of the . s i t e of attachment be o b l i t e r a t e d due to reorganization and growth. Simpkiss and Lowe (1961) found 2U i n f a n t s with supernumerary d i g i t s of the ulnar border only (H1 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, 1  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 s i n g l e 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 s k i n alone and i n each case to the proximal phalanx of the f i f t h f i n g e r . An a d d i t i o n a l case had ulnar and f i b u l a r Polydactyly.  unilateral  From the data of Farabee (1903) i n Table X I I I  i t can be seen that f i b u l a r Polydactyly i s more commonly seen i n a s s o c i a t i o n w i t h ulnar accessory d i g i t s than t i b i a l or r a d i a l .  H.  F i b u l a r 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 pedicle.  accessory d i g i t , or l e s s frequently a  The accessory toe i s u s u a l l y 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 d u p l i c a t i o n of the f o u r t h rather than the f i f t h d i g i t as an accessory  metatarsal  element may show an equal or greater a s s o c i a t i o n with the f o u r t h metatarsal. Less frequently there i s d u p l i c a t i o n of the t h i r d toe (proband number 110).  51 Table XIII.  Frequency of Accessory D i g i t s i n Conjunction with Ulnar Polydactyly  Affected border  EFo. of cases  u l n a r d u p l i c a t i o n only R L B  15 13 93  ulnar ulnar ulnar  ulnar and f i b u l a r d u p l i c a t i o n L L L R B B  ulnar, ulnar, ulnar, ulnar, ulnar, ulnar,  L R B R R B  fibular fibular fibular fibular fibular fibular  1 3 4 5 8 93  ulnar and t i b i a l d u p l i c a t i o n ?  ulnar,  ?  13  tibial  ulnar and r a d i a l d u p l i c a t i o n B  ulnar,  B radial  7  u l n a r , r a d i a l and t i b i a l d u p l i c a t i o n B  ulnar,  R  radial,  B  4  tibial  ulnar d u p l i c a t i o n , no other d e t a i l s ?  231  ulnar total  Source:  Farabee (1903)  490  52  An accessory f i b u l a r d i g i t syndactylous to the f o u r t h and f i f t h toes has been considered a d i s t i n c t anomaly, synpolydactyly, which may associate w i t h polysyndactylous d u p l i c a t i o n of the t h i r d f i n g e r ( B e l l , 1953;  Temtamy, 1966b).  In  f a m i l i e s w i t h f i b u l a r synpolydactyly, d u p l i c a t i o n does not occur i n i n d i v i d u a l s w i t h nonsyndactylous f o u r t h 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  f i n d i n g s suggest d u p l i c a t i o n i s more commonly u n i l a t e r a l among cases w i t h 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 P o l y d a c t y l y w i t h syndactyly of f i n g e r s three and four ( l e f t ) .  This  was  most l i k e l y associated w i t h b i l a t e r a l f i b u l a r P o l y d a c t y l y (? synpolydactyly) since Farabee found among u l n a r - f i b u l a r cases 97 w i t h 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 d u p l i c a t i o n . F i b u l a r accessory d i g i t s commonly occur w i t h u l n a r d u p l i c a t i o n but r a r e l y with t i b i a l or r a d i a l d u p l i c a t i o n . Egawa e t . a l . (1969) included d e s c r i p t i v e d e t a i l s and photographs of the forms of d u p l i c a t i o n 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 w i t h b i l a t e r a l d u p l i c a t i o n of the d i s t a l phalanx, f o u r t h toes.  Syndactyly joined the accessory to the f i f t h toes (13),  to the f o u r t h toes ( l ) , and i n at l e a s t two cases involved the f o u r t h , f i f t h and supernumerary d i g i t s (? synpolydactyly). independent accessory toes.  In only two cases were there  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 P o l y d a c t y l y 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 r e f e r r e d f o r assessment and c o r r e c t i v e 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  p o s t a x i a l supernumerary toes, p a r t i c u l a r l y p e d i c l e s , 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 P o l y d a c t y l y among Japanese people. support t h i s as w e l l (see p.  I.  form of fibular  Findings of Neel (1958) would appear to  39).  U l n a r - f i b u l a r Polydactyly The presence of ulnar and f i b u l a r d u p l i c a t i o n has often been noted i n the  same i n d i v i d u a l , but has not p r e v i o u s l y been considered a d i s t i n c t form of p o s t a x i a l Polydactyly.  In t h i s 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 r e f e r r e d to as u l n a r - f i b u l a r Polydactyly. I n d i v i d u a l s with both ulnar and f i b u l a r d u p l i c a t i o n and i n d i v i d u a l s with ulnar (or f i b u l a r ) accessory d i g i t s who have a f a m i l y h i s t o r y of f i b u l a r (or ulnar) d u p l i c a t i o n 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 v a r i a b l e . C h a r a c t e r i s t i c a l l y polydactylous f e e t present well-formed  accessory  toes whereas accessory ulnar d i g i t s range from very rudimentary to formed.  fifth fully-  Children of parents with u l n a r - f i b u l a r d u p l i c a t i o n 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 c h i l d r e n with ulnar and/or f i b u l a r accessory d i g i t s .  I t seems h i g h l y u n l i k e l y a f a m i l y with  s e v e r a l a f f e c t e d i n d i v i d u a l s 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 d i g i t s and the pattern of inheritance s e c t i o n and the s e c t i o n on g e n e t i c s ) .  accessory  (see r e s u l t s and d i s c u s s i o n i n t h i s  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 i n t e r e s t because a f f e c t e d i n d i v i d u a l s i n some f a m i l i e s have p o s t a x i a l i n a d d i t i o n to p r e a x i a l supernumerary d i g i t s . P r e a x i a l malformation i s probably always present whereas expression of p o s t a x i a l components i s more v a r i a b l e . hands.  The f e e t are more severely a f f e c t e d than the  P a r t i a l or complete d u p l i c a t i o n 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 ) d e v i a t i o n to a h a l l u x varus deformity. three to the greatest extent.  A l l the toes are syndactylous with toes two  and  Sometimes a supernumerary f i b u l a r toe i s present  as w e l l , u s u a l l y i n the form of a p e d i c l e 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 ( r a d i a l ) d e v i a t i o n of the d i s t a l phalanx.  Fingers three and four are syndactylous  to  a v a r i a b l e extent, and i n some cases there i s a pedicle-type accessory ulnar digit.  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.  D u p l i c a t i o n of f i n g e r s (88/137*, 64 fo) occurs more frequently  than d u p l i c a t i o n of toes (33/137, 24 f ) or f i n g e r s and toes (16/137, 12 fo). Most cases (135) have a s i n g l e supernumerary d i g i t per limb; two have seven d i g i t s on one limb.  exceptions  D u p l i c a t i o n 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-  d a c t y l y (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 d e s c r i p t i o n of supernumerary d i g i t ( s ) was unavailable f o r one case  55  Table XIV. S i t e of D u p l i c a t i o n According to Sex of the Probands Preaxial S i t e of d u p l i c a t i o n  Postaxial  males  females  L hand  9  3  12  14  23  R hand  12  '5 "  17  5  5  2  18  26  B hands  1  total  1*  L foot R foot  . 2  2  B feet  2  4  males  females  total  7  2  9  2  6  8 6  L**& R f e e t  1  R hand, R foot B hands, B feet  7  B hands, L foot  1  1  1  3  10  1  B hands, R foot  1  1  R**& L hands, R foot  1  1  L hand, B f e e t  1  R hand, B f e e t  1  Border Unknown L hand  1  1  R hand  •1  1  B hands  1  R foot  1  1  B feet  2  2  unknown  1  1  * t r i p h a l a n g e a l supernumerary thumb R; t r i p h a l a n g e a l 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 p r e a x i a l (37) or p o s t a x i a l (94) on the hands and/or f e e t ; i n seven cases the a f f e c t e d border i s unknown.  None of the  probands have both 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 , however one s i b (family number 85) has t i b i a l and ulnar Polydactyly and more d i s t a n t 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 ( f a m i l i e s numbers 84, 85, 115) and thumbs ( f a m i l i e s numbers 86, p o s s i b l y 85 and 88).  S i t e of d u p l i c a t i o n according to sex i s also given i n Table XIV.'  The o v e r a l l f i g u r e s of 63 males to 31 females f o r p o s t a x i a l d u p l i c a t i o n and 26 males to 11 females f o r p r e a x i a l d u p l i c a t i o n 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 d u p l i c a t i o n (46 p o s t a x i a l : 31 p r e a x i a l : 3 unknown) accounts for approximately 50 % (46/94) of the p o s t a x i a l cases compared to 84 % (31/37) of the p r e a x i a l cases. Polydactyly  Most of the u n i l a t e r a l p r e a x i a l cases involve thumb  (29/31, 94 ft), while d u p l i c a t i o n of the f i f t h f i n g e r a f f e c t s 61 %  of the p o s t a x i a l 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 s i m i l a r f o r 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 p r e a x i a l cases there are s l i g h t l y more with r i g h t d u p l i c a t i o n (17 R, 12 L) whereas among u n i l a t e r a l ulnar cases there are few with the r i g h t side a f f e c t e d (23 L, 5 R). These f i v e are males; the only female with r i g h t ulnar Polydactyly has r i g h t f i b u l a r d u p l i c a t i o n as w e l l . Among u n i l a t e r a l cases of the p r e a x i a l and of the p o s t a x i a l borders, tibial d u p l i c a t i o n i s infrequent (17/46).  (2/31) i n contrast to d u p l i c a t i o n e x c l u s i v e l y f i b u l a r  The number of f i b u l a r cases according to sex with r i g h t d u p l i c a t i o n  (2 males : 6 females) i s roughly the opposite of the number with l e f t d u p l i c a t i o n (7 males : 2 females).  This f i n d i n g becomes even more pronounced when  cases with both ulnar and f i b u l a r Polydactyly are also considered. 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).  Pour cases Including  these makes a t o t a l of two males and nine females with r i g h t d u p l i c a t i o n and  eight males and two females' with l e f t d u p l i c a t i o n .  This tendency f o r females  to present r i 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 p r e a x i a l : A3 p o s t a x i a l : 3 unknown) i s l e s s frequent among the probands than u n i l a t e r a l .  P r e a x i a l cases are r a d i a l (1  male, 1 female), one with a supernumerary t r i p h a l a n g e a l thumb r i g h t and a s i n g l e t r i p h a l a n g e a l thumb l e f t , or t i b i a l (2 males, 2 females). have both r a d i a l and t i b i a l d u p l i c a t i o n .  No cases  B i l a t e r a l p o s t a x i a l Polydactyly i s  more commonly ulnar (26) than f i b u l a r (7) or u l 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 u l n a r f i b u l a r Polydactyly. males.  The seven cases with b i l a t e r a l f i b u l a r d u p l i c a t i o n are  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 u l n a r 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 a d d i t i o n both cases of b i l a t e r a l Polydactyly of the f e e t , border  unknown, are males. Table XV describes the forms of d u p l i c a t i o n observed i n the probands. Rudimentary d i g i t s recorded i n medical records as s k i n tags or p e d i c l e s , or noted to have been t i e d off. have a l l been categorized as pedicles i n t h i s table.  Further d e s c r i p t i o n when a v a i l a b l e i s given i n Appendix A.  P r e a x i a l d u p l i c a t i o n tends to c o n s i s t of some degree of b i f i d i t y of the normal bony elements (19), often w i t h 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 c h a r a c t e r i s t i c than a p e d i c l e or s k i n t a g l o o s e l y 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 p e d i c l e s , 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 a v a i l a b l e on three of the cases classed as p e d i c l e s , 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.  D e s c r i p t i o n of the Forms- of D u p l i c a t i o n Presented by the Probands Number of cases  t i b i a l duplication  R  d u p l i c . d i s t a l phalanx d u p l i c . proximal and d i s t a l phalanges extent of d u p l i c . unknown  1 1  L -  -  2  B  Total  1  1 3 2  1  6  total  radial duplication pedicle d u p l i c . d i s t a l phalanx b i f i d proximal phal. and d u p l i c . d i s t a l phalanx d u p l i c . proximal and d i s t a l phalanges p a r t i a l d u p l i c . metacarpal, prox. and d i s t a l phal. p a r t i a l d u p l i c . metacarpal with one d u p l i c . phal. triphalangeal d i g i t extent of d u p l i c . unknown  2 4  5 3  4 1 2 1 3  1 2  1*  7 7 1 4 2 2 3 5  total  ulnar d u p l i c a t i o n  31  pedicle or s k i n tag b e t t e r 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 d u p l i c . unknown  20 1 2 3  1 4  41 1 3 9  total  fibular duplication  54  pedicle well-formed d i g i t R, pedicle L d i g i t syndactylous with 5th 1(57) or 4th ( 1 ) : l a t e r a l to 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 ) well-formed d i g i t l a t e r a l to 5th B; 7th d i g i t i n s e r t e d between toes 3 - 4 L total ulnar-fibular duplication  3  2 3  1 2  2 1 8  6 -  3  3  12 1  p e d i c l e s : B or U ulnar and B or U f i b u l a r at l e a s t one well-formed d i g i t d i g i t l a t e r a l to 5th f i n g e r B; 7th f i n g e r • i n s e r t e d 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 B fibular extent of d u p l i c . unknown .. total border unknown  -  -  4 -  3 4 1  -  -  -  6  -  -  -  2  hand foot Polydactyly  24  '  1 total  ^ t r i p h a l a n g e a l supernumerary thumb R; t r i p h a l a n g e a l thumb L  -  1  1 -  1 2 -  3 3 1  16  7  59' seven cases categorized as p e d i c l e s , 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 f a c t that r a d i a l d u p l i c a t i o n (31 ) occurs more frequently than t i b i a l (6). In a d d i t i o n i t should be noted that among cases with p e d i c l e P o l y d a c t y l y the l e f t side i s more commonly a f f e c t e d (5/7), whereas the more complete forms of prea x i a l d u p l i c a t i o n occur most often on the r i g h t side ( 9 / l l ) . Three cases of polydactylous thumb involve a supernumerary t r i p h a l a n g e a l 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 d u p l i c a t i o n . D u p l i c a t i o n c o n s i s t i n g of a t r i p h a l a n g e a l and/or supernumerary t r i p h a l a n g e a l thumb i s more commonly b i l a t e r a l (2U, 1B) than i s d u p l i c a t i o n i n v o l v i n g a u n i or biphalangeal thumb (22U, 1 B ) . Such a statement may be true only of r a d i a l P o l y d a c t y l y r a t h e r than, p r e a x i a l P o l y d a c t y l y i n general.  Among the probands .  d u p l i c a t i o n of the f i r s t toe i s more frequently b i l a t e r a l (4/6). of t i b i a l P o l y d a c t y l y have f a i r l y  Three cases  complete d u p l i c a t i o n and a l l three are males.  A tendency f o r males to present a greater degree of d u p l i c a t i o n i s not seen w i t h r a d i a l P o l y d a c t y l y where there appears to be no d i f f e r e n c e i n extent of d u p l i c a t i o n according to sex of the proband. Ulnar P o l y d a c t y l y (54) most often takes the form of s k i n 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 i n f r e q u e n t l y on the r i g h t (3). These pedicles u s u a l l y a r i s e from the l a t e r a l side of the f i f t h f i n g e r 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. fingernails.  Some extra d i g i t s have  Descriptions seldom mention the presence of bony t i s s u e (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 f i n g e r s (10) which may a r t i c u l a t e (5/10) are  seen more often i n conjunction w i t h f i b u l a r P o l y d a c t y l y .  60 P o s t a x i a l supernumerary toes tend to be f a i r l y w e l l formed (21 / 24) and i n only three cases are the extra d i g i t s described as p e d i c l e s .  One of these  cases has a well-formed supernumerary toe on the l e f t and a pedicle on the right foot.  I n 15 cases the extra d i g i t appears as a d u p l i c a t i o n of the f i f t h  toe s i t u a t e d 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 r i g h t and medial on the l e f t .  I f the f i f t h and supernumerary are equally  w e l l formed i t may be d i f f i c u l t to decide which i s accessory. In a d d i t i o n a l cases accessory toes i n s e r t e d between the f o u r t h and f i f t h show a p a r t i a l attachment to both the f o u r t h and f i f t h d i g i t s ( l ) . or are more c l o s e l y associated with the f o u r t h ( i i ) , which may represent an excess of m a t e r i a l p e r t a i n i n g to anlagen of the normal f o u r t h d i g i t .  I n s e r t i o n between  the t h i r d and f o u r t h toes occurs as w e l l ( l ) . The proband w i t h t h i s d u p l i c a 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. I n s e r t i o n of a supernumerary ray between d i g i t s three and four may be common when there are two accessory p o s t a x i a l d i g i t s on a limb, f o r t h i s pattern of d u p l i c a t i o n i s also present i n a case of u l n a r - f i b u l a r Polydactyly which has two p o s t a x i a l accessory f i n g e r s on the r i g h t hand. Syndactyly of the supernumerary with the f o u r t h toe (1) or with the  fifth  toe ( 4 ) , or of the supernumerary, f o u r t h and f i f t h toes (3) i s f a i r l y common (8/24).  I t should also be noted that i n cases with e x c l u s i v e l y 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 i n s e r t e d between the f o u r t h and f i f t h or the t h i r d and f o u r t h metatarsals. there i s f u s i o n of extra metatarsal  Among cases with u l n a r - f i b u l a r Polydactyly 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 l e a s t one case.  This f i n d i n g may be of l i m i t e d  s i g n i f i c a n c e and r e s u l t from inadequate d e s c r i p t i o n s .  For at l e a s t 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 d e 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, f i b u l a r duplication among males tends to be l e f t or b i l a t e r a l whereas females tend to have r i g h t Polydactyly.  The extra toe of  over h a l f of the females ( 5 / 8 ) i s immediately medial to the f i f t h , which i s f i v e of the s i x u n i l a t e r a l cases described with this form of duplication. Cases with u l n a r - f i b u l a r Polydactyly tend to have more complete forms of duplication.  Supernumerary d i g i t s limited to pedicle forms are described i n  only three cases; i n others(11) there i s at least one well-formed extra fingers or toes.  (2/ll)  or more  (9/ll)  Fingers are more rudimentary i n f i v e cases  toes i n one. Extra toes are located medial to the f i f t h (1 male, 1 female) and l a t e r a l (2 males).  Fibular polysyndactylous accessory d i g i t s appear to be  more c h a r a c t e r i s t i c of Polydactyly a f f e c t i n g the feet alone, f o r 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 u l n a r - f i b u l a r Polydactyly tend to have somewhat rudimentary extra d i g i t s on one or more limbs. In c a l c u l a t i n g 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 f i b u l a r Polydactyly have been included among cases with u l n a r - f i b u l a r 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 i d e n t i c a l :  compared to 1.02 (B.C.). outlined i n Table XVII.  1.15 (Singapore.)  The types of duplication found by Tan are b r i e f l y As observed i n B.C., duplication of fingers i s more  common (67 $>'-. 64 i° B.C.) than duplication of toes (26 fo : 24 % B.C.) or finge  62  T a b l e XVI.  I n c i d e n c e o f S p e c i f i c Types o f P o l y d a c t y l y i n B r i t i s h  Cases w i t h o u t m u l t i p l e major anomalies  Ho. o f cases  radial duplication . biphalangeal triphalangeal t i b i a l duplication  I n c i d e n c e p e r 1,000 liveborn infants  24 3  0.18 0.02  6  0.04  preaxial duplication  Columbia  0.24  ulnar duplication*  43  0.32  fibular duplication**  20)  0.15  ulnar-fibular duplication  12  0.08  postaxial duplication  0.55  polysyndactyly  1  0.01  s i t e o f d u p l i c a t i o n unknown  5  0.04  114  0.84  24  .0.18  138  1.02  cases w i t h o u t m u l t i p l e major anomalies  Cases w i t h m u l t i p l e major anomalies all  types o f d u p l i c a t i o n  total  *case number 86 i n c l u d e d among u l n a r - f i b u l a r cases * * c a s e s numbers 93 and 110 i n c l u d e d a m o n g • u l n a r - f i b u l a r cases  63  T a b l e XVII.  Types  of P o l y d a c t y l y Pound i n Singapore  Preaxial Site  Postaxial  R  L  18  5  1  1  28  feet  3  -  2  5  11  hands & f e e t  B ulnar, B fibular, L r a d i a l B ulnar, B f i b u l a r  hands  I  R  B  Total  total  Note:  I n c i d e n c e of P o l y d a c t y l y per 1 ,000 was 42/36,427 or 1 . 1 p.  Source:-  Tan,  1969  1 2  42  livebirths  64  and toes (l fo : 12 $ B. C.). the Singapore and the B.C.  However there i s a s t r i k i n g d i f f e r e n c e between  populations regarding,affected border of the limbs.  The frequency of p r e a x i a l d u p l i c a t i o n i n the Singapore population (68 fo) i s n e a r l y equal to the frequency of p o s t a x i a l d u p l i c a t i o n i n B.C.  (71 i°) •  .Among cases w i t h polydactylous hands Tan found r a d i a l d u p l i c a t i o n (90 % : 38 fo B.C.)  more frequent than u l n a r .  P o l y d a c t y l y of the thumb was most often  u n i l a t e r a l ( 2 3 / 2 5 ) , a greater proportion w i t h r i g h t d u p l i c a t i o n (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 w i t h the f i r s t metacarpal (8) n e a r l y as great as that w i t h b i f i d proximal (3) phalanges (4) langeal.  and pedicles ( 6 ) .  and b i f i d  was  or duplicated d i s t a l  In one case the duplicated thumb was  tripha-  P o l y d a c t y l y on the r a d i a l border tended to be a more complete form  of d u p l i c a t i o n 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 u l n a r d u p l i c a t i o n (3/28) i n Tan's study i s  f u r t h e r exaggerated by the f a c t that i n one case the Polydactyly can be a t t r i b u t e d to i n h e r i t a n c e 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 (1.7  : 1).  : l ) . i s increased to a greater extent than that of t i b i a l  D u p l i c a t i o n 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 w i t h 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  F i n d i n g the r i g h t side a f f e c t e d i n these cases strengthens gained from the B.C. and r a d i a l  %)  the  R).  impression  study that r i g h t d u p l i c a t i o n i s more common on the  tibial  borders.  Tan found the l e f t side more f r e q u e n t l y a f f e c t e d among cases w i t h f i b u l a r Polydactyly (5/8).  Pedicles (3) were seen as w e l l 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 d u p l i c a t i o n and females r i g h t as found i n B.C. One a d d i t i o n a l t h i n g to note from the Singapore study i s the presence of thumb P o l y d a c t y l y (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 P o l y d a c t y l y 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 i n f a n t s had a rudimentary accessory ulnar d i g i t (11 U, 1 6 B ) 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 i n f a n t s (90 fo) contrasts with the B.C. f i n d i n g s (39 %) those of Tan  and  (if).  Regarding P o l y d a c t y l y of the f o o t , f i n d i n g s i n the B.C. study can.be compared w i t h 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 w e l l as females, the r i g h t foot was more  commonly a f f e c t e d (Egawa, 1971) whereas the majority of r i g h t u n i l a t e r a l i n the B.C. study are females.  cases  66 VII. A.  Genetics Introduction A number of hypotheses regarding the nature and e t i o l o g y 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).  A h l f e l d (1880) believed Polydactyly r e s u l t e d from i n t r a -  uterine i n j u r i e s .  The r o l e of environmental agents i n the e t i o l o g y 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 i n f a n t s with a h i s t o r y of maternal i n g e s t i o n of thalidomide around day 34 a f t e r the l a s t menstrual period; t r i p h a l a n g e a l thumbs were associated with i n g e s t i o n around day 48 to 50.  In thalidomide pathogenesis accessory  d i g i t s were always p r e a x i a l and d u p l i c a t i o n of f i r s t toes more common than duplicated thumbs.  A syndrome of 'diabetic embryopathy" has also been described  i n which a p l a s i a or hypoplasia of the femurs, cardiac and r e n a l  malformations,  Polydactyly of the f e e t , and abnormalities of the coccyx occur (Kucera et a l . , 1965). Weismann (1893) postulated that Polydactyly r e s u l t e d 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 a t t e n t i o n i n the past; and dominant, recessive and polygenic modes of inheritance have- been, suggested f o r various types and forms of d u p l i c a t i o n . A review of these hypotheses i s given i n t h i s s e c t i o n . 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 are considered separately since with the exception of polysyndactyly they are generally thought to r e s u l t from d i f f e r e n t gene mutations, ftieir simultaneous occurrence c o i n c i d e n t a l (Sverdrup, Gates, 1946;  Temtamy, 1966b.i; Woolf & Woolf,- 1970%  t i o n f o l l o w presentation of the r e s u l t s of the B.C.  Discussion and study.  1922; specula-  67 B.  L i t e r a t u r e 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 a f f e c t e d 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 i n d i v i d u a l s were polydactylous include the reports of Megasthenes who  described an eight-toed race of men  ( P l i n y , c i t e d by B e l l ,  1930), Lucker (1924) who recorded Polydactyly and h a r e l i p 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. 1904)  may  Several references  (Boinet, 1898;  Devay, 1863;  Ballowitz,  r e f e r to the same i s o l a t e d v i l l a g e in'the Departement d'Isere, noted  to have many polydactylous i n d i v i d u a l s with s i x d i g i t s on a limb.  The  trait  was a t t r i b u t e d to intermarriage and i s s a i d to have disappeared when marriages to normal i n d i v i d u a l s became common.  This would be incompatible w i t h dominant  i n h e r i t a n c e (Odrione, 1943), was i n e x p l i c a b l e , and some w r i t e r s proclaimed i t a hoax.  However Daisy Bates (1966) r e l a t e d a s i m i l a r s t o r y regarding a group  of A u s t r a l i a n aborigines.  And the f a m i l y from Bukowina reported by Shevkenek  and Thompson (1933) tends to f u r t h e r support the v a l i d i t y of such accounts. In the k i n s h i p of Shevkenek and Thompson (1933) i t was P o l y d a c t y l y was i n h e r i t e d as a simple autosomal r e c e s s i v e .  concluded postaxial Recessive  inheri-  tance was postulated f o r the Negro f a m i l y i n v e s t i g a t e d by Snyder (1929), and i t i s i n t e r e s t i n g to note that a l l ten o f f s p r i n g (5 males., 5 females) from the marriage of two polydactylous i n d i v i d u a l s were a f f e c t e d .  In a d d i t i o n , pedigrees  of B e l l (1930), Salzano (1961 ) and Mohan (1969) are also compatible with a recessive mode of i n h e r i t a n c e .  P o l y d a c t y l y appeared to be a recessive  character i n the s i b s reported by O l i v e r (1940) but was associated with mental d e f i c i e n c y and p h y s i c a l weakness. a recessive syndrome.  These cases are considered to represent  Other recessive syndromes w i t h a high incidence of  68  p o s t a x i a l P o l y d a c t y l y are Laurence-Moon-Biedl syndrome (see p.118) and  Ellis-  van Creveld syndrome (Smith, 1 970). Gates (1946) accepted the existence of recessive P o l y d a c t y l y ( p o s t a x i a l ) , considered i t very rare i n comparison w i t h the dominant form, and f e l t i t was expressed by a m i l d extent of d u p l i c a t i o n . He points out however that a dominant character with low penetrance would be i n d i s t i n g u i s h a b l e from a recessive.  The World Health Organization study (Stevenson et a l . , 1966)  found no  increased frequency of consanguinity among the parents of polydactylous c h i l d r e n which suggests recessive inheritance accounts f o r a l i m i t e d percentage, i f any, of the cases of Polydactyly unassociated w i t h m u l t i p l e congenital anomalies. The term i r r e g u l a r dominant inheritance was used to e x p l a i n instances where an i n d i v i d u a l assumed to have transmitted P o l y d a c t y l y f a i l e d to express i t (Brandeis, 1915).  There are many examples of t h i s i n f a m i l y h i s t o r i e s of  p o s t a x i a l P o l y d a c t y l y (Sedgwick, 1863; 1937;  Caiman, 1942;  Odrione, 1943;  1969;' Woolf & Woolf, 1970).  Brandeis, 1915;  B e l l , 1930;  P i p k i n & P i p k i n , 1946;  Jackson,  Walker, 1961;  Gates (1946) f e l t i r r e g u l a r dominance was  Mohan, a  simpler explanation f o r the k i n s h i p reported by Snyder (1929) than recessive inheritance.  The e l u s i v e nature of i r r e g u l a r dominance i s i n contrast w i t h 1814;  pedigrees e x h i b i t i n g more conventional dominant inheritance ( C a r l i s l e , Sverdrup, 1922;  Dehus & Snyder, 1932;  De M a r i n i s & Sobbota, 1957;  Barrer, 1947;  Woolf & Woolf, 1970).  Johnston & Davis,  1953;  The f a m i l y reported by  De Marinis & Sobbota (1957) i s of s p e c i a l note due to the f a c t that both parents had b i l a t e r a l ulnar and f i b u l a r P o l y d a c t y l y and only one of t h e i r three daughters was a f f e c t e d .  Barrer (1947) on the other hand saw a f a m i l y  i n which both parents had l e f t ulnar d u p l i c a t i o n and t h e i r s i x c h i l d r e n were s i m i l a r l y affected.  The chances were estimated to be 91 out of 100  l e a s t one of the s i b s was homozygous.  that at  Thus the extent of d u p l i c a t i o n expressed  69  by the homozygote must be i n d i s t i n g u i s h a b l e from that.of the for  heterozygote.  the type of ulnar Polydactyly presented by that f a m i l y . Hypotheses were advanced to account f o r i r r e g u l a r dominant i n h e r i t a n c e  and sporadic occurrences of p o s t a x i a l Polydactyly.  Bateson ("1909) postulated  Polydactyly was due to dominant f a c t o r s which could be i n h i b i t e d or suppressed by other f a c t o r s .  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 r e s u l t e d from the operation of cumulative f a c t o r s whereas l e s s w e l l developed accessory f i f t h f i n g e r s were due to one Mendelian f a c t o r whose action could be suppressed•by other f a c t o r s (Sverdrup,  1922).  Examination of the  Snyder (1929) pedigree prompted Gates (1946) to remark that expression of Polyd a c t y l y might require two "gene" doses i n some f a m i l i e s but only a s i n g l e dose i n others.  In the l a t t e r instance penetrance would probably be  low.  P i p k i n and P i p k i n (1 946) postulated expression might'depend on the i n t e r a c t i o n of modifying genes with a s i n g l e 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 p o s t a x i a l d i g i t s would r e s u l t from the cooperative a c t i o n of the two genes. was adopted by Walker (196'1) who  The two-gene hypothesis  designated the genes responsible P and  A.  The frequency of P was to be low whereas A would have a moderately high frequency. I n d i v i d u a l s 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 r a i s e d that the  accessory gene might be associated with another anomaly ( P i p k i n & P i p k i n , 1946), or might be detectable only i n the presence of the dominant Polydactyly gene (Walker, 1961 ).  I t has also been postulated p o s t a x i a l d u p l i c a t i o n may  be  determined by more than two l o c i , p o s s i b l y with genes of "major e f f e c t " and genes of "minor e f f e c t " both operating (Mohan, 1969). i n t o the realm of polygenic i n h e r i t a n c e .  Such a system would f a l l  70 V a r i a b i l i t y i n expression of p o s t a x i a l 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 d i f f e r e n c e e x i s t e d between two morphologically d i s t i n c t forms of d u p l i c a t i o n which were designated type A and type B.  Type A Polydactyly r e f e r r e d 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 f i n g e r i n s e r t e d between f i n g e r s four and f i v e . 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 f i n g e r .  Sverdrup  Type B  accessory f i f t h f i n g e r s had no bony connection with the ulnar border of the hand but might contain o s s i f i e d elements. described as a pedicle or s k i n tag.  This form of d u p l i c a t i o n may  One perplexing t h i n g was accessory  be fifth  toes were equally w e l l developed among i n d i v i d u a l s with type A as i n d i v i d u a l s with type B ulnar d u p l i c a t i o n . Among o f f s p r i n g of A type i n d i v i d u a l s Sverdrup found an excess of a f f e c t e d c h i l d r e n with type A or type B d u p l i c a t i o n .  The  r a t i o of a f f e c t e d to normal c h i l d r e n of B type i n d i v i d u a l s was l e s s than or equal to one, and i t was postulated ulnar d u p l i c a t i o n would be l i m i t e d to type B P o l y d a c t y l y . Although the hypothesis i s not e n t i r e l y s a t i s f a c t o r y i t has often been r e f e r r e d to i n the l i t e r a t u r e .  The f a m i l y on which i t was based has a couple  of i n c o n s i s t e n c i e s i n the type of Polydactyly expressed; kindred 7 of Woolf and Woolf (1970) and f a m i l y number 127 of the B.C.  study are c l e a r l y  exceptions.  I t can be questioned whether two g e n e t i c a l l y 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 r e s u l t from one gene (two genes i f -  p o s t u l a t i n g a two-gene system) which i s g r e a t l y influenced by the genetic m i l i e u and environmental f a c t o r s (Odrione, 194-3; Mohan, 1969).  Another possible  explanation considers v a r i a b i l i t y of expression to be c h a 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 n a t u r a l l y unstable time of a c t i o n 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 a c t i o n of the main gene(s) ( C a l l a n , 1942). Regardless of whether the pedigree of Sverdrup (1922) demonstrated i t , the existence of a g e n e t i c a l l y d i s t i n c t , c o n s i s t e n t l y rudimentary type of ulnar Polydactyly (type B) as postulated i s supported by published (Johnston & Davis, 1953;  Walker, 1961)  as w e l l as the B.C.  pedigrees  results.  The  f i n d i n g s of Simpkiss and Lowe (1961 ) would i n d i c a t e f i b u l a r d u p l i c a t i o n 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 p o s t a x i a l  P o l y d a c t y l y appears to be synpolydactyly  which has been noted to have an auto-  somal ' dominant mode of inheritance ( B e l l , 1930; Two  Temtamy, 1966TD)L  types of d u p l i c a t i o n have been recognized among cases of thumb Poly-  dactyly.  In f a m i l i e s with t r i p h a l a n g e a l d u p l i c a t i o n , autosomal dominant i n -  heritance with f a i r l y high penetrance has often been seen ( s t r u t h e r s , McKellar, 1870; Ecke, 1962;  Atwood & Pond, 1917;  Mueller, 1936;  Temtamy, 1966b; Woolf & Woolf, 1970).  associated with t h i s type of d u p l i c a t i o n .  Haas, 1939;  1863;  Hefner,  1940;  T i b i a l Polydactyly may  be  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 t r i p h a l a n g e a l nature are a c t u a l l y Polydactyly the index f i n g e r (Penhallow, 1928; 1966b).  Manoiloff, 1931;  of  James & Lamb, 1963; Temtamy,  These pedigrees also suggest autosomal dominant i n h e r i t a n c e .  The  forms of r a d i a l P o l y d a c t y l y seen i n pedigrees with t r i p h a l a n g e a l d u p l i c a t i o n may  be extremely v a r i a b l e and d u p l i c a t i o n i s not n e c e s s a r i l y of a t r i p h a l a n -  geal nature i n a l l a f f e c t e d i n d i v i d u a l s . A p o s i t i v e f a m i l y h i s t o r y 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 t r i p h a l a n g e a l 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 d e v i a t i o n of the thumb noted i n the pedigrees  of Pot't (1884), Rudert (1938) and De Marinis and Sobbota (1957) suggests  tri-  phalangeal d u p l i c a t i o n . 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 a c t i o n 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 s i b s of p r o p o s i t i 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 s i b s of h i s probands would be expected to have thumb Polydactyly.  I n 32 r a d i a l cases there were 94 s i b s , none of whom were affected.  However, the occurrence of an accessory thumb i n the uncle of one proband was considered i n d i c a t i v e of polygenic i n h e r i t a n c e . Both post- and p r e a x i a l d u p l i c a t i o n occur i n one s p e c i a l type of Polydactyly, polysyndactyly (Lenglen, 1877; P f i t z n e r , 1898; Atkinson, 1901; Thomsen, 1927; B e l l , 1930; M c C l i n t i c , 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. polysyndactyly are i n h e r i t e d as a dominant t r a i t with v a r i a b l e e x p r e s s i v i t y rather than chance a s s o c i a t i o n of determining f a c t o r s f o r syndactyly and f o r postand p r e a x i a l Polydactyly (Temtamy, 196"6b).  Review of the aforementioned  pedigrees suggests nonpenetrance i s uncommon, however i t can occur (proband number 78).  C.  Genetic f a m i l y h i s t o r i e s :  results  Evidence suggests that i n the f a m i l i e s of 32 of the 1:38 probands there i s another i n d i v i d u a l with Polydactyly.  Considering only probands f o r whom a  genetic h i s t o r y has been s p e c i f i c a l l y taken there are 30 out of 89 (34 a positive family history.  with  A comparison of the number of cases with a p o s i -  t i v e f a m i l y h i s t o r y according to type of d u p l i c a t i o n presented by the proband  73  i s given i n Table XVIII.  This table d i s t i n g u i s h e s cases with m u l t i p l e con-  g e n i t a l anomalies. Probands with r a d i a l d u p l i c a t i o n whose family h i s t o r y appears to be p o s i t i v e f o r Polydactyly are numbers 1 0 , 1 8 , 1 9 , and 2 9 .  The c l e a r e s t case  i s number 18 where the maternal grandfather was examined and had a supernumerary thumb reported to be i d e n t i c a l t o that of the proband.  The mother of  proband number 2 9 , a c h i l d with t r i p h a l a n g e a l d u p l i c a t i o n , t o l d the p u b l i c h e a l t h nurse there was a h i s t o r y of supernumerary d i g i t s i n the family.  How-  ever the mother d i d not cho.ose to p a r t i c i p a t e i n the study and a d d i t i o n a l a f f e c t e d i n d i v i d u a l s were not s p e c i f i e d .  I t i s l i k e l y the a f f e c t e d person(s)  belonged to the maternal side of the f a m i l y since the proband's parents were not married.  I n f a m i l y number 10 the mother i n d i c a t e d the maternal grandmother  had t o l d her an i n f a n t with Polydactyly had previously been born i n the family but she d i d not know the exact k i n s h i p between that c h i l d and her baby. The h i s t o r y of case number 19 i s l e a s t c l e a r .  I n a p e d i a t r i c c o n s u l t a t i o n 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 m u l t i p l e congenital anomalies f o r whom family information was a v a i l a b l e have a p o s i t i v e family h i s t o r y of Polydactyly.  This h i s t o r y i s f u l l y documented  f o r one family only ( 1 / 1 9 , 5 f). Fourteen probands with ulnar Polydactyly have a p o s i t i v e family h i s t o r y of supernumerary d i g i t s .  Probands without m u l t i p l e congenital anomalies whose  a f f e c t e d r e l a t i v e s also had ulnar d u p l i c a t i o n are numbers 4 0 , 5 5 , 5 6 , 61 , 6 7 , 74 and 9 0 .  Information  on the a d d i t i o n a l a f f e c t e d persons i n f a m i l i e s 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 X V I I I .  Cases w i t h a P o s i t i v e Family H i s t o r y of Polydactyly  Families interviewed . cases without mma* Type of duplication  No. of cases  +PH  -FH  cases w i t h mma +FH  -PH  Families not interviewed cases without mma +FH  PH unk  cases w i t h mma FH unk  radial  31  15  tibial  6  3  ulnar  54  11  17  4  17  fibular  24  5  9  2  8  ulnar-fibular  16  5  3  2  1  2  4  1  unknown  Note:  7  1 *•* 3  1  1 •*•*•*  Cases are l i s t e d according to the type of d u p l i c a t i o n presented by the proband.  ^ m u l t i p l e major anomalies **from medical records, case number 19 ***from p u b l i c h e a l t h records, case number 136  75 A d d i t i o n a l a f f e c t e d persons w i t h other than ulnar Polydactyly were noted i n family 85 ( t i b i a l d u p l i c a t i o n ) , f a m i l y 87 ( r a d i a l d u p l i c a t i o n ) , family 86 (ulnar and f i b u l a r , ? r a d i a l d u p l i c a t i o n ) and f a m i l y 78 (ulnar, t i b i a l and ? radial duplication).  Family 86 i s considered  an example of the v a r i a b l e ex-  pression of u l n a r - f i b u l a r Polydactyly, one s i b presenting ulnar and d u p l i c a t i o n and three sibs presenting u l n a r .  fibular  The s i g n i f i c a n c e of an e x t r a -  o r d i n a r i l y wide thumb i n two f a m i l y members i s d i f f i c u l t to assess and may coincidental.  There i s no h i s t o r y of t i b i a l Polydactyly to suggest the family  presents polysyndactyly  as there i s i n f a m i l y 78.  Probands with m u l t i p l e congenital anomalies who sib are cases numbers 43 (trisomy  have a s i m i l a r l y a f f e c t e d  syndrome) and 73 ( 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). trisomy  be  syndrome.  Proband 46  had  The paternal grandmother of the c h i l d has f i b u l a r d u p l i -  c a t i o n ; t h i s i s the only anomaly she i s known to present. A p o s i t i v e family h i s t o r y of Polydactyly was fibular duplication.  found f o r f i v e probands with  In three f a m i l i e s , numbers 99, 104 and 105, an a d d i t i o n a l  a f f e c t e d person had f i b u l a r Polydactyly. • Supernumerary d i g i t s were polysyndactylous i n f a m i l i e s 99 and 104.  Information "regarding f a m i l y 104 was  obtained  through the p u b l i c health nurse and i t i s unknown whether there may have been a d d i t i o n a l a f f e c t e d family members. Kinship of the two a f f e c t e d persons i n family 105 i s f a i r l y d i s t a n t , the c l o s e s t common ancestor known to the proband's parents i s back four generations.  The second a f f e c t e d person was not examined  nor could the account be confirmed by a d d i t i o n a l sources. An a d d i t i o n a l a f f e c t e d person i s known i n family 93, a s i b with ulnar d u p l i c a t i o n , p l a c i n g t h i s f a m i l y among u l n a r - f i b u l a r cases.  The f i f t h f a m i l y ,  number 110, has a long h i s t o r y of u l n a r - f i b u l a r Polydactyly i n c l u d i n g one case which presented u l n a r , 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 s i b who have two p o s t a x i a l accessory d i g i t s on a s i n g l e limb.  76 Eight probands with u l n a r - f i b u l a r Polydactyly have a family h i s t o r y 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 d u p l i c a t i o n i s  known i n family 119; t h i s case was mentioned i n the family interview and could not be confirmed by other sources.  A d d i t i o n a l i n d i v i d u a l s with f i b u l a r and  with u l n a r - f i b u l a r d u p l i c a t i o n are known i n family 127; and there are individuals w i t h ulnar Polydactyly i n f a m i l i e s 120, 121, and 122. Probands with m u l t i p l e congenital anomalies are:  number 125, a c h i l d with giant c e l l h e p a t i t i s i n  whose family there are a d d i t i o n a l a f f e c t e d persons; number 131, whose s i b i s s i m i l a r l y a f f e c t e d with Laurence-Moon-Biedl syndrome; and number 124 (polydactyly/imperf orate anus/vertebral anomalies syndrome) whose father has u l n a r fibular 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 p o s i t i v e family h i s t o r y would appear to be w i t h i n 5 to 1 9 ^ , depending on the s u b s t a n t i a t i o n required a h i s t o r y i s accepted as p o s i t i v e .  before  Considering b i - and t r i p h a l a n g e a l d u p l i c a -  t i o n separately, f o r two out of three cases with t r i p h a l a n g e a l thumbs there i s some family information known.  Evidence suggests that accessory d i g i t s have  p r e v i o u s l y occurred i n one of the two f a m i l i e s . Among probands with biphalangeal duplicated thumbs, i t appears that 18 % (3/17) have a p o s i t i v e family history.  There was no family h i s t o r y of Polydactyly among the 24 r a d i a l cases  of Tan (1969). Among ulnar cases without m u l t i p l e congenital anomalies 39 % (11/28) are known to have a p o s i t i v e family h i s t o r y of Polydactyly, and 29 % (7/24) have a p o s i t i v e h i s t o r y of ulnar Polydactyly.  Affected members of family number  78 are believed to present v a r i a b l e expression of polysyndactyly; i n t h i s pedigree the anomaly appears to be i n h e r i t e d as a dominant t r a i t with incomp l e t e penetrance.  I t i s possible the presence of p r e a x i a l Polydactyly i n the  77 h i s t o r y of cases numbers 84 and. 86 i s c o i n c i d e n t a l , however Woolf and Woolf (1970) report p o s t a x i a l and p r e a x i a l Polydactyly  (R r a d i a l ) occurring  separately  i n t h e i r kindred 8 and a -number of s i m i l a r instances have been described (Struthers, 1863; Wilson, 1896; A t t l e e , 1907; Sysak, 1928; C a l l a n , 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 m u l t i p l e congenital anomalies, have a p o s i t i v e family h i s t o r y of Polydactyly and 25 f (3/12) have a h i s t o r y of f i b u l a r Polydactyly.  This i s  i n contrast to t i b i a l d u p l i c a t i o n but s i m i l a r to the f i n d i n g s 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 f a m i l y h i s t o r y of Polydactyly. Five out of eight of the probands without m u l t i p l e congenital  anomalies  with u l n a r - f i b u l a r Polydactyly have a family h i s t o r y of accessory d i g i t s . Including f a m i l i e s 86, 93, and 110, a p o s i t i v e h i s t o r y was given f o r eight out of 11 f a m i l i e s  {lJ$>)  i n which t h e r e . i s both ulnar and f i b u l a r d u p l i c a t i o n .  In only one of these families,- number 110, do a f f e c t e d persons nearly always present u l n a r - f i b u l a r d u p l i c a t i o n . P o s t a x i a l cases without m u l t i p l e congenital anomalies which have a p o s i t i v e h i s t o r y comprise 42 f> (21/50) of the p o s t a x i a l cases f o r which there i s i n f o r mation regarding the genetic family h i s t o r y .  For comparison, Woolf and Woolf  (1970) found among s u r g i c a l cases of p o s t a x i a l d u p l i c a t i o n 37 fo (7/19) with a family h i s t o r y of accessory d i g i t s ; i n the Singapore study only one out of 11 p o s t a x i a l cases (9 f ) had a p o s i t i v e family h i s t o r y (Tan,  1969).  I t i s inter-  e s t i n g to speculate whether these f i g u r e s might r e f l e c t a basic difference i n p r i n c i p a l f a c t o r s underlying  e t i o l o g y of p o s t a x i a l cases i n a predominantly  Caucasian population compared with a  predominantly Chinese  population.  78 E.  Penetrance:  r e s u l t s and d i s c u s s i o n  Review of the genetic h i s t o r i e s of probands with p o s t a x i a l Polydactyly without m u l t i p l e congenital anomalies who have a p o s i t i v e f a m i l y h i s t o r y of p o s t a x i a l accessory d i g i t s (polysyndactyly excluded), reveals some i n t e r 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 However among females who transmitted the t r a i t , few expressed i t .  equal.  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 f o r the probands' parents and f o r i n d i v i d u a l s i n preceding generations who are.assumed to have transmitted Polydactyly.  Cases numbers 85 - 87. have not been included i n the table due to the  f a c t that d i g i t a l anomalies noted i n i n d i v i d u a l s outside the probands' s i b s h i p s are confined to the p r e a x i a l border whereas the proband and s i b s have p o s t a x i a l duplication.  I n these three f a m i l i e s and i n f a m i l y number 93 no one i n pre-  ceding generations  can be shown to have transmitted p o s t a x i a l Polydactyly.  Prom the r e s u l t s i t appears p o s t a x i a l 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 ( p o s t a x i a l 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 p o s t a x i a l d u p l i c a t i o n . These inferences regarding sex r a t i o are somewhat l e s s c l e a r when i n d i v i d u a l s i n previous generations are included i n the f i g u r e s . Pedigrees of the p o s t a x i a l s u r g i c a l cases of Woolf and Woolf (1970) demonstrate the same phenomena regarding penetrance.  In 14 s i b s h i p s 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 Bather  Penetrant  Nonpenetrant  Total  .  7  2*  9  male i n preceding generations  6  2+4'*  12  mother  2  5  7  female i n preceding generations  3  2+2*  7  18-  17'  total  35  *common ancestor of proband and affected relative three or more generations removed (cases numbers 74 andH05)  80 digits.  Adding data from Woolf and Woolf (1970) to the B.C. f i n d i n g s provides  a l a r g e r sample of p o s t a x i a l pedigrees, although i t i s now biased i n a s c e r t a i n ment of s u r g i c a l 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 ); t h e ' r a t i o of penetrance to nonpenetrance among men and women remains about one (-27 : 22) whereas t h 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 u l n a r , f i b u l a r and u l n a r - f i b u l a r pedigrees separately f o r penetrance among males and females.  Ascertainment bias i n the study of Woolf and Woolf makes  i t inappropriate to pool cases f o r such an a n a l y s i s . 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 f i n d i n g s may be more c h a r a 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 w i t h a f a m i l y h i s t o r y of ulnar (2.3), f i b u l a r (1.9) and u l n 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 f a m i l y h i s t o r y of accessory thumbs c l e a r l y documented.  I n that case thumb Polydactyly i s  expressed by the maternal grandfather and the proband but nonpenetrant i n the c h i l d ' s mother.  There i s information suggesting a p o s i t i v e h i s t o r y f o r three  other probands with duplicated thumbs.  A maternal r e l a t i v e was presumably  a f f e c t e d i n a t l e a s t two of these f a m i l i e s 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 w e l l .  The pedigree of Sinha (1918) also demonstrates  maternal nonpenetrance i n a f a m i l y with u n i l a t e r a l r a d i a l Polydactyly a f f e c t i n g three generations.  Occurrence of t r i p h a l a n g e a l thumbs was not mentioned.  P o s t a x i a l Polydactyly unassociated with m u l t i p l e anomalies can also be examined to f i n d whether the proportion of a f f e c t e d c h i l d r e n by sex among f a m i l i e s with a p o s i t i v e h i s t o r y of ulnar or f i b u l a r d u p l i c a t i o n i s equal to  81 the proportion among f a m i l i e s 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 t r a n s m i t t i n g the t r a i t or whether that parent expresses i t ? Despite the f a c t 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 c h i l d r e n i n the probands' s i b s h i p s plus the proportion i n previous generations f o r which e i t h e r (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 s i b s were polydactylous or are assumed to have transmitted the t r a i t .  This data i s provided i n Table XX.  Pedigrees w i t h a. p o s i t i v e h i s t o r y of ulnar or f i b u l a r Polydactyly have been grouped together.  .Among them are three' f a m i l i e s i n whom the common  ancestor was three or four generations back.  Findings f o r ulnar and f i b u l a r  Polydactyly are strongly influenced by these cases. among c h i l d r e n of polydachylous  The proportion a f f e c t e d  fathers ( 1 / 2 4 ) and of unaffected fathers who  have a p o s i t i v e family" h i s t o r y (2/28) i s not appreciably d i f f e r e n t .  Furthermore  the l a t t e r f i g u r e should be somewhat lower since the number of c h i l d r e n i n three s i b s h i p s was unknown and could not be included.  The percentage of a f f e c t e d  c h i l d r e n among o f f s p r i n g of women t r a n s m i t t i n g ' P o l y d a c t y l y appears to be very s i m i l a r to f i g u r e s f o r men.  The f i n d i n g s 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 d i f f e r e n c e i n sex ratio among a f f e c t e d . c h i l d r e n of males and of females; fathers appear to transmit Polydactyly more commonly to sons than daughters. In f a m i l i e s with a h i s t o r y of u l n a r - f i b u l a r Polydactyly there are no instances of unaffected males t r a n s m i t t i n g the t r a i t , although i n such f a m i l i e s women w i t h normal d i g i t s have had a f f e c t e d sons or daughters. of the c h i l d r e n of polydactylous fathers have been a f f e c t e d .  Fifty  percent  The percentage  of polydactylous c h i l d r e n (27.7 f°) born to mothers w i t h u l n a r - f i b u l a r d u p l i c a t i o n 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 A f f e c t e d I n d i v i d u a l s  Number of c h i l d r e n polydactylous males A.  females  Percentage normal number of d i g i t s affected —: excluding males females sex unk. proband  polydactylous fathers ulnar or f i b u l a r  1  (4)  -  (0  9  ulnar-fibular  5  (1)  9  (1)  6  ulnar or f i b u l a r  -  (-)  -  (0  2  ulnar-fibular  4  (1)  1  (-)  1  1  (2)  1  (-)  -  (-)  - (-)  ulnar or f i b u l a r  -  (2)  1  (-)  ulnar-fibular  1  (D  -  (2)  4  (1)  - (-)  4  (2)  3  4.3  14  50.0  polydactylous mothers  B.  27.7  unaffected f a t h e r s , + family history ulnar or f i b u l a r ulnar-fibular unaffected mothers, + family history  C.  unaffected  11  15  7.1  4  7  8.3  9  6  6.2  1  2  11  24  parents,  - family h i s t o r y ulnar or f i b u l a r ulnar-fibular Note:  (-)  Number of probands t o t a l e d separately i n parenthesis.  57.1  14  12.5  83 have a family h i s t o r y of t h i s type of d u p l i c a t i o n , however the discrepancy between the proportion  of polydactylous c h i l d r e n among o f f s p r i n g of a f f e c t e d  and unaffected women may w e l l be due to the small number of sibships analyzed. There i s .no excess of a f f e c t e d males among the c h i l d r e n with u l n a r - f i b u l a r Polydactyly  t o t a l e d 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 d u p l i c a t i o n . I t can be seen among interviewed  f a m i l i e s with two or more polydactylous  i n d i v i d u a l s (without m u l t i p l e anomalies), i n few f a m i l i e s were a l l a f f e c t e d persons i n the probands' s i b s h i p s .  Considering cases of ulnar d u p l i c a t i o n and  f i b u l a r d u p l i c a t i o n together, i n only one out of 28 cases without a h i s t o r y of p o s t a x i a l Polydactyly i n a previous generation was a s i b of the proband a f f e c t e d (1/81 s i b s ) .  This would suggest that the chances of a second a f f e c t e d c h i l d  i n a family with a negative h i s t o r y i s quite low, approximately 1.2$. Of course i t must be remembered that some f a m i l i e s i n the study were probably not yet complete.  Among u l n a r - f i b u l a r cases, two out of f i v e probands without a  h i s t o r y of Polydactyly p r i o r to the proband's s i b s h i p have two or more a f f e c t e d 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 a f f e c t e d . of i n t e r e s t are the f i g u r e s f o r r a d i a l cases.  Also  Nineteen probands without  m u l t i p l e congenital anomalies, which includes the four cases with a p o s i t i v e family h i s t o r y , had 56 s i b s , none of whom were  F.  polydactylous.  Conclusions and speculation Although a d d i t i o n a l pedigrees are necessary i n order to define the genetic  component i n the e t i o l o g y of d i f f e r e n t jiypes of Polydactyly unassociated with m u l t i p l e congenital anomalies, the B.C. data points out several i n t e r e s t i n g features.  The wide d i f f e r e n c e i n the B.C. f i n d i n g s between the percentage of  p o s i t i v e family h i s t o r i e s among probands a f f e c t e d with u l n a r - f i b u l a r (73 fo) and  84 u l n a r (29 %) or f i b u l a r (25  types of Polydactyly could suggest (a) polygenic  inheritance of p o s t a x i a l 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, c o n s t i t u t i n g a high r i s k group or (b) i n h e r i tance of u l n a r , f i b u l a r and u l n a r - f i b u l a r d u p l i c a t i o n 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 f a c t that the r i s k f o r s i b s of an a f f e c t e d c h i l d with a negative family h i s t o r y of the t r a i t i s less (1.2 fo) than the r i s k f o r s i b s of a proband with an a f f e c t e d r e l a t i v e (approximately 6.6 % ) .  Furthermore pedigrees  i n which a f f e c t e d i n d i v i d u a l s are d i s t a n t cousins are t y p i c a l of polygenic i n h e r i t a n c e , however dominant inheritance with reduced penetrance could present the same pattern.  Among u l n a r - f i b u l a r cases the percentage of a f f e c t e d 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) s t r o n g l y suggest dominant inheritance.  Yet the sharp reduction  i n percentage of a f f e c t e d c h i l d r e n of unaffected mothers compared to a f f e c t e d mothers would be expected with polygenic inheritance (Carter, 1969)The method of Edwards (i960, 1969) to c a l c u l a t e the expected number of a f f e c t e d s i b s f o r a polygenic t r a i t with 100 % h e r i t a b i l i t y gives the f o l l o w i n g . Combined incidence of ulnar and f i b u l a r Polydactyly i n B.C. 1,000  live births; p  2  = 0.0219.  equals 0.47  per  Consequently 2.2 % of the 107 s i b s of ulnar  and f i b u l a r cases would be expected to be polydactylous.  Three c h i l d r e n have  accessory d i g i t s , an observation which f i t s the t h e o r e t i c a l value of 2.4 well.  For u l n a r - f i b u l a r d u p l i c a t i o n (p = 0.08  per 1,000; p  2  = 0.009) no poly-  dactylous i n d i v i d u a l s would be expected among 44 s i b s ( t h e o r e t i c a l value, whereas 11 s i b s with accessory d i g i t s were observed. cases (p = 0.55  per 1,000; p  2  very  0.4)  Lumping a l l p o s t a x i a l  = 0.0235) the expected number of a f f e c t e d s i b s  would be 3.6 c h i l d r e n , considerably lower than the observed number of 14.  This  provides f u r t h e r 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 u l n a r , f i b u l a r and u l n a r - f i b u l a r d u p l i c a t i o n does not suggest that u l n a r - f i b u l a r Polydactyly r e s u l t s from the coincident occurrence of ulnar and of f i b u l a r Polydactyly, nor does t h i s seem l i k e l y from the segregation patterns observed i n various f a m i l i e s . 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 u l n a r - f i b u l a r - d u p l i c a t i o n , the d i s t i n c t i o n i s s t i l l u s e f u l and i t i s the inheritance and/or operation of f a c t o r s responsible f o r v a r i a b l e express i o n which are under a n a l y s i s . Therefore i t i s the view of the i n v e s t i g a t o r that there e x i s t at l e a s t three d i s t i n c t types of p r e a x i a l Polydactyly and f i v e types of p o s t a x i a l 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 u l n a r -  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 a f f e c t e d s i b s , (c) a tendency f o r accessory ulnar d i g i t s to be well-developed be syndactylous, B.C.  or accessory f i b u l a r d i g i t s to  or (d) a sex r a t i o considerably d i f f e r e n t from one.  f i n d i n g s 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 i n h e r i t a n c e . As yet there i s i n s u f f i c i e n t data f o r u l n a r - f i b u l a r Polydactyly'to j u s t i f y i  p o s t u l a t i n g anything other than autosomal dominant inheritance with reduced penetrance among females. single  I f the Polydactyly r e s u l t e d from the a c t i o n of a  gene, unequal proportions of a f f e c t e d o f f s p r i n g f o r polydactylous  and  86 " c a r r i e r " mothers could be due to a threshold of a polygenic nature or to segregation of f a c t o r s which i n h i b i t expression.  A model c o n s i s t i n g of two auto-  somal dominant genes would provide an explanation f o r nonpenetrance, but not f o r nonpenetrance p r i n c i p a l l y or e n 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 s e l e c t i v e advantage, h a l f of the c h i l d r e n of an a f f e c t e d male would not be expected to have Polydactyly unless the frequency of the accessory gene approached u n i t y . A two-gene model with an X-linked accessory gene recessive i n females and hemizygous i n males would give a 1.25 sex r a t i o when p equalled 0.8.  Forty percent  of the o f f s p r i n g of an a f f e c t e d male would be expected to have Polydactyly; the Polydactyly gene should be nonpenetrant among 20 % of the males who carry i t . F o r t y - f i v e percent of the o f f s p r i n g of polydactylous (50 fo males, 40 % females) whereas polydactylous  females would be a f f e c t e d  children'would.comprise 22.5 %  of the o f f s p r i n g of " c a r r i e r " women (25 % males, 20 % females). would be h a l f as frequent as women who expressed the t r a i t .  C a r r i e r women  When more family  data from incidence studies are a v a i l a b l e i t may be c l e a r e r which of these t h e o r i e s , i f any, best f i t s the f i n d i n g s f o r u l n a r - f i b u l a r and other types of Polydactyly which have an i r r e g u l a r dominant pattern of i n h e r i t a n c e .  87 VIII.  M u l t i p l e Congenital Anomalies Polydactyly has been noted i n a s s o c i a t i o n w i t h a number of congenital  malformations.  In some instances t h i s a s s o c i a t i o n i s probably f o r t u i t o u s  whereas i n others the anomalies appear to have a common e t i o l o g y .  The incidence  and nature of a d d i t i o n a l congenital anomalies among the probands of the B.C. study i s presented i n t h i s s e c t i o n and compared to the "general population". Types of d u p l i c a t i o n seen i n the probands with a d d i t i o n a l anomalies are summarized.  In a d d i t i o n 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 i n t e r e s t , i n c l u d i n g comments from B.C. data on syndromes diagnosed i n one or more probands, f o l l o w s .  A.  Introduction I t i s of i n t e r e s t to know whether i n f a n t s w i t h supernumerary d i g i t s have  a d d i t i o n a l 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 e f f e c t on  e i t h e r the f u n c t i o n 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  i n d 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 i n d i v i d u a l chosen at random.  Minor anomalies  occur independently and do not tend to c l u s t e r 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) supernumerary d i g i t s were considered to be e i t h e r a minor or a major anomaly depending upon the examiner's evaluation of the s e v e r i t y of the d u p l i c a t i o n .  This sub-  j e 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 a f f e c t e d persons of the same family and seen i n syndromes  associated'with supernumerary d i g i t s .  Furthermore an i n d 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 f i n g e r ( s ) and/or t o e s ( s ) .  As there seems to be no n a t u r a l dichotomy i n t o "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 r e f e r r e d to as a major or minor malformation i n the r e s u l t s which f o l l o w .  B. . Results Minor anomalies. major malformation. 12  To our knowledge 105 out of 138 c h i l d r e n do not have a  The presence of a s i n g l e minor anomaly has been noted i n  c h i l d r e n (12/105), nine boys and three g i r l s , and two minor anomalies i n one  a d d i t i o n a l boy.  As no s p e c i a l measures were taken to assess minor anomalies  i n the cohort the f i g u r e 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 ) , p r e a u r i c u l a r s k i n tags ( 2 ) , abnormal buttock crease (1 ) and a n t i mongoloid s l a n t of palpebral f i s s u r e s ( l ) .  Hernia and hemangiomas of the face  or neck were noted i n f i v e and three c h i l d r e n r e s p e c t i v e l y ;  these anomalies  were categorized as normal phenotypic v a r i a n t s by Marden et a l . (1964). In a d d i t i o n four c h i l d r e n had a tongue-tie c l i p p e d .  Dermatoglyphics were not  i n v e s t i g a t e d i n many of the B.C. c h i l d r e n and have not been included. I t should be noted that abnormal palmar creases accounted f o r approximately 30 % of the i s o l a t e d minor anomalies observed by Marden and colleagues. The 13 c h i l d r e n whose minor anomalies are-consistent w i t h those t a l l i e d i n the Madison, and Albany studies presented various forms of Polydactyly. D e s c r i p t i o n of the supernumerary d i g i t s i s given in' Table XXI.  Among c h i l d r e n  w i t h 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 s k i n tag duplicated d i s t a l phalanx  rudimentary d i g i t  Border L radial L radial R radial R ulnar B ulnar R ulnar, R f i b u l a r L ulnar, B f i b u l a r  one or more well-formed digits  B ulnar B fibular B ulnar, B f i b u l a r  unknown  B "feet"  No. of cases  90  w i t h p o s t a x i a l d u p l i c a t i o n i n v o l v i n g the hands and feet (3/16) and w i t h d u p l i c a t i o n of the thumb (4/31 ).  Few c h i l d r e n w i t h s o l e l y u l n a r (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 w i t h a minor anomaly tends to be rudimentary, rudimentary forms comp r i s e the bulk of the cases i n the study and t h i s would appear of l i m i t e d 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 a s s o c i a t i o n w i t h supernumerary d i g i t s , and w i t h 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 .  Single ma.jor anomalies.  (1964).  A s i n g l e major anomaly has been noted i n nine of  the polydactylous c h i l d r e n (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 d u p l i c a t i o n of a d i g i t ( 2 ) , (2),  strabismus ( 2 ) ,  cataract  c l e f t palate ( l ) , enlarged l i v e r (1) and hypoglycemia ( l ) .  The a s s o c i a t i o n of poly- and syndactyly inttwo cases i s probably not random. Although cases w i t h c l e f t palate and p o s t a x i a l or p r e a x i a l supernumerary  digits  have been described (see Table XXV) and the a s s o c i a t i o n of p o s t a x i a l 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. w i t h extra d i g i t s i s not c l e a r .  The s i g n i f i c a n c e of eye defect  In these f o u r cases and the remaining two  the occurrence of Polydactyly and a major anomaly may w e l l be due to independent events. ..Minor anomalies noted i n two c h i l d r e n are:  deformed f i f t h f i n g e r  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. of the supernumerary d i g i t s i s given i n Table XXII.  Description  The frequency of a s i n g l e  major anomaly among c h i l d r e n w i t h d i f f e r e n t types of Polydactyly i s :  91  Table XXII.  Type of Polydactyly Presented by Children with One Major Anomaly  Description duplicated d i s t a l phalanx  Border L radial B tibial  b i f i d proximal phalanx  B radial  pedicle  L ulnar R ulnar B ulnar  well-formed unknown  digit  L fibular B ulnar, B f i b u l a r  No. of cases  92  t i b i a l ( 1 / 6 ) , r a d i a l (2/31), u l n a r ( 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/l6).  Extent of d u p l i c a t i o n 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 w i t h the occurrence of well-formed extra d i g i t s than rudimentary ones.  This tends to mask the f a c t that i n some cases  undoubtedly the type of d u p l i c a t i o n i s d i c t a t e d by the same dysfunction as the  major anomaly.  M u l t i p l e major anomalies.  There are 24 c h i l d r e n i n the P o l y d a c t y l y study  w i t h two or more major malformations, 18 boys and 6 g i r l s . the  This i s 17 % of  cohort. In some cases the m u l t i p l e major anomalies presented by the poly-  dactylous c h i l d r e n have been recognized as a s p e c i f i c syndrome or c l i n i c a l entity.  Of these, i n a l l but perhaps the l a s t two, P o l y d a c t y l y i s known to  show more than a random a s s o c i a t i o n :  trisomy D^ syndrome ( j ) , Smith-Lemli-Opitz  .syndrome ( 3 ) , polydactyly/imperforate anus/vertebral anomalies syndrome  (l),  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 P o l y d a c t y l y ( l ) , syndrome ( l ) ,  Laurence-Moon-Biedl syndrome ( l ) ,  giant c e l l h e p a t i t i s ( l ) . etiology.  P i e r r e Robin anomaly ( l )  Down's and  In a d d i t i o n there are 12 cases a t t r i b u t e d to unknown  Seven of these have anomalies suggestive of one of the f i r s t three  syndromes above i n c l u d i n g one case which was noted to c l o s e l y resemble trisomy 17-18  syndrome and another casev/which was described as a form of c y c l o p i a .  P r i n c i p a l among anomalies i n the remaining f i v e cases are heart defect along w i t h other anomalies (4) and m u l t i p l e cephalic defects ( l ) .  As would be  expected, minor anomalies were commonly noted i n c h i l d r e n w i t h m u l t i p l e cong e n i t a l anomalies (18/22 or 82 % ) . Minor anomalies are given i n the case d e s c r i p t i o n s i n Appendix A. Supernumerary  d i g i t s i n c h i l d r e n w i t h m u l t i p l e major anomalies tend to  be more complete forms of d u p l i c a t i o n . Table X X I I I .  D e s c r i p t i o n of the d i g i t s i s given i n  A large number of c h i l d r e n w i t h m u l t i p l e major anomalies have  93  Table XXIII.  Type of Polydactyly Presented by Children with M u l t i p l e Major Anomalies  Description  Border  duplicated d i s t a l phalanx  R radial  pedicle  L radial R radial L ulnar B ulnar R fibular  one or more well-formed digits  R radial B fibular 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  unknown5  R ulnar L ulnar B ulnar R "hand" "Polydactyly"  No. of cases  .  u l n a r and f i b u l a r (7/16) Polydactyly.  94  In each case there i s at l e a s t 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 l e a s t one extra d i g i t described as well-formed. Thus 60  f> ( 7 / 1 2 )  of the probands with polydactylous hands and f e e t both have  m u l t i p l e major anomalies. anomalies.  This i s 29 f° of the c h i l d r e n with m u l t i p l e major  C h i l d r e n presenting ulnar and f i b u l a r d u p l i c a t i o n include one case  of giant c e l l h e p a t i t i s and one case each of Laurence-Moon-Biedl syndrome, Polydactyly/imperforate anus/vertebral anomalies syndrome and Smith-Lemli-Opitz syndrome. L i t t l e can be s a i d about the extent of d u p l i c a t i o n i n cases with ulnar supernumerary d i g i t s since among cases with d e s c r i p t i o n s the accessory were a l l termed pedicles ( 5 / 9 ) . d u p l i c a t i o n are Smith-Lemli-Opitz  digits  The syndromes seen i n probands with ulnar syndrome ( 2 ) , p o l y c y s t i c kidneys,  internal  hydrocephalus and p o s t a x i a l P o l y d a c t y l y ( l ) , and trisomy D.j syndrome.  The c h i l d  noted to resemble trisomy 17-18 syndrome also presented u l n a r d i g i t s .  Syndromes  diagnosed i n probands w i t h r a d i a l ( 4 ) and f i b u l a r ( 2 ) Polydactyly are Down's syndrome and P i e r r e Robin anomaly r e s p e c t i v e l y . D u p l i c a t i o n i n these two cases i s quite complete; i n a d d i t i o n a l cases w i t h r a d i a l ( 2 / 4 ) and f i b u l a r ( 1 / 2 ) Polyd a c t y l y the extra d i g i t s were described as p e d i c l e s . noted to present c y c l o p i a had r a d i a l Polydactyly.  I n a d d i t i o n the c h i l d  Further comment on t h i s  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 c h i l d r e n 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 f o r minor and major anomalies detectable by surface examination. w i t h no major malformation  Among 4 , 3 2 2 babies  there were 574 w i t h one •• minor anomaly and 35 w i t h  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 i n f a n t s .  The percentage of i n f a n t s  w i t h one minor anomaly who had an a d d i t i o n a l 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 i n f a n t s w i t h a s i n g l e 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 t h i s d i f f e r e n c e r e f l e c t s the examiners' i n t e r p r e t a t i o n of minor and major anomaly.  However the s i g n i f i c a n t f a c t 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 random d i s t r i b u t i o n . The d i f f e r e n c e i n means of a s c e r t a i n i n g 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 t h i s information was gleaned from medical records. There i s the suggestion however that supernumerary 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 f o r several reasons:  (a) among polydactylous c h i l d r e n the  low frequency of a d d i t i o n a l minor anomalies i n the absence of a major defect (9 f) compared to the frequency when one (approximately 22 fo) or more (approximately 82 fo) major anomalies are present does not suggest there i s a c l u s t e r i n g e f f e c t ; ( i t i s true however that medical records tend to be more complete f o r i n f a n t s w i t h serious malformations.); (b) the B.C.. f i g u r e (9 fo), taking i n t o account i t s minimal nature, i s not incompatible w i t h the frequency (26 fo) found f o r the random a s s o c i a t i o n of two minor anomalies (Hook & Petry, 1970); and (c) regarding c h i l d r e n with no major defect, the frequency of a d d i t i o n a l minor anomalies noted i n polydactylous c h i l d r e n 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 c h i l d r e n with supernumerary d i g i t s (24 $) have one or more major anomalies.  This includes anomalies detected a f t e r the new-  born period f o r those c h i l d r e n on whom a d d i t i o n a l information was a v a i l a b l e . These f i n d i n g s can be compared with the survey of 5,739 newborns by Mcintosh et a l . (1954)." Some of the c h i l d r e n were followed f o r f i v e years; at the conc l u s i o n of the study the incidence of major anomalies was 7.5 $. i n d i c a t e that a major defect occurs approximately  This would  34" times more frequently  among c h i l d r e n with Polydactyly. In order to compare the P o l y d a c t y l y study r e s u l t s w i t h those of Marden et a l . , two cases have been subtracted due to the f a c t that newborns i n the Madison study were not examined f o r c e r t a i n anomalies of the c e n t r a l nervous system, or the cardiovascular, g a s t r o i n t e s t i n a l and r e n a l systems. A f t e r t h i s c o r r e c t i o n i t appears a s i n g l e major anomaly.(5.0 fo) occurs four.times more frequently i n the polydactylous c h i l d r e n than i n the Madison newborn populat i o n (58/4,412 or 1.3 f°) and occurs about twice as often i n the Polydactyly group than i n Madison babies who have a minor anomaly (17/609 or 2.8 fo).  The  frequency of supernumerary d i g i t s and a s i n g l e major anomaly occurring together i s l e s s by h a l f however than the l i k e l i h o o d that a case of the Madison populat i o n with one major malformation would present one other major defect as w e l l . The percentage of c h i l d r e n i n the P o l y d a c t y l y group with two or more major malformations (24/138, 17 f>) i s approximately  25 times the frequency of  m u l t i p l e major anomalies i n i n f a n t s of the Madison population (32/4,412, 0.7$). And at l e a s t 73 f> (24/33) of the polydactylous c h i l d r e n with a major malformat i o n have m u l t i p l e defects i n contrast to a f i g u r e 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 w i t h P o l y d a c t y l y w i l l have a d d i -  t i o n a l minor anomalies or a s i n g l e major anomaly i s not much greater than that  97 of a c h i l d born w i t h 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 a d d i t i o n a l major anomalies. The B.C.  study has a greater frequency of c h i l d r e n with a d d i t i o n a l anomalies  than was found by Tan (1969) among 42 polydactylous i n f a n t s .  In the Singapore  study there were 7 cases with one or more a d d i t i o n a l anomalies: Creveld syndrome ( l ) , Down's syndrome ( 2 ) , anus (1), syndactyly of toes 4-5  trisomy D^ syndrome (1)  Ellis-van imperforate  ( l ) , and p r e a u r i c u l a r s k i n tag ( l ) . Postulating  that the i n f a n t w i t h imperforate anus was an unrecognized  case of P o l y d a c t y l y /  imperforate anus/vertebral anomalies syndrome, 12 fo (5/42) of the polydactylous c h i l d r e n had m u l t i p l e anomalies. In the study by Neel (1958), among 60 polydactylous c h i l d r e n , 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 s i n g l e a d d i t i o n a l major anomaly and seven cases (1T.6 fo) had m u l t i p l e congenital anomalies.  These, f i g u r e s show approximately a seven  f o l d increase i n the number of c h i l d r e n with major defect over the general population of Japanese i n f a n t s studied. The extraordinary incidence of m u l t i p l e congenital anomalies among c h i l d ren with supernumerary d i g i t s i s due to the f a c t that Polydactyly occurs i n a s s o c i a t i o n with a number of other malformations the product of t h e i r respective frequencies. d u p l i c a t i o n seen i n B.C.  at a frequency greater than  Comparison of the types of  probands with a d d i t i o n a l anomalies, given i n Table  XXIV, reveals one group of cases i n which there i s a greater a s s o c i a t i o n with a d d i t i o n a l anomalies.  Two-thirds of the cases of p o s t a x i a l d u p l i c a t i o n of  the hands and f e e t have a d d i t i o n a l 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.  P o s t a x i a l forms  tend to be b i l a t e r a l and a greater percentage of well-developed forms are associated with m u l t i p l e anomalies.  Thus i n some cases Polydactyly i s a good  98 Table XXIV.  Type of Polydactyly Associated with A d d i t i o n a l Congenital Anomalies  Type of duplication  No. of cases i n study  Minor anomaly only  One major anomaly  M u l t i p l e major anomalies  tibial  C6  -  1  -  1  radial  31  4  2  4  10  ulnar  54  4  4  9  17  fibular  24  1  1  2  4  ulnar & f i b u l a r  ;i;_6  3  1  7  •11  7  1  -  2*  138  13  unknown total *one of hand  • 9 '-"'  24  3 46  i n d i c a t o r of extensive developmental disturbances leading to m u l t i p l e congenit a l anomalies.  D.  Syndromes The d i s t r i b u t i o n of cases w i t h m u l t i p l e major anomalies regarding type of  P o l y d a c t y l y expressed would seem i n large measure dependent on the incidence of various syndromes and the frequency of P o l y d a c t y l y 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 d u p l i c a t i o n are c h a r a c t e r i s t i c of s e v e r a l 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.  F i b u l a r Polydactyly, d i s t i n c t from the v a r i a b l e expression of u l n a r -  f i b u l a r P o l y d a c t y l y , 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 p r e a x i a l Polydactyly, t i b i a l d u p l i c a t i o n i s  g e n e r a l l y l i m i t e d to syndromes w i t h polysyndactyly whereas r a d i a l d u p l i c a t i o n 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 a d d i t i o n a l syndromes.  Down's syndrome.  Mongolism was described by Down i n 1866 and has a  number of d i s t i n g u i s h i n g features i n the newborn which are presented i n Table XXVI.  Trisomy of chromosome 21 was noted i n p a t i e n t s with the syndrome by  Lejeune et a l . (1959); few reported i n d i v i d u a l s w i t h the c l u s t e r of stigmata seen i n the syndrome have had no recognizeable excess of chromosome (21) m a t e r i a l ( H a l l , 1964).  Although the developmental anomalies e f f e c t e d by com-  p l e t e or p a r t i a l trisomy of the number 21 chromosome do not u s u a l l y include Polydactyly, i t does occur.  In a.study i n Massachusetts, Fabia and D r o l e t t e  (1970) ascertained 2,774 l i v e b o r n i n f a n t s w i t h Down's syndrome born between 1 January 1950 and 1 January 1967, an incidence of 1.32  per 1,000  live births.  Table XXV.  Syndromes and Anomaly Complexes Associated with Duplicated D i g i t s Radial T i b i a l Ulnar F i b u l a r U l n ^ f i b . Postax. Polvsynd y P ° y Unusual d u p l i c . polyd. polyd. polyd. polyd. polyd. * t i b i a l dup. polyd. S  n  1  d &  J  Congenital anemia & triphalangeal thumbs (Aase & Smith, 196©) B/G t r a n s l o c a t i o n associated with m u l t i p l e congenital anomalies ( F i t z g e r a l d & Neal, 1964)  triph ? biph X  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 (Bass, 1968)  biphal  Translocation 3/B syndrome (Walzer et a l , 1966)  biphal  Triphalangeal thumbs with t i b i a l defect t r i p h & p r e a x i a l Polydactyly ( S a l z e r , 1960) Triphalangeal thumbs & great toes associated w i t h other anomalies (Qazi-& Smithwick, 1970)  triph  Holt-Oram syndrome  triph ? biph  Thalidomide embryopathy  triph ? biph  X triph  X 7th  Pelizaeus-Merzbacher's disease w i t h 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  triph  Polydactyly/imperforate-anus/vertebral anomalies syndrome  triph biphal  X X  X  7th  X o o  Table XXV.  (continued)  Radial T i b i a l Ulnar E i b u l a r U l n - f i b . duplic. polyd. polyd. polyd, polyd.  Cyclopia  X  Down's syndrome  X  Trisomy 1 7 - 1 8 syndrome  X  broad  X  P o l y d a c t y l y w i t h median c l e f t upper l i p  X  X  syndrome  X  X  X  7th  X  7th  X  X  X  P o l y d a c t y l y with c l e f t l i p and/or palate.  X  X.  X  Laurence-Moon—Biedl syndrome  X  X  X  X  X  X  X  (OPD I I )  7th X  X (fib.) X (fib.)  Rubinstein-Taybi syndrome  X (fib.)  Prontodigital  X (fib.)  syndrome  Polysyndactyly with p e c u l i a r s k u l l shape  J  X  X  Mohr syndrome  v  X  E l l i s van Creveld syndrome  syndrome I  J  X X  Oro-facial—digital  n  X  D trisomy syndrome  Biemond's syndrome I I  n  X  Microphthalmia, anpphthalmos with d i g i t a l anomalies.  Smith-Lemli-Opitz  Postax. _ Synpolyd & Unusual polyd. Polysynd. t i b i a l dup. polyd.  X  X  X  Table XXV.  (continued)  Radial  T i b i a l Ulnar F i b u l a r U l n - f i b . Postax.  polyd.  polyd. polyd. polyd.  polyd.  Goltz;'s syndrome Noack's syndrome (ACPS i ) Carpenter's  polyd.  Synpolyd &  p  •  t i b i a l dup.  /  X X  Waardenburg's type ACS:  Hexadactyly, mandibular f i s s u r e & o l i g o d o n t i a (Weyers, 1953)  X X X X  P i e r r e Robin anomaly with Polydactyly  X  D i a b e t i c embryopathy (Lenz, 1966) Thoracic asphyxiant dystrophy  polyd.  X  syndrome (ACPS I I )  P f e i f f e r ' s type ACSRobinson type ectodermal d y s p l a s i a (Robinson et a l , 1962)  Unusual  ? X X-  X  O l i v e r ' s syndrome ( O l i v e r , 1940)  X  P o l y c y s t i c kidneys, i n t e r n a l hydrocephalus & P o l y d a c t y l y (Simoupolis et a l , 1967)  X  P o l y d a c t y l y of the second metatarsal w i t h associated defects of the f e e t (Neel & Rusk, 1963)  X  F-form of aero—pectoro-vertebral d y s p l a s i a (Grosse et a l , 1969)  X  103  Table XXVI.  C a r d i n a l Features of the Newborn w i t h Down's Syndrome  hyperflexibility muscle hypotonia l a c k of Moro r e f l e x flat facial profile oblique p a l p e b r a l f i s s u r e s d y s p l a s t i c ears neck f o l d s simian crease d y s p l a s t i c middle phalanges d i g i t V d y s p l a s t i c pelves  Source:  H a l l (1964)  104 Among them were two females w i t h Polydactyly and f i v e males w i t h b i f i d thumb, a<> prevalence per 1,000 l i v e b o r n mongols of 0.8 and 2.1 r e s p e c t i v e l y . Tan (1969) found two polydactylous i n f a n t s w i t h Down's syndrome i n h i s study. Both i n f a n t s had u n i l a t e r a l thumb Polydactyly, one w i t h a b i f i d proximal phalanx r i g h t and the other w i t h a supernumerary thumb a r t i c u l a t i n g w i t h the l e f t f i r s t . metacarpal.  Another case w i t h an extra thumb was found among 38 mongols i n a  study of newborns i n Sweden ( H a l l , 1964).  One male i n f a n t (proband number 6)  w i t h 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) w i t h ? . u n i l a t e r a l thumb Polydactyly and two cases w i t h ? p o s t a x i a l Polydactyly.  Whether there  could be a family h i s t o r y f o r supernumerary d i g i t s i n the l a t t e r two cases was not i n d i c a t e d .  Radial d u p l i c a t i o n appears to be the most common type of Poly-  d a c t y l y i n trisomy 21 syndrome; the a s s o c i a t i o n i s probably not c o i n c i d e n t a l since the frequency of t h i s type of d u p l i c a t i o n i s higher i n the mongol populat i o n , 2.1 per 1,000 (Pabia & D r o l e t t e , 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 f i g u r e s from f i v e studies (Hecht et a l . , 1963; Smith,  1964; Taylor & Moores, 1967; Taylor,• 1968; Benady & H a r r i s , 1969), incidence can be estimated at 0.17. per 1,000 newborns or 1 per 6,040.  Findings i n  p a t i e n t s w i t h a t r i s o m i c E complement are presented i n Table XXVII. P o l y d a c t y l y i s not c h a r a c t e r i s t i c  of the syndrome but i t does occur.  Among  87 cases from the l i t e r a t u r e (references f o r 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 r e n a l anomaly cryptorchidism l i m i t e d h i p abduction abnormal thumbs f l e x i o n deformities of f i n g e r s overlapping f i n g e r s short and/or d o r s i f l e x e d b i g toe prominent calcaneus Source:  Smith et a l , 1960; Lewis, 1964; Taylor, 1968  106 and an a d d i t i o n a l 13 from the f i l e s of U.B.C, D i v i s i o n of Medical f i v e cases were reported to have supernumerary f i n g e r s .  Genetics,  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 t h i s case  has not been included i n the t a b u l a t i o n 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 f i n g e r s , i n the others the extra d i g i t s may have been w e l l formed. Although the border of the hand was s p e c i f i e d 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 f i n g e r ( l / l O O ) , broad or large f i r s t toes  (4/1OO)  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 a d d i t i o n to the more common anomalies of the e x t r e m i t i e s , also e f f e c t s a range of d i g i t a l reduction and d u p l i c a t i o n somewhat s i m i l a r ' t o that seen i n the polydactyly/imperforate  anus/vertebral anomalies syndrome with abnormal  development of the p o s t a x i a l or the p r e a x i a l borders, more commonly of the hands than of the f e e t .  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.  D e t a i l s 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) w i t h e i t h e r t r a n s l o c a t i o n or isochromosome and 13 ('5.9 %) with trisomy/normal mosaicism.  Based  on p h y s i c a l f i n d i n g s the syndrome has been reported i n a d d i t i o n a l patients who have not had chromosome i n v e s t i g a t i o n s or whose karyotype appeared to be e i t h e r 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). equal w i t h only a s l i g h t excess of females: (Magenis et a l . , 1968). are  The sex r a t i o i s approximately  male to female r a t i o of 0.92  P h y s i c a l f i n d i n g s most frequently seen i n the syndrome  l i s t e d i n Table XXVIII. • D e t a i l s on the d i g i t a l anomalies have been compiled f o r 101 cases which are  tabulated i n Appendix C and come mainly from the l i t e r a t u r e . table are probands numbers 43, 46 and 70.  Included i n the  No attempt has been made to d i f f e r e n -  t i a t e between cases w i t h seven D chromosomes, t r a n s l o c a t i o n 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 f i n g e r s , hyperconvex f i n g e r n a i l s , broad and/or long f i r s t toes, angulated or d o r s i f l e x e d f i r s t toes, hypoplastic t o e n a i l s , syndactyly and Polydactyly. Pew cases were reported to have normal e x t r e m i t i e s . The p r e a x i a l anomaly of the hands which was c o n s i s t e n t l y noted i s r e t r o f l e x i b l e thumbs.  In the s e r i e s of p a t i e n t s of Table XXVIII t h i s was noted i n  17 out of 42 c h i l d r e n (40 fo).  Abnormal development of the p r e a x i a l border of  the feet was l e s s frequently reported (16/101 p a t i e n t s , 16 fo) and included P o l y d a c t y l y ( 3 ) and extremely broad and/or long f i r s t toes ( 8 ) , and d o r s i f l e x i o n (6).  Ten of the 16 cases w i t h abnormal f i r s t toes also had p o s t a x i a l Polydactyly. P o l y d a c t y l y was present i n 71 out of 101 cases (see Table XXIX).  Because  d u p l i c a t i o n i s predominantly p o s t a x i a l i n the D| trisomy syndrome, i f a case d e s c r i p t i o n f a i l e d to s p e c i f y the border a f f e c t e d , i t was assumed to be u l n a r and/or f i b u l a r . . The hands alone (29) or the hands and feet ( 2 4 ) are most often a f f e c t e d . 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 f o o t .  D u p l i c a t i o n 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 s l o p i n g forehead  25/36  holoprosencephaly type defect with varying degrees of incomplete development of f o r e b r a i n and o l f a c t o r y and o p t i c nerves  23/31  defects i n c r a n i o f a c i a l development from hypot e l o r i s m to cebocephaly and c y c l o p i a  35/41  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 o r hearing l o s s  19/29  c a p i l l a r y hemangiomata, often of forehead  24/39  s o f t t i s s u e defects w i t h redundant f o l d s i n the mandibular and p e r i o r b i t a l regions  11/15  Polydactyly, o c c a s i o n a l l y 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 f i n g e r s  21/32  hyperconvex f i n g e r n a i l s  28/38  p o s t e r i o r prominence of heel  20/43  cardiac abnormality: dextro-position...  31/42  i n c l u d i n g VSD, P M , ASD,  malformed r i b s w i t h asymmetry of bony thorax  6/ 8  r e n a l anomalies  11/18  u m b i l i c a l or i n g u i n a l hernia, abdominal w a l l abnormalities  20/43  cryptorchidism, abnormal scrotum i n males  17/20  bicornuate or biseptate uterus, ovarian abnormalities i n females  11/12  Source:  Snodgrass et a l . , 1966; Taylor, 1968; James et a l . , 1969; Taylor et a l . , 1970.  109 Table XXIX.  S i t e of Polydactyly i n Trisomy D, Syndrome  No. of cases L ulnar  9  R ulnar  3  B ulnar  17 •total  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 total  24  L fibular  2  B fibular  2  B fibular, L tibial  1  L fibular, B t i b i a l  1  B tibial  . total  extremity unknown  Source:  1 7 11  total  11  total  71  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 f i n g e r i n s e r t e d between the t h i r d and f o u r t h d i g i t s and a postminimus, and f o r the f o u r t h there was no f u r t h e r desc 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 e x h i b i t p o s t a x i a l Polydactyly as w e l l , makes i t necessary -to consider that trisomy of a D or.part.of a D chromosome e f f e c t s or contributes to d u p l i c a t i o n of both borders of the e x t r e m i t i e s .  V a r i a b i l i t y i n expression  of  d i g i t a l d u p l i c a t i o n 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 a f f e c t 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 b r a i n ( 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  s e v e r i t y ; most frequently there i s a c e n t r a l diamond-shaped palpebral f i s s u r e with"a s i n g l e globe manifesting various degrees of doubling of the i n t r i n s i c s t r u c t u r e s " ( G o r l i n & Pindborg, 1964,  p. 179).  Often a p r o b o s c i s - l i k e  appendage representing the nose i s located above the eye on the lower part of the forehead (Sedano & G o r l i n , 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. gave a prevalence f i g u r e of 0.06  per 1,000  M i t a n i (1954)  f o r c y c l o p i a and cebocephaly  among i n f a n t s whereas these anomalies were as frequent as 6.2 per 1,000 embryos of 5.5 - 30 mm CRL  (Mshimura, 1970).  among  Sarma (1963) found c y c l o p i a  was often associated with high p a r i t y and hydramnios. Cyclopia i s not e x c l u s i v e l y an i s o l a t e d defect.  An a s s o c i a t i o n with  Polydactyly i s w e l l documented i n the l i t e r a t u r e and has occurred i n approximately 6 fo of the cases described.  Although supernumerary d i g i t s are the  most common s k e l e t a l anomaly seen with c y c l o p i a (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 t r i s o m i c D complement i n c y c l o p i c (Toews &  Jones, 1968) and cebocephalic i n f a n t s (McKusick, 1961; Buhler et a l . , 1962) confirmed  the s u s p i c i o n that these malformations are extremes i n the range of  abnormal prosencephalon cleavage of trisomy  syndrome.  Undoubtedly some of  the previous reports o f i n f a n t s w i t h c y c l o p i a and p o s t a x i a l Polydactyly were cases of  trisomy.  However, perhaps not a l l cases with p o s t a x i a l d u p l i c a t i o n  r e s u l t from the presence of an extra D chromosome.  Supernumerary d i g i t s of the  ulnar border o r 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 f i n g e r s on both \ hands. The Polydactyly seen w i t h c y c l o p i a i s . not l i m i t e d to the p o s t a x i a l border and several i n f a n t s with thumb Polydactyly have been described.  Radial dupli-  c a t i o n occurs l e s s frequently than p o s t a x i a l (Sedano & G o r l i n , 1963).  An idea  of the r e l a t i v e frequency i s given by P o t t e r (1952) who found among 15 i n f a n t s with some degree of c y c l o p i a or cebocephaly, s i x w i t h b i l a t e r a l accessory ulnar d i g i t s and one w i t h d u p l i c a t i o n of the thumbs.  One newborn described as having  a c y c l o p i a type defect and u n i l a t e r a l Polydactyly of the r i g h t thumb was ascertained 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 i n f a n t s . The e t i o l o g y of cases with thumb Polydactyly most l i k e l y d i f f e r s from at l e a s t a proportion of the cases with p o s t a x i a l Polydactyly since r a d i a l d u p l i c a t i o n i s not known to occur with  trisomy.  been found i n f f o u r cases of c y c l o p i a :  Other chromosomal errors have  two with d e l e t i o n or p a r t i a l d e l e t i o n  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 f o u r t h i n f a n t with an abnormal karyotype who was postulated to have d e l e t i o n of a "small chromosome segment" and whose f a m i l y h i s t o r y includes three other  112 Table XXX.  Cases of Polydactyly Associated with Cyclopia  No. of cases  Sex  Type of Polydactyly and a d d i t i o n a l anomalies when given  Durlacher (1915)  1  M  L ulnar, L f i b u l a r Polydactyly  Boyd and M i l l e s (1951)  1  F  R postminimus, small scar at corresponding p o s i t i o n L hand  .1  F  B ulnar and f i b u l a r Polydactyly, accessory d i g i t s well-formed; bicornuate uterus  P o t t e r (1952)  6  -  B ulnar Polydactyly  Sarma (1963) '  1  M  B u l n a r , R f i b u l a r Polydactyly  Sarma (1963) .  1  F  R ulnar Polydactyly  Sedano and G o r l i n (1963)  1  F  R postminimus, L accessory well-formed  P o t t e r (1952)  1  C a r l i and Torre (1961)  1  F  R r a d i a l Polydactyly, terminal phalanx reduplicated; p r e a u r i c u l a r appendage L  Sarma (1963)  1  F  R thumb b i f i d ; anencephaly  B.C.  1  F  R r a d i a l Polydactyly (see case d e s c r i p t i o n , Appendix A)  Chapman (1936)  1  M  L hand w i t h s i x f i n g e r s ; hypop l a s t i c genitalia'  Sarma (1963)  1  F  s i x d i g i t s on each hand  P f i t z e r and Muntefering (1968)  1  -  Polydactyly, border unknown (one of four r e l a t e d i n d i v i d u a l s with cyclopia)  Reference  Rysanek (i960)  Note:  study, proband no. 14  toe,  B r a d i a l Polydactyly  In a d d i t i o n the cases of E l l i s (1866) and Ploucquet ( c i t e d 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 r e s u l t from more than one abnormal  c o n d i t i o n which a f f e c t s the e a r l y development of the embryo.  Polydactyly/imperforate anus/vertebral anomalies syndrome. and Gerald described ten patients with a polydactyly/imperforate b r a l anomalies [P/IA/VA] syndrome.  In 1968  Say  anus/verte-  Since that o r i g i n a l report, 19 a d d i t i o n a l  p a t i e n t s have been described w i t h s i m i l a r features and a number of accounts of imperforate anus i n a s s o c i a t i o n with d i g i t a l and a d d i t i o n a l 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 c o n s i s t of reduction defects rather than the P o l y d a c t y l y or combination of Polydactyly and hypoplasia observed i n the f i r s t ten cases.  In a d d i t i o n Stevenson et a l . (1966) l i s t a case with  imperforate anus, tracheo-oesophageal f i s t u l a , v e r t e b r a l and r i b anomalies, but which isnnot noted to have malformed e x t r e m i t i e s . To eliminate the i m p l i c a t i o n that Polydactyly i s c o n s i s t e n t l y 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 f r e q u e n t l y v e r t e b r a l anomalies, also abnormalities of the  u r i n a r y t r a c t i n c l u d i n g r e n a l agenesis, g e n i t a l anomalies, malformations of the lower limbs and of the thumbs. As f a r as i s known, f a m i l i e s of the patients are not r e l a t e d except f o r the f a t h e r and four c h i l d r e n 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 f o r cases w i t h Polydactyly i n B.C.  gives an estimated incidence of 2.0 per 100,000  114 l i v e born i n f a n t s . 0.007 to 0.05  Say et a l . (1971) estimate the incidence to be between .  per 1,000  l i v e b o r n Caucasian i n f a n t s .  p a t i e n t s i s 24 males : 13 females : 12 unknown.  The sex r a t i o of the  I t w i l l be i n t e r e s t i n g to  see whether t h i s 2 : 1 sex r a t i o i s maintained as a d d i t i o n a l cases are  reported.  F i v e out of ten i n f a n t s died before the age of ten months and the prognosis another c h i l d of t h i s group of ten i s reported to be poor.  for  Chromosome studies  have been done on two patients and both had a normal karyotype.  Principal  f i n d i n g s i n 49 p o s s i b l e cases are presented i n Table XXXI. There are 36 patients with a p r e a x i a l d i g i t a l defect and s i x with posta x i a l Polydactyly (see Table XXXII).  Usually one thumb i s a f f e c t e d .  Including  the group with t r i p h a l a n g e a l d u p l i c a t i o n , 32 patients have Polydactyly and have rudimentary or absent d i g i t s .  ten  Three or p o s s i b l y four i n d i v i d u a l s present  both reduction and d u p l i c a t i o n of d i g i t s and are included i n both groups.  This  sample has been biased i n ascertainment of c h i l d r e n with d u p l i c a t i o n since 12 p a t i e n t s were found through studies on Polydactyly.  Of the 14 c h i l d r e n 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 p r e a x i a l Polydactyly or t r i p h a l a n g e a l thumbs i n t h e i r nine cases.  I t would appear therefore that reduction deformities are  l e s s 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 s e n s i t i v e period of the pregnancy present p r e a x i a l defects ranging from a p l a s i a to d u p l i c a t i o n as do c h i l d r e n with syndromes believed to r e s u l t from mutant genes (acrocephalopolysyndactyly, syndrome and Fanconi's panmyelopathy).  Holt-Oram  The p r e a x i a l anomalies of three of the  l u x o i d mutants i n the mouse range from o l i g o d a c t y l y to Polydactyly and one  of  115 Table XXXI.  C l i n i c a l Features of the Polydactyly/imperforate Anus/ V e r t e b r a l Anomalies Syndrome Wo. of cases  d i g i t a l anomalies: p r e a x i a l d u p l i c a t i o n or reduction, o c c a s i o n a l l y p o s t a x i a l Polydactyly  48/49  imperforate anus: may be i n combination w i t h recto-perineal f i s t u l a  49/49  v e r t e b r a l anomalies: i n c l u d i n g increased or decreased no. of vertebrae, s c o l i o s i s , b i f i d vertebrae, hemivertebrae, fused v e r t e b r a l bodies  17  r i b anomalies: i n c l u d i n g increased or decreased number of r i b s , hypoplasia, fusions  12  f a c i a l asymmetry  2  congenital heart defect  5  c l e f t l i p and/or palate  2  tracheo-oesophageal f i s t u l a and/or oesophageal a t r e s i a  7  lung abnormality  2  hypoplasia of ileum  4  a p l a s i a of spleen  "  u n i l a t e r a l a p l a s i a of kidney i n g u i n a l hernia5'  1 5  ,  2  omphalocele  1  cryptorchidism  2  congenital d i s l o c a t i o n of the h i p  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  (? 6)  116  Table XXXII.  D i g i t a l Anomalies of the Polydactyly/imperforate Anus/ V e r t e b r a l Anomalies Syndrome  D i g i t a l anomaly  Number of cases  Number of cases r a d i a l Polydactyly  t r i p h a l a n g e a l thumbs, may be b i f i d  7  U r a d i a l Polydactyly r a d i a l hypoplasia 2  10 + ? 2  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.  2 1*  U rudimentary thumb B t i b i a l polyd. & R r a d i a l polyd.*  1  R t i b i a l polyd. & L r a d i a l hypop.  1  L t i b i a l Polydactyly  1  2  B radial aplasia  3  U radial aplasia  1  R rudimentary thumb & L r a d i a l abhorm.  1  U r a d i a l abnormality  1  B absence of radius  1  p o s t a x i a l polyd. 1  B ulnar Polydactyly  4  B ulnar & B f i b u l a r Polydactyly  1  B f i b u l a r Polydactyly  oligodactyly 1  Source:  t i b i a l Polydactyly  radial  abnormality  Polydactyly  border unknown  see Appendix C  117 these mutants; dominant hemimelia, also involves defects of the v i s c e r a  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 p r e a x i a l border. To f i n d i n the P/lA/VA syndrome that d i g i t a l anomalies can be e i t h e r exclus i v e l y p o s t a x i a l or p r e a x i a l (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 extremi t i e s ranging from a p l a s i a to d u p l i c a t i o n , as w e l l as the n o n - d i g i t a l anomalies of the syndrome, r e s u 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 e x i s t s  that the e t i o l o g y of cases with p o s t a x i a l d u p l i c a t i o n i s d i f f e r e n t from that of cases with p r e a x i a l defects as appears to be true i n the a s s o c i a t i o n of c y c l o p i a with Polydactyly  (see p.  111).  In one family (Townes & Brocks, 1970)  the father and four of h i s s i x  c h i l d r e n have imperforate anus and t r i p h a l a n g e a l thumbs, which i n some cases are b i f i d .  At the present time i t seems most reasonable to include these  i n d i v i d u a l s among cases of the polydactyly/imperforate syndrome.  Inheritance  anus/vertebral anomalies.,  would appear to be autosomal dominant i n t h i s family.  In the f a m i l i e s of two a d d i t i o n a l patients another family member with d i g i t a l defect but without other signs of the syndrome has d u p l i c a t i o n of the same border of the limbs as the p a t i e n t .  In one family (number 124, B.C.  study)  i t i s the p o s t a x i a l border a f f e c t e d ; i n the other (Puhrmann, 1968), the prea 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 p r e d i s p o s i t i o n f o r d i g i t a l defect of a given border and contributes  to the p r e d i s p o s i t i o n .  Or there may  be  v a r i a b l e e x p r e s s i v i t y of the P/lA/VA syndrome, i n which case, i n c l u d i n g a s i b with imperforate anus (Puhrmann, 1968),' there would be three i n d i v i d u a l s i n the two f a m i l i e s who  present with a forme f r u s t e .  The l a t t e r i n t e r p r e t a t i o n  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 f a c t that u n i l a t e r a l Polydactyly of a biphalangeal  thumb i s r a 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 c o r r e c t l y be c a l 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 c h a r a c t e r i s t i c s 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 f i g u r e s are based on over 300 cases.  Ammann found 45.6 fo of the patients i n h i s study  presented with a l l of the f i v e c h a r a c t e r i s t i c s and thus e x h i b i t e d a complete form of the syndrome. however.  D e f i n i t i o n of what c o n s t i t u t e s a complete form v a r i e s  Stiggelbout (1969) considers a p a t i e n t who e x h i b i t s the majority of  signs and i n whose s i b s h i p the missing signs occur also to be an example of the f u l l syndrome.  Not i n f r e q u e n t l y , a d d i t i o n a l f a m i l y emembers w i l l e x h i b i t  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 p a t i e n t s w i t h 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 or brachydactyly. the r i g h t .  f)  there was i s o l a t e d syndactyly  D u p l i c a t i o n a f f e c t e d the l e f t extremities equally often .as  When of the hands i t might be a f l e s h y p e d i c l e , whereas supernum-  erary toes were more common and were u s u a l l y w e l l developed. not e x c l u s i v e l y p o s t a x i a l .  Duplication i s  Occasionally the supernumerary d i g i t may involve  abnormal development of the thumbs or index f i n g e r s ( B e l l , 1958). 38 patients i n Ammann's study had a b i f i d thumb.  Two of the  Of these two p a t i e n t s , one  a l s o had b i l a t e r a l f i b u l a r P o l y d a c t y l y and was probably a f f e c t e d with the syndrome; the second p a t i e n t was a t y p i c a l of the syndrome i n other  respects  i n a d d i t i o n to the p r e a x i a l ' d u p l i c a t i o n . 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. Part A:  C l i n i c a l Features of the Laurence-Moon-Biedl Syndrome Frequency by sex of the f i v e p r i n c i p a l anomalies males  females  total  obesity  26/28  20/20  46/48  t a p e t o - r e t i n a l degeneration  24/28  20/20  44/48  anomalies of the extremities: poly-, syn-, & brachydactyly  23/28  17/20  40/48  mental defect  24/28  14/20  38/48  hypogenitalism  24/28  9/20  33/48  Part B: A d d i t i o n a l anomalies*  Wo. of cases  progressive l a b y r i n t h i n e deafness  5  r e n a l defect  . 5  diabetis mellitus  5  c r a n i a l dysostosis disorders of basal metabolism  11 •  9  * f o r f u r t h e r d e t a i l s see Ammann, 1970 or Stiggelbout, 1969 Part C:  S i t e of Polydactyly  Wo. of cases  both hands and both feet  10  one hand and both feet both hands  5 .  1  one hand  3  both feet  6  one foot  5  r i g h t hand and r i g h t foot  1  l e f t hand and l e f t foot  1  l e f t hand and r i g h t foot  1  extremity involved unknown  5 38  Source:  Ammann, 1970  120 frequency of P o l y d a c t y l y among a f f e c t e d males and a f f e c t e d 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, e s p e c i a l l y a c h a r a c t e r i s t i c form of i s o l a t e d brachydactyly which Ammann suggests i s of equivalent importance as the presence of Polydactyly or syndactyly. I n the past, i t may have been f a i l u r e to detect e x 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 characte r i s t i c most frequently nonpenetrant. In the B.C. study one proband (number 131) and h i s s i b presented the LMB syndrome.  Correcting f o r the frequency of Polydactyly among a f f e c t e d i n d i v i -  duals, t h i s suggests an incidence of approximately 0.9 per 100,000 l i v e b o r n i n f a n t s over 1964 - 1967.  The complex of anomalies i n the syndrome appears to  be i n h e r i t e d i n an autosomal recessive manner.  The primary defect and i t s con-  comitant e f f e c t s upon embryogenesis have not been determined.  The f a c t that  the toe anlagen of the f i b u l a r border are formed a t a l a t e r stage than f i n g e r anlagen may be s i g n i f i c a n t i n e x p l a i n i n g why the feet of i n d i v i d u a l s with the syndrome are more commonly and more severely a f f e c t e d by Polydactyly and synd a c t y l y than the hands (Stiggelbout, 1969).  Smith-Lemli-Opitz syndrome.  Three unrelated p a t i e n t s w i t h m u l t i p l e con-  g e n i t a l 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 s i m i l a r cases followed and a t l e a s t 31 patients have been  described w i t h Smith-Lemli-Opitz [aSLO]' syndrome (20 males and 11 females). In f i v e s i b s h i p s , p o s s i b l y s i x , there have been more than one a f f e c t e d i n d i v i dual and i n two of these f a m i l i e s 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 i n h e r i t a n c e .  The incidence of the syndrome i s unknown.  There  are three cases (numbers 38, 66, 117) i n the B.C. study, however since Polyd a c t y l y i s not a c a r d i n a l feature the incidence of 0.02 or approximately 4,500 l i v e b o r n i n f a n t s found i n t h i s study i s undoubtedly low.  1 per  Clinical  f i n d i n g s i n p a t i e n t s with t h i s syndrome are l i s t e d i n Table XXXIV. In a d d i t i o n to syndactyly ( u s u a l l y of the second and t h i r d toes) and f l e x i o n of the f i n g e r s , o c c a s i o n a l l y Polydactyly and reduction deformities of d i g i t s have been reported (14/31). cases.  Table XXXV presents d e t a i l s noted i n 12  Supernumerary d i g i t s present i n eight cases are most l i k e l y p o s t a x i a l .  Two of these cases were also noted to have somewhat rudimentary thumbs, a feature found i n s i x a d d i t i o n a l cases as w e l l .  R a d i a l reduction defects and  ulnar P o l y d a c t y l y i s also seen i n the trisomy 17-18 syndrome.  I t i s interesting  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 r a i s e s the p o s s i b i l i t y that  d u p l i c a t i o n as w e l l as reduction of the thumb may be seen i n the Smith-LemliOpitz syndrome.  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. Three male s i b s with 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 P o l y d a c t y l y were reported by Simoupolis w i t h i n minutes a f t e r i b i r t h .  et a l . (1967).  These i n f a n t s died  Chromosomal studies of the parents and t h e i r t h i r d  a f f e c t e d i n f a n t revealed a normal karyotype, and the parents were not known to be r e l a t e d . A s t r i k i n g resemblance between these cases and proband number 73' and her s i b has been noted (Lowry, 1971).  These c h i l d r e n presented  ulnar  Polydactyly, p o l y c y s t i c kidneys and i n t e r n a l hydrocephalus (see case descriptions i n Appendix A ) . The second c h i l d died s h o r t l y a f t e r 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 e i t h e r of t h e i r f a m i l i e s .  122  T a b l e XXXIV.  C l i n i c a l Features  o f the S m i t h - L e m l i - O p i t z Syndrome  No. o f cases f a i l u r e to t h r i v e  25/25  hypotonicity  10/23  hypertonicity  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 r i d g e s  18/21  high  13/22  palate defect  21/22  s h o r t neck  14/14  flexed fingers  11/15  ear  6/26  Polydactyly . simian or bridged pedal  syndactyly  simian  crease  19/23 24/28  abnormal f e e t  16/22  hypospadias  11/18  cryptorchidism  13/18  scrotum abnormal  11/1 6  normal chromosomes  13/13  Source:  Lowry e t a l . , 1968; Park e t a l . , 1968; Ruvalcaba e t a l . , 1968; D a l l a i r e , 1969; F i n l e y e t a l . , 1969; H a n i s s i a n & Summitt, 1969; S i n c l a i r e t a l . , 1969  123 Table XXXV.  D i g i t a l Anomalies of the Smith-Lemli-Opitz Syndrome  Reference  Sex  D e s c r i p t i o n of d i g i t a l anomaly  Smith et a-L (1964)  M  s k i n tag L ulnar  Kenis & Hustinx  (1967)  F  6th f i n g e r L hand, postminimus o f f prox. phal. R hand; B short thumbs  (1967)  M  s k i n tag o f f middle phalanx 5th f i n g e r R; short t h i r d f i n g e r B ?  Lowry et a l . (1968) (B.C. study, case no. 66)  F  extra d i g i t B ulnar  D a l l a i r e (1969)  F  D a l l a i r e (1969)  M  extra d i g i t o f f prox. phal. 5th toes B, uniphalangeal thumb B  B. C. study, case no. 38  M  extra d i g i t R ulnar  B. C. study, case no. 117  M  extra d i g i t s B ulnar, L f i b u l a r  Pinsky & DiGeorge (1965)  F  "stuck on" appearance of thumb & small thenar eminence B, small f i r s t metacarpal B; small prox. phalanx great toe B  Fine et a l . (1968)  M  hypoplastic lowset thumb B  Ruvalcaba et a l . (1968)  M  R thumb hypoplastic, f l a t thenar eminence B; f u s i o n 4th and 5th metacarpals  B l a i r & Martin (1966)  F  short thumb B  Park et a l . (1968)  M  short thumb B  F i n l e y et a l . (1969)  F  short h a l l u x B  /  Kenis & Hustinx  " extra biphalangeal d i g i t R ? ulnar  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 . anomalies.  This f i g u r e includes i n f a n t s with m u l t i p l e congenital  Incidence was highest i n 1966 (1.35), apparently due to a  greater number of ulnar cases. Parental age f o r the e n t i r e cohort i s s i m i l a r to 1964 - 1967 c o n t r o l f i g u r e s f o r the province.  However among ulnar cases unassociated  with  m u l t i p l e congenital anomalies mean maternal and paternal age appears to • be higher f o r female probands than f o r male.  Wo d i f f e r e n c e was detected  between p a r i t y of mothers of male probands compared to female probands or compared to B.C. mothers of l i v e b o r n i n f a n t s i n 1964 - 1967. Based on cases without m u l t i p l e congenital anomalies, s p e c i f i c types of Polydactyly were found to have the f o l l o w i n g incidences:  r a d i a l , 0.20;  t i b i a l , 0.04; polysyndactyly, 0.01; u l n a r , 0.32; f i b u l a r , 0.16; and u l n a r f i b u l a r , 0.09. R a d i a l d u p l i c a t i o n 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 d u p l i c a t i o n 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 f i n g e r s are nearly always located on the l e f t hand.  F i b u l a r 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 d u p l i c a t i o n are u s u a l l y b i l a t e r a l on the upper and lower limbs.  Extent of d u p l i c a t i o n i s quite  v a r i a b l e i n p r e a x i a l Polydactyly and may be t r i p h a l a n g e a l .  Among p o s t a x i a l  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 r a r e l y pedicular, often syndactylous.  When both  ulnar and f i b u l a r Polydactyly are present the duplicated elements are u s u a l l y well-formed. Genetic h i s t o r i e s i n d i c a t e i n 32 f a m i l i e s out of 138 there i s another i n d i v i d u a l w i t h Polydactyly.  F o r , s p e c i f i c types of Polydactyly the f o l l o w -  ing proportion of cases without m u l t i p l e congenital anomalies had a p o s i tive family history:  r a d i a l , 5 - 19  t i b i a l , 0 fo; u l n a r , 29 %; f i b u l a r ,  125  25 f; and u l n a r - f i b u l a r , 73 f.  Transmittance  of p o s t a x i a l Polydactyly by  unaffected parents w i t h a h i s t o r y of accessory d i g i t s i s more common among females, and more common f o r ulnar and f i b u l a r types of Polydactyly. Nonpenetrance of gene.('s) f o r u l n a r - f i b u l a r Polydactyly i s unknown among males. Polygenic i n h e r i t a n c e of ulnar and of f i b u l a r types of Polydactyly i s suggested by the f i n d i n g that the percentage of a f f e c t e d s i b s i s greater when there i s a h i s t o r y of Polydactyly i n previous generations 6.6 fo) than f o r probands with a negative h i s t o r y ( 1 . 2 fo).  (approximately.  The number of  a f f e c t e d s i b s of the probands ( 3 / 1 0 7 ) i s i n agreement with the number which would be expected f o r a polygenic t r a i t .  Data f o r u l n a r - f i b u l a r Polydactyly  i s more ccompatible with dominant i n h e r i t a n c e w i t h reduced penetrance among females.  F i f t y percent of the o f f s p r i n g of polydactylous males were a f f e c t e d ;  a smaller percentage of the c h i l d r e n of a f f e c t e d mothers were polydactylous. Among u l n a r - f i b u l a r cases w i t h no h i s t o r y of accessory d i g i t s i n previous generations, 17.4 f of the s i b s were polydactylous. The occurence of minor anomaly or a s i n g l e major anomaly among polydactylous i n f a n t s does not appear to be much greater than would be seen among i n f a n t s w i t h a given minor anomaly. more frequent.  However m u l t i p l e major anomalies are 25 times  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 a d d i t i o n a l major anomalies than a c h i l d w i t h one major anomaly who has the normal number of d i g i t s .  M u l t i p l e congenital  anomalies were most commonly seen w i t h u l n a r - f i b u l a r Polydactyly, and 60 fo of the c h i l d r e n w i t h more completely formed accessory d i g i t s of t h i s type had m u l t i p l e malformations.  This may r e f l e c t the f a c t that u l n a r - f i b u l a r  d u p l i c a t i o n i s the type most commonly seen as a feature of various syndromes.  126 Literature Cited A a s e , J . M., and S m i t h , D. ¥. 1969. C o n g e n i t a l anemia and t r i p h a l a n g e a l thumbs: a new syndrome. J . P e d i a t . 74:471-4. A h l . f e l d 1880. M i s s b i l d u n g e n L e w i s , 1909.) Albrecht  des Mensehen  P. 106. L e i p z i g .  1886. C e n t r a b l . f . 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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 t r i p l o - X . J . Pediat. 60:498-502. U l l r i c h , 0. 1951. X. Der Status Bonnevie-Ullrich im Rahmen anderer "DyscranioDysphalangien". Erg. inn Med., Neue Polge 2:456-8. 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. 93rd Report f o r the year 1964. Issued by the Dept. of Health Services and Hospital Insurance. B r i t i s h Columbia: A. Sutton, 1966. 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. 94th Report f o r the year 1965. Issued by the Dept. of Health Services and Hospital Insurance. B r i t i s h Columbia: A. Sutton, 1967. 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(Cited by Nishimura, 1970.)  J . Jap. Obstet. Gyneo.  Temtamy, S., and McKusick, V. A. 1969. Synopsis of hand malformations with p a r t i c u l a r emphasis on genetic f a c t o r s . In Conference pn the C l i n i c a l Delineation of B i r t h Defects, 1st, Baltimore, 1968. B i r t h defects: o r i g i n a l a r t i c l e series, ed. D. Bergsma, v o l . 5, pt. 3, Limb Malformations, pp. 125-84. New York: The National Foundation. Wood, V. E. 1970. Duplication of the index finger.  52:569-73. ,  J . Bone Joint Surg. (Amer.)  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 l a s t column of the r i g h t page. are  grouped according to the affected border of the limb(s):  Probands radial  duplication, cases 1 - 31; t i b i a l duplication, cases 32 - 37, ulnar duplication, cases 3 8 - 9 1 , f i b u l a r duplication, case's 92 - 115; ulnar and f i b u l a r duplication, cases 116 - 131; and s i t e of duplication unknown, cases 1>32 - 138.  2.  A question mark i n the t h i r d column regarding s i t e of duplication indicates examination of the d i g i t s or information from medical records or the family suggested the i n d i v i d u a l had Polydactyly but this could not be confirmed.  3.  The following probands are known to have anomalies i n addition to Polydactyly.  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) V i c t o r i a , (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:  D.  Powell River  (a) Haney, (b) Langley, (c) Mission, (d) Chilliwack  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  5.  J.  Kimberley  K.  Williams Lake and Alexis Creek  L.  Prince George  M.  Burns Lake  N.  Skeena River. Area:  0.  Peace River Area:  (a) Prince Rupert, (b) Terrace, (c) Kitimat (a) Fort St. John, (b) Dawson Creek  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 f o r maternal or paternal age indicates conf l i c t i n g data from d i f f e r e n t sources or the exact birthdate unknown.  7.  Sources of information were interviews with the families by Daryl C. Jones (DCJ), by James R. M i l l e r , Ph.D.  (JRM) and R. Brian Lowry, M.D.  (RBL),  D i v i s i o n 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 8.  with family physicians.  In cases where the pedigree was not taken i n an interview with the fami 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 h a l f sibs t h i s i s  U-5 indicated, however no d i s t i n c t i o n .is made between legitimate and i l l e g i t imate progeny.  •  Symbols used i n the pedigrees are the following: 1 2 3 male ( i ), female ( i ) and i n d i v i d u a l of unknown sex (I ) with Polydactyly  0  presence of Polydactyly  /  suspected  slanting arrow indicates proband v e r t i c a l arrow indicates i n d i v i d u a l has a family h i s t o r y of Polydactyly deceased  1  9.  miscarriage  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  fib  fibular  syndr  syndrome  hypop  hypoplastic  tib  tibial  L  left  U  unilateral  lat  lateral.  uln  ulnar  metatarsal (-carpal) phalangeal  vestig  vestigial  ¥ D  well developed  MP  (joint)  Proband P o s i t i o n number pedigree 1  11^ II  D  e  s  c  r  i  p  t  i  o  n  o f  s  #  d i  i t s  Additional anomalies  R radial c r i b death, age 6 mo.  4  R radial  II  L radial  II  R radial  shaped l i k e a thumb rather than a skin tag  II  convulsions; f a i l u r e to thrive; hypospadias; L t e s t i c l e i n inguinal canal  II  II  II  8  rather large dolichocephalic head; c l e f t l i p and palate; malf. ear R with preauricular append; warty append. L zygoma; f l e x i o n contractures of fingers (?); g e n i t a l i a hypop with defect i n midl i n e of scrotum suggestive of a c l e f t ; imperforate anus; urachus attached to bladder; sex chroma t i n negative  11  L radial  extra thumb  L radial  projects l a t e r a l l y from metac, no bony fusion with shaft of main d i g i t (?)  R radial  thumb loosely hanging by skin below main d i g i t  R radial  n a i l present, no bone palpable  Down's syndrome: floppy body tone; large tongue; f o l d of skin at nape of neck; CRD (?); wide space between toes 1 and 2  hemangioma of upper l i p and nose  147 B i r t h Ethnic Mat. Pat. Source ,,, , _ , , „ . . . or„ Birthdate Proband Sex place o r i g i n age age inform. lb  NInd  24  (30) MRec DCJ  14 Nov 64  DMV  P  H  NInd  31  36  MRec DCJ  28 May 64  H¥V  M  Ob  NInd  17  23  MRec DCJ  15 May 64  ES  . M  Aa  NInd  33  38  MRec  17 Jun 66  OTP '  M  _. . Pedigree n  b  +  6 6 6 A.*b*  M  Ind  18 4—  MRec DCJ  24 May 67  HIL  M • o  Ca  Ad^  Ba  NInd  Ind  —  41  43  MRec DCJ  8 Apr 66  MGB  M  17  —  MRec  13 J u l 65  MJDC  M  19  —  MRec  11 Aug 66  GSM  M  Q I•  5 ,  •  •  OT-O  Q  f  _  8  number  in,. pedigree  Description of supern. d i g i t s _ _ _  Additional anomalies  11^  L radial  tied off  10  IV  L radial  about normal thumb s i z e , l a t e r a l at base of main d i g i t , n a i l but no bone  asthma  11  II  L radial  skin tag o f f middle of prox phal, no nail  p i l o n i d a l dimple  12  II  L radial  pedicle, n a i l but no bone  B preauricular appends.  13  II  E radial  prox phal underdeveloped, and short, d i s t a l phal duplic, acces. i s l a t e r a l  p i l o n i d a l sinus  R radial  d i s t a l phal d u p l i c .  arrhinencephaly; no s e l l a t u r c i c a ; multiple defects i n calvafium; assymetric a l misshapen s k u l l with i r r e g . defects of c r a n i a l bones mainly L; anophthalmia; at base of absent nose i s a t r i a n g u l a r shaped defect which connects with a c l e f t i n upper l i p but also extends through the alveol a 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 seve r a l c e r v i c a l vertebrae; hemivertebrae upper dorsal region; abn. R upper r i b s ; g e n i t a l i a small; simian creases B; trigger thumbs B  1.114  Pedigree L  (34) MRec DCJ  11 Jan 67  RT  M  6 J u l 65  SAH  F  MAM  F  8 J u l 67  RS  M  30 Sep 65  BJZ  M  NInd  30  B,d— Nind  17  23  Ba  NInd  39  37 . MRec • 20 Nov 66 DCJ "  Ba  —  21  —  MRec  Bb  —  27  —  MRec  MRec DCJ  D~[—O  6 66  ^  p  S  .  Q  ••  D~f~0 Aa*  —  19  —  MRec  11 Apr 67  MIP  •^resided i n Prince George the f i r s t trimester  F  H  it  Proband P o s i t i o n ^ ... _ m . Description of supern. number pedigree _ _ n  ,. . , digits  Additional anomalies  15  II  L radial  d i s t a l phal d u p l i c .  16  2 II  R radial  d i s t a l phal duplic, a l l e r g y to milk; asthma common prox phal, medial somewhat deviated, l a t e r a l excised abnormal infant, l i v e d 20 minutes; p a r a l y s i s from chest down  II-  17  II  R radial  d i s t a l phal duplic, common prox phal  18  III  L radial  prox phal abn wide, duplic d i s t a l phal, synd to n a i l , n a i l s separate .  I  L radial  L: d u p l i c . d i s t a l phal, synd. nearly to t i p ; R: abnormal d i s t a l placement of thumb  III.  L radial  metac. and prox phal broad, d i s t a l phal duplic, l a t e r a l one ¥ D with a nail,' the medial i s deviated but has an IP j o i n t  ll"'  ? radial  deformed thumb, probably polydactylous, synd. f i n g e r s  20  II  B radial  B prox phal b i f i d , d i s t a l phal d u p l i c .  21  II-  R radial  acces. append, with two small o s s i f i c a t n centers, normally developed n a i l , a t tached near head of metac, no a r t i c u l a t n  19  malf. pinna R; lowset ears; inguinal hernia B; antimongoloid slant to eyes  strabismus  c l e f t palate, b i f i d uvula; convulsions at 14" years of age  151 B i r t h Ethnic Mat. Pat. Source , „ , . _ , . . or_ Birthdate Proband Sex •place o r i g i n age age inform. . Bb  Bd  Wind  Wind  Oa  Ab  Wind  MRec DCJ  9 Nov 65  MRec DCJ  28 Jan 64  CAL  M  26  MRec  22. Mar 65  DRP  M  17  25 - 30  MRec DCJ  30 Aug 66  LFB  P  18  27  17  30  21  GTW  M  MRec  21 Feb 65  JPB  M  Ba  27  MRec  1 Dec 64  JJDM  M  MRec DCJ  22 Jan 64  CEC  F  35  37  O r O T — •  a-r-o  22  Wind  15  5?  Ab  Ba  Pedigree  "b-r-o  19  D-  20  O-i-O  21  16  Proband P o s i t i o n number pedigree  Description of supern. d i g i t s  22  II  ' R radial  ¥ D, two o s s i f i e d phals, n a i l and •' dermal ridges, a t tached near head of metac, no a r t i c u l a t n  23  II  R radial  acces. i s l a t e r a l & somewhat hypop, two phals, the base of prox phal attached to epiphysis of the medial prox phal  24  II  R radial  common metac, l a t . & medial thumbs of approx equal size, biphal, synd at prox phal, overlapping at d i s t a l phal  Additional anomalies high arched palate; malf. pinna and ext. auditory canal L; webbed neck; CRD: VSD, pulmonary valve a t r e s i a with hypop. R ventricle, PDA, profusing pulmonary a r t e r i e s which are hypop, L aortic arch, L descending aorta, R superior vena cava, R i n f e r i o r vena cava; ribs notched R; multiple hemivertebrae upper thoracic region R; b i f i d verteb. lower thoracic region; allergies B vesicoureteral r e f l u x  3  II25  II  B synd f i n g e r s R radial  acces. rud. c a r t i l a g metac and two phals, medially located, p a r t i a l synd of two thumbs  II26  II  feet abnormality, u n t i l age 11 L radial  II  braces  acces. ¥ D, prox phal attached to b i f i d metacarpal  II  27  4-5  microcephalic; meningocele; died age 3T days R radial  acces l a t e r a l with somewhat hypop metac & one phal, joint at lower t h i r d  153 B i r t h Ethnic Mat. Pat. Source Birthdate Proband Sex place o r i g i n age age inform. Be,  Wind  25  34  MRec DCJ  15 Aug 64  GIM  M  Bd  Wind  29  36  MRec DCJ  20 Sep 66  KAW  P  +  Pedigree •-  o-T-a  22  D-T-O  23  5Ti RMD  D-  Ba  Wind  33  33  MRec DCJ  2 Aug 64  Ba  Wind  28  28  MRec DCJ  16 Dec 67  PJS . P  O-r—O  Ga  Chin  28  38  MRec DCJ  25 May 66  HMSW  O-j-O  M  M  24  25  26  6 66 c V i i ti L  Wind  22  25  MRec DCJ  21 Jul. 67  GRB  M  D-T-O  c5~6S~b  27  Proband P o s i t i o n in number pedigree 28  II  29  IT  30  II  31  D e s c r i p t i o n of supern. d i g i t s R radial  R radial (L t r i p h a l )  A d d i t i o n a l anomalies  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 media l l y , slight- deformi t y of the phals R: 2 t r i p h a l thumbs, synd to PIP j o i n t , f u s i o n of two prox phals, l a t e r a l e x c i s . L: t r i p h a l thumb .  R radial  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 b i p h a l & deviated medially  II •  L radial  acces ¥ D t r i p h a l thumb, l a t e r a l , w i t h n a i l , a r t i c u l a t i o n to r e d u p l i c head of metac  32  II  R. t i b i a l  33  II  B tibial  B: p a r t i a l d u p l i c , synd. to n a i l , L b e t t e r developed  34  IT  B tibial  double bones i n t i p of b i g toes  4  3  pinpoint cataract R cataracts reduction deformity of a l l four limbs  II  cataracts 35  II  II  1  R tibial  metat short & t h i c k , prox & d i s t a l phals d u p l i c , toe pointed medially 90° s t i l l b o r n , 28 weeks gestation  155  B i r t h Ethnic Mat. Pat. Source _.. , , _ •, , „ , . . . or _ Birthdate Proband Sex place o r i g i n age age inform. ; Ba  29  —  MRec  15 May 65  KBS  Pedigree  M  28  ?  Ba  Wind  26  Ba  —  32  Be  28  Ba  17  0a  K  MRec PM  25 Apr 67  SJB  P  •n—O  29  MRec DCJ  7 Oct 64  IMQ  M  D-  30  (34) MRec  24 May 66  RPT  M  D-T-O  31  MRec  31 Aug 67  SJER  M  •-  MRec  25 Apr 65  LDB  P  MRec DCJ  9 Mar 67  LMB  F  27  Ba  Wind  Wind  26  19  30  —  29  30  MRec DCJ  '  WC  33  o  /  r O  4 Sep 66  32  -O  M  Ch-r-O  • •  34  Proband P o s i t i o n number pedigree  Description of supern. d i g i t s  Additional anomalies  36  II  B tibial  B: common metat with two a r t i c u l a r faces, l a t e r a l ray better developed, synd. to t i p , separate n a i l s  37  ir  B tibial  R better developed; two d i s t i n c t mobile toes, common metat, biphal, c l e f t to PIP j o i n t ; L synd. to t i p , separate n a i l s , common metat, phals separate  38  II  R ulnar  acces 5th d i g i t  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 f o l d s ; CRD: aortic stenos i s & PDA; anomalous ext. g e n i t a l i a : hypospadias, cryptorchidism, patent urachus; B clubfeet with toe deformities; L hand: wide c l e f t between.2 - 3 fingers; sex chrom. neg.  39  ii-  R ulnar  pedicle o f f deformed 5th f i n g e r , synd of 3 - 4 fingers R  small hematoma; congeni t a l f i s t u l a of the tear*sa!c of L eye  R ulnar  acces t i e d o f f  B ulnar  acces with n a i l & bony tissue  li-  IT ulnar  skin tag  re  B ulnar  ¥ D acces fingers  41  ii-  R ulnar  pedicle o f f 5th at l e v e l of PIP j o i n t  42  II'  R ulnar  acces at base of 5th R hydrocoele of tunica v a g i n a l i s ; b i r t h mark just above umbilicus  40  III II  5  157  B i r t h Ethnic Mat. Pat. Source , . „ , ... or„ Birthdate Proband Sex place o r i g i n age age inform. n  Be  Mind  19  21  (Aa)  n  Pedigree  MRec DCJ  1 Mar 64  RLS  M  o—r-o  36  MRec  1 Jun '65  JEW  M  O-rO  31  Stik V Aa  Nlnd  Be  Ba  Ba  Ba  Nlnd  Nlnd  34  47.  MRec 24 J u l 67 RBL ' DCJ  32  30  MRec DCJ  18  26  30  25  31  JEB  M  2 7 Feb 66  GWJ  M  MRec DCJ  20 Dec 66  ARM  M  MRec DCJ  7 Dec .6.7  MRec  7 Dec 66  O-r-O  On—O—|—•  38  39  740  O-r-O  DEP  AJN  M  M  •nr-O  6 6 i6 /  41  42  Proband Posxtxon m. number pedigree n  43  ^ ... .„ ,. ., Description of supern. d i g i t s _  Additional anomalies  II  L ulnar  acces d i g i t  Trisomy D syndrome: tower head, c i r c . of 11"; slanting e y e l i d s ; a t r o phic nose; B c l e f t l i p & palate; lowset, abn. ears; •flaccid neck; underdeveloped penis and scrotum; cryptorchidism; (?) D/D translocation  II'  B ulnar  pedicles  Trisomy D syndrome: i n f a n t i l e spasms; M R; upturned nose; long upper l i p ; centerline of soft palate prominent; m i l d l y dysplastic ears; small umb i l i c a l hernia; B cryptorchidism; simian crease R; D/D t r a n s l o c a t i o n D/D t r a n s l o c a t i o n  44  II  L ulnar  deformed acces f i n ger o f f 5th  45  II  L ulnar  rud. acces. d i g i t l a t e r a l to 5th with n a i l and c a r t i l a g e  L ulnar  acces predominantly soft tissue  5 46  III  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 p a r t l y fused to scrotum; cryptorchidism; calcaneal varus clubfoot R; M R ; trisomy of chrom.  B  fibular  47  II  L ulnar  acces 5th t i e d o f f  48  II  L ulnar  skin tag  17-18  159  B i r t h Ethnic Mat. Pat. Source , , _ , no . . or„ Birthdate Proband Sex place o r i g i n age age inform. Be  NInd  26  28  MRec DCJ  10 Sep 67  R  M  Bd  22  MRec  2 Mar 66  KDB  P  Ac  25  MRec  11 J u l 66  BAB  M  MRec RBL  16 Nov 66  B  M'  Af  NInd  35  39  Pedigree  D-r-O  D-r-O  43  45  6 66 * DO - r O  6 6 A6 i*  E  19  28  —  MRec  24 Feb 66  RM  M  Q-T-<)  47  MRec  24 Feb 64  MDT  F  Q - p O  48  Proband Position m,. number pedigree  49'  ~ ... „ ,. . , Description of supern. d i g i t s  L ulnar  II  s k i n tag  A d d i t i o n a l anomalies coarse s k i n  II-  D & C revealed t i s s u e of a f e t u s , development had ceased e a r l y i n g e s t a t i o n  II  hydrocephaly;  50  II'  L ulnar  s k i n tag  51  II  L ulnar  p e d i c l e o f f 5th at l e v e l of prox phal  52  II  L ulnar  p e d i c l e o f f 5th at l e v e l of prox phal  14  L ulnar  p e d i c l e o f f 5th at l e v e l of medial phal  II  L ulnar  pedicle  III  L ulnar  pedicle  B ulnar  acces d i g i t s normal length of 5th but perpendicular to 5th d i g i t s , d i d not bend  L ulnar  p e d i c l e without a n a i l & probably no bony t i s s u e  I  L ulnar  wartlike pedicle  11^  L ulnar  acces 5th connected by a long p e d i c l e , tied off  II  54  55  tongue-tie; prepuce retracted ptosis L  II  55  hematoma on head  1 II  2 56  II 2  57  hernia  5 58  II  CHD  • L ulnar  s k i n tag l a t e r a l o f f 5th' at l e v e l of prox phal, no bone or c a r t . B lopped ears  161 B i r t h Ethnic Mat. Pat. Source ,, , , _ , , „ . . or_ Birthdate Proband Sex place o r i g i n age age inform. • Gh  Wind  20  28  MRec DCJ  19 Apr 64  DRMK  MRec  18 Aug 67  L  M  Gc  20  MRec  22 Sep 66  S  M  la  Wind  17  20  MRec DCJ  14 J u l 65  BAR  M  L  Ind  37  46  MRec DCJ  22 J u l 65  BAC  P  MRec  2 0 J u n 66  CPC  M  Bd  Wind  21  22  MRec DCJ  30 Apr 67  RBA  M  Bd  Wind  24  (27)  MRec DCJ  21 Sep 65  WDJ  M  Cd  —  29  MRec  21 Sep 66  Ba  Wind  28  MRec DCJ  4 Nov 66  27  49  •o  6 4^6 6 6  25  24  . D"  M  Ba  Ba  Pedigree  H  RQL  Q-  •O  50  51  52  D4-O  53  D-T-O /  5 4  TL Q—,—HL]6  /  O-rO  P  55  56  57  58  M  D-r-O •  6  6 6  i  Proband P o s i t i o n xn,. number pedigree  59  II  60  II  1  _ ... „ ,. . , Descrxptxon or supern. dxgxts L ulnar  acces phal o f f 5th at l e v e l of medial phal, attached by skin  L ulnar  pedicle with c a r t i l . center o f f prox phal of 5*, no n a i l  II'  61  L ulnar  ll  U ulnar  62  II  L ulnar  pedicle with c a r t i l . tissue attached to medial phal of 5th  63  II  L ulnar  pedicle with c a r t i l . tissue  pedicle with v e s t i g . n a i l , no bony tissue  IIII-  anomalies  cancer  Hi-  64  Additional  pneumonia, age 6 weeks L.ulnar  pedicle with bone & a fingernail  operation f o r squint  abnormal heart valve  65  II  L ulnar  66  II'  B ulnar  ¥ D acces d i g i t , tongue-tie articulates laterally with head of 5th metac Smith-Lemli-Opitz syndr.: intrauterine growth r e tardation; postnatal f a i l u r e to thrive; microcephaly; 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; cutaneous p i t anterior to anus; synd toes 2-3; 8/ 10 whorls; Hirschsprungs Disease  163 B i r t h Ethnic Mat. Pat. Source , , _ , ,„ . . • of„ Birthdate Proband Sex place o r i g i n age age inform. •• • • Aa  —  33  —  MRec  23' May 65  AM  P  Be  Nlnd  37  40  MRec  20 Feb 65  DMS  P  Pedigree  D-r-O  59  60  O  DCJ  / Bb  Hind  36  36  MRec DCJ  2 May 66  SJK  61'  Q-  P  ffTrO  7>  6 ill i 4 1  E  • Kind  30  29  MRec DCJ  14 Nov 66  JLH  P  Aa  Nlnd  22  22  MRec DCJ  14 Jan 66  SC  M  Ob  Nlnd  27  32  MRec DCJ  21 May 66  KAH  P  D-r-O  o  C H j O  D  62  63  64  f 19  E  Hind  31  34  MRec  16 Oct 66  DSL  M  MRec JRM DCJ  24 Dec 65  SJR*  P  I  D-r-O  •  ^ o r i g i n a l l y described by Lowry et a l . , 1968.  65 66  Description of stipe rn-. d i g i t s B ulnar  f a i r l y ¥ D acces, no articulation  L  pedicle  ulnar  Additional anomalies  tongue-tie; feet  abnormal  B ulnar  pedicles, no bony tissue  B ulnar  acces at base of 5th  B ulnar  acces d i g i t L ; acces d i g i t R  B ulnar  B: a r i s i n g from prox phal; L better dev. with whorl on fingert i p ; R consists of a pedicle  B ulnar  pedicles  antimongoloid slant; heart murmur; floating, kidney; B hernia; synd.  B ulnar  pedicles  complete B c l e f t l i p ; c l e f t palate, absence of median maxillary process; hypogenitalism: penis exceedingly small with l i t t l e e r e c t i l e tissue, s c r o t a l sac extremely . small; cryptorchidism; agenesis, of p i t u i t a r y ; hypoplasia of adrenals; thymic tissue i n thyroid; no c l i n i c a l CHD  large fontanelle; microphthalmia; B ' c l e f t l i p & palate; small, (?) lowset ears; C H D : P D A & foramen ovale, hypertrophy R vent r i c l e , large septal defect; kidney abnormal.; cryptorchidism  rud.  Trisomy D syndrome: microcephaly; absence of f r o n t a l areas of brain; peculiar pigmentation on forehead & upper eyelids; anophthalmia; broad nose; hypop h e l i x L ear; c l e f t palate; C H D ; absence of R 12th r i b ; umbilical her. nia; clenching of hands; D/D translocation  165 B i r t h Ethnic Mat. Pat. Source , , „ , ,„ . . or„ Birthdate Proband Sex place o r i g i n age age inform. D  Nlnd  22  23 ' MRec DCJ  17 J u l 6"5  MAGK  M  Bh  Nlnd  31  44  MRec DCJ  2 J u l 67  BJG  M  Nlnd  22  27  MRec DCJ  11 Dec" 67  SPR  M  Bd  Nlnd  24  24 ' MRec JRM  16 Jun 66 • .  LDP  P'  31  MRec DCJ  17 Feb 65  WEN  M  MRec  14 Feb 65  MWH  M  Aa  Nlnd  28  22  67  Q-j—O  O r O  68  •  E  Ba  Pedigree  D-r-O  69  70  D-  -O  D-i-O  5T^  71  72  Proband P o s i t i o n number pedigree  73  1  II  II  74  III-  ir  Additional anomalies  B ulnar  pedicles at base of 5th, t i e d o f f  hypotonia, quadriplegia; cerebral hypoplasia; hydrocephalus; M R; flame naevus over forehead; depressed bridge to nose; somewhat small eyes; lowset ears; p a r t i a l c l e f t palate and uvula; enamel hypop. of teeth; hearing handicapped; e l e c t r o l y t e imbalance; CHD; polyc y s t i c kidneys'; developed anemia  L fibular  p a r t i a l l y synd acces 5th toe, with n a i l  large head, c i r c . 38 cm; hydrocephalus; patent fontanelles B; prominent forehead; deeply set eyes; epicanthic f o l d s B; depressed nasal bridge; lowset abnormal ears; Vshaped notch i n posterior edge of hard palate; large thymus; large polyc y s t i c kidneys B; small acces spleen; chromosomes: normal XX complement; l i v e d 2rz hours  B ulnar  pedicles  B ulnar  8  II  Description of supern. d i g i t s  B ulnar  75  II-  'B ulnar  pedicles  76  II  B ulnar  L: pedicle o f f prox phal. of 5th, no bone; R: t i n y nubbin of tissue o f f prox phal of 5th  s t i l l b o r n , died about 4i* 5th month of gestation  II  77  bowel obstruction due to hydrocoele of t e s t i s R  II  B ulnar  skin tag o f f 5th  i n d i r e c t inguinal hernia R  B i r t h Ethnic Mat. Pat. Source _.. no , . . or„ Birthdate Proband Sex place o r i g i n age age inform. Ba  Nlnd  19  30  MRec  12 Nov 66  DGA  P  Ba  Nlnd** 34.  33  MRec DCJ  20. Aug 66  WDPB  M  +  T, • Pedigree °  O—r~0  13  74  6 6>*h <£> 4 D-r-O  6 6666*664  Cc  —  21  E  Nlnd  35  33  MRec  20 Mar 67  RJP  M  MRec DCJ  26 Dec 64  GPT  M  D-r-O  ^  76  6 i 6• +  Cd  Nlnd  22  (22) MRec  25 J u l 64.' MAP  **one grandparent of French-Indian descent  .M  75  D-r-O  Proband P o s i t i o n in number pedigree  78  Description of supern. d i g i t s  Additional anomalies  IV  B ulnar  pedicles with, n a i l  L: synd. toes 2 - 3 the complete length; R: synd. toes. 1-2-3 complete length; died of pneumonia  IV  B ulnar  acces fingers f a i r l y ¥ D with n a i l s ; very broad thumb L; L: acces toe with duplic. metat fused to normal 1st metat; R: rud. nubbin l a t e r a l to main toe  R: synd. f i n g e r s 3-4—5 complete length with bony union d i s t a l l y of 3-4; L: synd fingers 3—4 the complete length; f e e t : synd. toes 1-2-3 B  B tibial  in*  radial  wide thumb with i n dented n a i l ; deformed 5th f i n g e r u n i l a t e r a l  III' III  8  II  synd. toes 2 - 3 B ulnar L tibial  pedicles; duplic. d i s t a l phal' with bone, no a r t i c .  TJ r a d i a l  f l a t wide thumb with indentation i n n a i l ; deformed 5th f i n g e r B, wide d i s t a l l y  ? ulnar  II*  L radial  ? ulnar  79  80  II*  B ulnar  B  f l a t wide thumb with heart attack s l i g h t indentation i n n a i l ; L: p a r t i a l synd fingers 4 - 5 with camptodactyly. of 5th; R: p a r t i a l synd 4-5, 5th i s wide d i s t a l l y pedicles  II  premature, approx 6 mo, gestation  II  premature, approx 7 mo. gestation  II*  high palate; l o r d o s i s  II'  inguinal hernia  II  B ulnar  pedicles  eczema  169 B i r t h Ethnic Mat. Pat. Source _,. , , , ,„ . . of_ Birthdate Proband Sex place o r i g i n age age inform. Ab  Nlnd  20  22  MRec  27 Aug 64  Pedigree O-r-O  CLN  •  Nlnd  27  36  MRec DCJ  11 Aug 64  JDP  •  •  78  i  D-r-O  M  •  79  •+D 6 6 • 6 +  Bd  Nlnd•  36  39  MRec DCJ  21 May 66  JtfP  M  80  Additional anomalies 81  II  B ulnar  pedicles  hemangioma on head  82  II  B ulnar  pedicles o f f 5th at l e v e l of PIP j o i n t , (?)medial aspect, suggestion of n a i l s  s y s t o l i c murmur  II-  stillborn  83  II  B ulnar  skin tags  hemangioma of scrotum  84  II  B ulnar  skin tags on l a t e r a l aspect of 5th  hypoglycemia  85  III  B ulnar  skin tags at base of 5th, l a t e r a l aspect  L tibial  p a r t i a l d u p l i c . of toe, synd. nearly to tip  B ulnar  acces d i g i t with bone and n a i l but no a r t i c u l a t i o n , tied off  R ulnar  small wartlike acces digit  III  L ulnar  acces d i g i t with bone and n a i l but no a r t i culation  III  B ulnar B fibular  acces d i g i t s f a i r l y ¥ D with bone and nail  5  III  7 86  «  III 2  III 3  B synd toes 2 — 3 about h a l f the length  ir  II II  L  radial  broad thumb  8  B synd toes 2 - 3 about a quarter of length L  radial  broad thumb  171  B i r t h Ethnic Mat* Pat. Source _. ,, , , _. . . „-.• . . • " or„ Birthdate Prohand Sex place o r i g i n age age' inform. L  Kind  31  Ba  NInd  35  31  MRec DCJ  1 Aug 64  MRec  13 J u l 65  C AH  F  SJP  P  Pedigree  82 D  L  NInd  Ba  21  27  21  MRec DCJ  23 Aug 67  MRec  4 Bet 65  RWM  -  j  O  -  H  D  M  03 h - T - n  /  D - r O  LL  81  Q—|—O  M  j  Q  84  i  Aa  NInd  30  31  MRec  12 Jan 67  JDW  /rs+  M  85  -o  L  NInd  39 .. 49  MRec DCJ  16 Aug 64  LAW  M  86  0  Proband P o s i t i o n „ j - •+ • in,. D e s c r i p t i o n of supern. d i g i t s number pedigree _ _ 87  A  B ulnar  rud. acces d i g i t a t tached to (?)medial aspect 5th f i n g e r 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 s k i n .  A d d i t i o n a l anomalies hematoma L upper arm  Down's syndrome  IV III  R radial  II  radial  webbed toes  88  II  B ulnar  L: large p e d i c l e ; R: w a r t - l i k e p e d i c l e ; both with bony t i s s u e  89  II  B ulnar  L: p e d i c l e w i t h bony and c a r t i l a g i n o u s t i s s u e ; R: s k i n tag  90  III  B ulnar  p e d i c l e s with bony d i s t a l phal and n a i l  1^  B ulnar  91  II  B ulnar  5th metac broad and bifid articulating with 5th and acces.  92  II  R fibular  ¥ D acces f o l d s over top of f o o t , p a r t i a l syndactyly with 5th  f e e t s l i g h t l y pronated  ears abnormal  epilepsy since age 5 or 6 93  II'  •B f i b u l a r  complete ¥ D acces 5th toes  II  R ulnar  wart-like pedicle on l a t e r a l aspect at base of 5th  hernia  pneumonia 94  L fibular  probably f a i r l y ¥ D  173 B i r t h Ethnic Mat. Pat. Source . ,, , , ^o . . or „ Birthdate Proband Sex place o r i g i n age age i n f o r m . _ _ _ _ _ _  Pedigree  T5  lb  NInd  25  30  MRec DCJ  18 Oct 66  TAT  M  -o  O  -o  87  •6 rj _ 6 6 • +  D  _7rr_ Ba  —  Gc  Ca  NInd  D-T-O  88  24  MRec  7 Peb 67  SLB  P  17  MRec  7 Nov 64  ILS  P  89  20  MRec DCJ  28 Jun 66  JIS  M  90  D- - o - T - a  i M  4  91  Ba  NInd  30  29  MRec DCJ  21 Nov 66  AMG  Ba  NInd  38  37  MRec DCJ  23 May 66  MGAS  o/ 6 66*6  92  Ca  NInd  26  33  MRec DCJ  25 Jun 66  DWC  M  93  M  D-  D-  -o  • &- a6  Ae  Ind  MRec  1 Sep 64  JPS  M  O  94  Proband P o s i t i o n number pedigree  Description of supern. d i g i t s  95  II  B fibular  L: skin tag R: acces & 5th a r t i culate with broad me tat,' both move actively  96  IF  R fibular  tied off  97  ir  R fibular  pedicle  98  II  L fibular  c a r t i l a g . mass to l a t e r a l side of main d i g i t , appeared as enlarged l i t t l e toe  B fibular  double toe n a i l s on 5th, acces l a t e r a l  4 99  III  Additional anomalies  narrow, high arched palate; very lowset ears; s y s t o l i c murmur along LSB; spina b i f i d a ; abdomi n a l musculature & subcutaneous tissue somewhat atrophic or hypop, r e c t a l prolapse  functional heart murmur  4 II  B fibular  double toe n a i l s on  5th 100  II  L fibular  broad 5th toe, indentation & division into two n a i l s heart defect; abnormality of lungs; colostomy u n t i l age 2; hernia  101  II  R fibular  broad 5th toe, redupl. of phals with some abnormality of me tat, l a t e r a l excised  102  II  B fibular  L: small acces phals L ear tag; tongue-tie medial, synd almost . complete length A-5> two n a i l s ; R: small acces phals l a t e r a l , synd 4-5-A to n a i l , 5th & acces share n a i l  175 B i r t h Ethnic Mat. Pat. Source , . , . . or„ Birthdate Proband Sex place o r i g i n age age inform.  Pedigree  0  Ba  —  20  —  MRec  8 Feb 66  FKF  M  Q-r-O  95  *6 6 • /  4  Ic  Nlnd  34  34  MRec DCJ  25 Sep 64  RZS  F  D-r-O  96  5To~i  D-r-O  97  (Ba)  Nlnd  24  28  MRec DCJ  6 Jun 67  JRD  M  Ba  Nlnd  25  26  MRec DCJ  7 Nov 66  DJE  M  98  Ba  Chin  24  26  MRec 29 J u l 64 DCJ •  ¥KL  M  99  6 6 6i-po Oa  Ind  25  32  MRec '*• DCJ  6 Feb 65  DGM  M  D  -O  • 6 • • 6m Be  Nlnd  32  32  MRec DCJ  19 May 66  MAP  F  D  •O  101  D6D4D Ac  Nlnd  19  22  MRec DCJ  12 Sep 67  ALF  M  D- -o  102  Proband P o s i t i o n m,. number pedigree  ^ ... „ ,. . , Description of supern. d i g i t s _ _  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  I  L fibular  enlarged 5th toe with two n a i l s  IV  L fibular  two toes a r i s i n g from 5th metat, each with two phalanges  III  L fibular  skin tag o f f 5th  106  II  L fibular  acces small, l a t e r a l prox & d i s t a l phals calcified,, well formed toe but did • not bend  107  II  B fibular  L: very broad 5th metat with two a r t i cular surfaces on i t s head; R: f i v e metatarsals  1  105  8  Additional  anomalies  Pierre Robin anomaly: glossoptosis; high soft palate; hard palate; midl i n e longitudinal ridge represents an i n c i p i e n t c l e f t palate with vomer v i s i b l e ; micrognathia  II  drowned  II"  died when i l l with high fever  II  l i v e d one  II'  l i v e d s i x days  108  II  L fibular  f i v e metats, acces . a r t i c u l a t e d with MP j o i n t , n a i l present  109  II  L fibular  acces toe inserted between the 4th & 5th, bony spur seemed to a r t i c u l a t e with 5th metatarsal  day  177 B i r t h Ethnic Mat. Pat. Source -n , , . . or„ Birthdate Proband Sex place o r i g i n age age inform.  Pedigree  0  Ba  Bd  Gb  —  Ind  . 31  19  o  MRec • 3 Mar 66  KAK  P  —  MRec PHN  16 Mar 65  RMC  P  104  22  MRec DCJ  17 Peb 65  PDGM  M  105  17  103  T Ba  NInd  29  34  MRec DCJ  29 Apr 66  GMC  M  y /  106  A  • — r O  cTiTl) Nc  NInd . 37  41  MRec DCJ  22 Jun 67  NMV  M  107  • — r - O  •  D  +  D 6 6 6 +  Be  Orie  29  —  MRec  3 Nov 67  DAY  M  E  —  33  --  MRec  19 Jan 64  CMY  M  +  Chr^O /  _6  108  109  Proband Position in,. number -pedigree 110  V  .15  VI  ^ ... „ . . , Description of supern. d i g i t s _ 1  B fibular (2 acces L)  B ulnar  B fibular  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 B: rud. acces metac. inserted between 4th & 5th metac, prox phals of acces & 5th fused by c a r t i l a g . epiphysis, synd A-5 to middle phalanx; B:common 5th metat, 5th & acces prox phals side by side, no oss i f i c a t i o n centers f o r acces middle or d i s t a l phals; L: synd 5 - A  B ulnar B fibular B ulnar B fibular  V  B ulnar U fibular  V  V  10  •14  B ulnar B fibular B tibial  B f i b : acces i n serted between 4 * &  R ulnar B fibular  .uln: wide 5th finger & nail; f i b : lateral  B ulnar (2 acces B)  B fibular*  Additional anomalies  5th  L: metacs 3 - 4 fused at base, rud acces metac medial to normal 5th, p a r t i a l synd A - 5 j addtnl acces l a t e r a l to 5th: skin tag with c a r t i l a g e ; R: rud 6th & 7th metacs, synd 5 - 6 complete length, 7th has two phals; B f i b : s i x metats  179  B i r t h Ethnic Mat. Pat. Source ^. ,, , , -n , , . . or„ Birthdate Proband Sex place o r i g i n age age inform. 0  Bb  -Nlnd  30  MRec DCJ  36  i 6  •  i  8 Oct 65  i  JhrO  RHA  M  i-rO  Pedigree  Proband P o s i t i o n number pedigree 110  Description of supern. d i g i t s  rr  B ulnar B fibular  '¥ D d i g i t s on the hands and feet  IV  B ulnar B fibular  u l n : nubbins f i b : ¥ D digits  IV^  B ulnar  u l n : nubbins, synd 4 - 5 the entire length f i b : ¥ D digits  B fibular  Additional anomalies  Q IV  B ulnar B fibular  u l n : nubbin L; R has acces medial to 5 t h ; f i b : acces numeric a l l y the 4 t h toe  q IT 2III-  B ulnar ? fibular.  nubbins on the hands and feet  B ulnar B fibular  u l n : nubbins, synd R f i b : ¥ D digits, synd  B ulnar B fibular  ¥ D d i g i t s on the hands and feet  U ulnar ? fibular  nubbin  4  III II'  polyd 111  II  L fibular  acces toe inserted between the 4 t h & 5 t h , acces metat projecting from 4 t h with somewhat hypop prox & d i s t a l phals, synd A - 5 to prox phal  112  II'  B fibular  B: acces medial to 5 t h , 5 t h & acces both a r t i c u l a t e with 5 t h metat; R: no proper n a i l ; L: n a i l present  113  II  R fibular  acces toe medial to 5 t h , metat present  114  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 c a r t i l a g e , ¥ D toe with 3 phals  5  cataract R eye  asthma; eczema  181 B i r t h Ethnic Mat. Pat. Source T, , , „ . . or. Birthdate Proband Sex place o r i g i n age age inform.  Pedigree  n  Be  18  —  MRec  15 Oct 67  LDH  P  ' Q—i—Q  111  31  —  MRec  11 Dec 65 • JAD  M  r-X  112  Ba  NInd  26  27  MRec DCJ  11 Dec 67  LGM  Ic  wind  32  36  MRec DCJ  27 Jun 64  DLM  -o  113 114  /  6  D-i-O  6'A)  1  Description of supern. d i g i t s R fibular  p a r t i a l synd of 4th and acces  B ulnar B fibular  acces d i g i t s at base of 5th  Additional anomalies  p i l o n i d a l sinus; enlarged liver CHD;  B ulnar  sternal anomaly  finger-shaped and attached at 5th metac, no a r t i c u l a tion (?); toe-shaped, no a r t i c u l a t i o n (?),synd. toes 2-3 and 5-A L, 2-3 R  Smith-Lemli-Opitz syndr.: elongated head, suggestive of microcephaly; ptosis; broad maxillary alveolus; high arched palate, no c l e f t ; micrognathia; large pinnae, somewhat low and slope backwards; short neck; pigeon chested; anomal o u s ext. g e n i t a l i a ; complete ventral hypospadias with b i f i d scrotum; cryptorchidism; hips do not abduct f u l l y ; feet tend to be i n c a l caneovalgus position; XY chromosome complement b i r t h mark on l a b i a major  R fibular  small bony spike on under side of 5th rud. acces. toe a t tached by twisted pedicle, with n a i l  B ulnar R fibular  pedicles with n a i l ; pedicle, no n a i l  IJ f i b u l a r  acces d i g i t s  L ulnar B fibular  pedicles  B. ulnar  R: ¥ D acces with phals & n a i l , t i e d o f f ; L: better developed, excised  L fibular  R ulnar  r  B supern. nipples below normal ones  cerebral palsy; R hemiplegia; speech problem  183 B i r t h Ethnic Mat. Pat. Source , , _, , , _ . . .. of _ Birthdate Proband Sex place o r i g i n age age inform. . E  P  Ind  Nlnd  19  —  MRec  19 Mar 65  AGS  42  42  MRec DCJ  6 Mar 64  AD  Pedigree  P  115  P+  Q-  -O  6 6 6 6 6 6 6 •*  116  +  Af  Nlnd  18  22  MRec RBL  3 Nov 67  TMK  M  Id  Nlnd  25  25  MRec DCJ  1 Sep 65  WLS  P  Q—rO  D-  -O  117  118  6 6* • Na  Ba  Ind  Nlnd  20  21  MRec DCJ  31 May 66  KAS  P  119  17  19  MRec RBL DCJ  14 May 67  KBJ  M  120  •6-r-a 6 6 i •  d 6 •  Description of supern. d i g i t s B ulnar  B fibular  B ulnar  acces fingers with three phalanges, no acces metacarpal, no a r t i c u l a t i o n ; L: single phal precursor; R: acces with two rud. phals  Additional anomalies two b i r t h marks  acces o f f prox phal  B ulnar B ulnar  B fibular  L: pedicle; R: acces with osseous or cartilaginous connection; L: head of 5th metat broad, acces medial to 5th, acces & 5th a r t i c u l a t e ; R: hypop acces toe, no a r t i c .  R ulnar  pedicle  L ulnar  pedicle  B ulnar (2 acces R)  R fibular B ulnar B fibular  antimongoloid slant to eyes 7  L: acces d i g i t R: acces d i g i t l a t . to 5th with 2 or 3 phals, no metac; plus 2nd acces d i g i t inserted between 5 & 4 with 3 phals and rud. metacarpal; acces d i g i t  muscle tone poor; hypertelorism; micrognathia; high arched palate; CHD: VSD, R v e n t r i c u l a r hypertension, markedly dextroposed a o r t i c root, complete pulmonary artery a t r e s i a with a hypop. main pulmonary artery, PDA; synd. toes 2-3 B  finger-shaped d i g i t s with bone, no a r t i c , B: acces toe with 1 phal, a r t i c u l a t e s to l a t e r a l aspect head of 5th metatarsal  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  B ulnar B fibular  finger-shaped d i g i t s without bone; acces toes with bones  chronic constipation problems; synd. toes 2 - 3 : R 2 / 3 the length, L 1/3 the length  185 B i r t h Ethnic Mat. Pat. Source ~. ,, , , - , , „ or„_ Birthdate Proband Sex place o r i g i n age age inform. Ob  Nlnd  23  —  MRec DCJ  U  J u l 64  MJS  '  ^. Pedigree  P  121  2>*  1  6| • ^66+^6*6+6  E  Nlnd  34  30'  MRec DCJ  29 Oct 66  SB  Ca  Nlnd  22  24  MRec DCJ  23 Jan 64  DLN  P'  o-  122  O-r-O  123  6 6 * * +  Ad  Nlnd  26  27  MRec DCJ  21 Sep 67  CCC  M  O  o  124  •o  6~i~b  Proband P o s i t i o n m . number pedigree n  125  IV  _ ... „ ,. ., Description or supern. d i g i t s _ •B ulnar  B fibular  IV  nonfunctional fingershaped .digits barely attached; whorls on f i n g e r t i p s of acces; acces appeared ¥ D, inserted between 4th and 5th  ? polyd  Giant c e l l h e p a t i t i s : c i r r h o s i s of l i v e r and l i v e r f a i l u r e ; cong. a t r e s i a of the common b i l e duct  IV  126  B fibular  8  II'  acces 5th toes  B ulnar B fibular  B ulnar B fibular  acces d i g i t s ¥ D with three phals, no s i x t h metac or metat, minimal synd of 5th and 6th d i g i t s v i r u s pneumonia  IV  B ulnar B fibular  B acces d i g i t s a r t i culated with 6th metac or metat, L 6th f i n g e r less ¥ D  III  B ulnar B fibular  pedicles, t i e d o f f ; B: ¥ D acces, a r t i c . with 6th metatarsal  nr  L fibular  a r t i c u l a t e d (?)  II I  Giant c e l l h e p a t i t i s : ASD; lowset ears; malformed gums CHD: cong. spondylol i s t h i o s e s ; primary lower i n c i s o r s never erupted; perforation of R eardrum  II 127  Giant c e l l h e p a t i t i s : low l y i n g ASD with m i t r a l and t r i c u s p i d i n s u f f i ciency due to hypop. of septal cusps; congenital atresia of b i l e ducts (common b i l e duct); p i l o n i d a l dimple arthrogryposis multiplex congenita; CDH; abn. of t e s t i c l e s and scrotum  IV  III  Additional anomalies  fibular polyd  187 B i r t h Ethnic Mat. Pat. Source . ,,, , „ , , place o r i g i n age age of„ inform. Birthdate Proband Sex  Pedigree  T)  Ba  Wind  24  28  MRec RBL  16 Aug 67  BTAS  M  Q-  -o  125  6+6 ti o ti 6 6=|6lj] 6  Ch  NInd  26  32  MRec DCJ  13 May 66  GFT  M  *+*  O  Q"  i  NInd  23  23  MRec DCJ  23 Mar 65  MGK  M  126 d  I  -o  oi l l  O  cv7>  127  Description df supern. d i g i t s R ulnar  B fibular  Additional  anomalies  small finger-shaped d i g i t with 3 phals, a r t i c u l a t e s with head of 5th metac.5. ¥ D acces l a t e r a l , a r t i c u l a t e s with b i f i d 5th metat L, . broad head of 5th metat R  B ulnar B fibular  ¥ D acces d i g i t with 2 phals, rud. 6th metac ..or metat fused to 5th, acces has a small j o i n t  hyperactive; epicanthic f o l d s ; VSD; CDH L  B ulnar  acces perpendicular to 5th, a r t i c u l a t e s with 5th metac, L i s f a i r l y I D , R i s ¥D; 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  acces almost at . r i g h t angle to 5th, a r t i c u l a t e s with 6th metac L, with b i f i d 5th metacarpal R; ¥ D acces: L a r t i culates with 5th metat, R 6th metat fused to base of 5th; R: medial deviation of d i s t a l phal of great toe  Laurence-Moon-Biedl syndr d i f f i c u l t y with eyesight  pedicle L: ¥ D acces, 5th & 6th metat fused at base; R: acces less ¥ D, bone fragment l a t e r a l aspect head of 5th metatarsal  Laurence-Moon-Biedl syndr mild M R; triencephaly;" r e t i n i t i s pigmentosa; hirsute; mild gynecomast i a ; obesity; diabetis insipidus; hypogonadism, cryptorchidism L; broad spatulate fingers  B fibular  B ulnar  B fibular  L ulnar B fibular  misc. at approx 23 weeks L hand  189 B i r t h Ethnic Mat. Pat. Source . . of^ Birthdate Proband Sex place o r i g i n age age inform. of _ m f orm Ba — 31 — MRec 10 Mar 67 JMT M  Pedigree  r c e  L  Ind  (21) —  MRec  22 Apr 67  MM  •o  o  M  128  129  6-i~6 K  Ind  25  —  MRec  2 Apr 67  RL  M  o  O  PM  6  Gc  NInd  40  44  MRec EC J  27 Apr 65  AB  M  —  26  —  MRec  23 Jul; 64  HMH  M  130  6%Tb  -o  ' CD-  131  cY m  •  Be  -•  O  O  132  Proband P o s i t i o n in.. number pedigree 133  II  1 2  _ ... „ ,. . , Description of supern. d i g i t s _ _  A d d i t i o n a l anomalies  R hand  cerebellum somewhat small; receding c h i n ; CHD: i n t e r v e n t r i c u l a r s e p t a l 'defect, unusual globular shape; abn. m u l t i l o b u l a t e d l i v e r ; cryptorchidism; protuberant heels and rockerbottom appearance of feet  extra d i g i t  birthmark on neck and  • II134  II  135  II  2  .33 hands  pedicles, tied off  R foot  acces phal attached to metac; t i n y n a i l  tongue-tie  8 136  II '  B feet  II  ? polyd  137  II  138  II  7  5  .  abn. buttock crease . B feet  B feet 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  arm  191 B i r t h Ethnic Mat. Pat. Source _. , , „ , ,„ . . or„ Birthdate Proband Sex place o r i g i n age age inform. Be  NInd  45  53  MRec DCJ  7 Nov 67  L  M  Pedigree 133  +  _ 6 _ '6 _ 6 6 _ _ 4  Bb  24  MRec  18 Jun 66  LDH  P  22  MRec  14 Oct 64  WP  M  MRec PHN  25 Jan 64  TCS  M  Nb  Ba  Bb  37  -o  D"  /-N  Ur~r—O—rO  6  i7>  6 6 6 6 66 6* MRec  28 Jun 65  MRec  1 J u l 66  ECT  M  »—•—I  J  134  135  136  137  ^ — [ — -  6 P 6~_  ' N .' M'  +  138  1 92 Appendix B  Dermatoglyphics  In many cases dermal ridges i n the immediate area of•attachment  of an  accessory d i g i t are s u f f i c i e n t l y c h a r a c t e r i s t i c to determine Polydactyly had been present at b i r t h even though the d i g i t s themselves have been removed (Cummins, 1926;  Cummins & Midlo, 1943;  Temtamy, 1966b).  An accessory d i g i t a l  t r i r a d i u s can nearly always be distinguished i n cases of ulnar Polydactyly. This t r i r a d i u s i s closely associated with the s i t e of attachment of the supernumerary finger; and from i t s placement, the breadth of the concentric dermal ridges spanning the s i t e of attachment, and the relationship of this pattern to the major l i n e s of the hand inferences can be made regarding the extent of duplication of the accessory. Plate 1 shows the t y p i c a l dermal pattern associated with a rudimentary pedicle whereas patterns given i n Plate 2 r e f l e c t the presence of a well-formed supernumerary f i f t h finger.  Well-formed  and pedicle-type accessory f i b u l a r  d i g i t s (Plate 3) have associated dermal patterns s i m i l a r to t h e i r postaxial counterparts on the hands.  In addition duplication may be polysyndactylous,  i n which case an accessory t r i r a d i u s w i l l probably not be present. Preaxial Polydactyly may also be polysyndactylous, well-formed or of-a pedicle nature. surgery.  Plate 4 presents the p r i n t of a polysyndactylous thumb p r i o r to  The pattern on the t i p of the thumb extends across both f i n g e r t i p s ;  the d i s t a l b i f u r c a t i o n i s aligned with the common t r i r a d i u s . pared to the dermal pattern associated with nonsyndactylous  This can be comduplication of the  thumb, the accessory thumb a r i s i n g o f f the proximal phalanx of the p r i n c i p a l first digit. The l e f t hand and right' foot of a c h i l d with polysyndactyly are i l l u s t r a ted i n Plate 5.  P r i o r to surgery t i b i a l Polydactyly was present, however derma-  toglyphic features associated with the s i t e of attachment or b i f u r c a t i o n have been o b l i t e r a t e d .  Clearly seen i n the foot p r i n t i s syndactyly of toes one  through three.  An accessory t r i r a d i u s r e s u l t i n g from ulnar Polydactyly i s  apparent i n the hand p r i n t 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 a f t e r postminimus t i e d o f f (proband number 76)  Right above:  t r i r a d i u s of accessory d i g i t o f f proximal phalanx (proband number 119)  Left:  t r i r a d i u s of accessory d i g i t o f f medial phalanx (proband number 55)  Plate 2.  Dermatoglyphics of Ulnar Polydactyly Well-formed, a r t i c u l a t i n g d i g i t s  • .fe-  r  Above:  t r i r a d i u s of accessory d i g i t d i s t a l to t r i r a d i u s of 5th f i n g e r (proband number 1 3 1 )  Left:  t r i r a d i u s of accessory d i g i t proximal to t r i r a d i u s of 5th f i n g e r (proband number 131)  196 P l a t e 3.  Dermatoglyphics of F i b u l a r P o l y d a c t y l y  mm  . •."•..At-.i . V - ••••  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 l a t e r a l - m o s t toe proximal to t r i r a d i u s of the numerically 5th toe (proband number 127)  1 *  SB  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:  d e t a i l of thumb p r i n t of hand r i g h t ; the pattern extends across both f i n g e r t i p s with the t r i r a d i u s and b i f u r c a t i o n aligned (proband number 3)  Right above:  t r i r a d i u s of accessory d i g i t o f f proximal phalanx (proband number 1)  Right:  duplicated d i s t a l phalanx, both d i s t a l phalanges present (proband number 3)  Plate 5.  Dermatoglyphics  of Polysyndactyly  Hand: t r i r a d i u s of supernumerary d i g i t at base of 5th f i n g e r , 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 f o r 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 D a l l a i r e , 1962  6  German et a l . , 1962  8  Gottlieb et a l . , 1962  9 10 1  "  "  Koenig et a l . , 1962  •]  II  II  12  Rosenfield at a l . , 1962  13  Smith et a l . , 1962  14  15  ii  11  it  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  6 fingers ? B hands  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 H i l t o n , 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  P f e i f f e r , 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 L u z z a t t i ,  55  Windmiller et a l . , 1965  56  Taylor, 1968  57  1965  6 d i g i t s B hands  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 L hand  202 Part A.  (continued) 81  Taylor, 1968  82  Benady and Harris, 1969  83  "  "  84  "  "  85  "  "  86  "  "  B ulnar acces. d i g i t s  87  Chesler et a l . , 1970  88  Medical Genetics, U.B.C., No. 63-4  89  No. 65-6 .  90  No. 65-96  91  No. 66-74  92  No. 67-63 •  93  No. 67-123  94  No. 67-128  95  No. 67-170  96  No. 69-8  97  No. 69-23  98  No. 69-239  99  No. 70-79  100  No. 70-147  203  Part B.  References f o r Cases with Trisomy D.^ Syndrome  ^  Type of duplication  o  polyd.  ulnar • f i b u l a r  1  Patau et a l . , 1960  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  "  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  M i l l e r et a l . , 1963  B  R  13  Sergovich, 1963  14  Smith et a l . , 1963  15  "  "  16  "  "  +  L + L +  17  Warburg & Mikkelsen, 1963  18  Blanck et a l . , 1964  19  Lafourcade et a l . , 1964-  +  20  Marin-Padilla, 1964  +  21 22  "  •  it  24  "  "  Powars et a l . , 1964  R B  P f e i f f e r , 1964 II  25  •'  "  23  tibial  B  B  B  B  +  B B  B  +  unk.  204 Part B.  26  (continued)  Taylor & Polani, 1964  27  II  28  " "  ulnar  fibular  B  B  B  B  U  +  it  29  Eewis & Paint, 1965  30  Mehes & Bata, 1965  31  Mottet & Jensen, 1965  ^2  II  '•  ^3  II  it  34  No polyd.  +  +  Snodgrass et a l . , 1966  35  " "  36  " "  B  •yj  it  B  38  " "  39  ti  it  B  40  " "  B  +  M  41  Wilson & Melnyk, 1967  42  Butomo & Shushval, 1968  43  Taylor, 1968  +  +  44  " »  45  ti  46  " "  B  47  II  R  48  " "  49  it  tt  +  50  " "  +  51  " "  52  B  'i  I'  +  tibial  unk.  205 Part B.  53  (continued)  Taylor, 1968  Wo polyd.  ulnar,  fibular  B(7th)  B  55  B  B  56  L  57  B  58  B  59  L  60  B  61  B  62  B  63  B  64  R  65  B  66  +  67  +  68  +  69  Toews & Jones, 1968  +  70  Wilson, 1968  +  11  11  72  "  •'  unk.  +  54  7-]  tibial  B  L(7th)  73' James et a l . , 1969  +  74  +  "  'I 11  +  76  " "  +  77  11  it  +  78  " "  +  75  79  11  206  P a r t B.  (continued)  Wo polyd.  80  James e t a l . ,  1969  81  Bowen e t a l . ,  1970  82  Taylor et a l . ,  83  "  "  84  "  "  85  ulnar  fibular  :  tibial  unk.  + L  1970  L  + + +  Thorburn,  1970  +  86  "  "  +  87  II  ii  +  88  "  "  +  89  "  "  +  go  'I  'i  +  91  Yu e t a l . ,  1970  B  92  "  "  93  i.  II  L  B  94  "  "  L  B  95  B  M e d i c a l G e n e t i c s , U. B. Wo. 62-105  C, 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 f o r Cases with Polydactyly/imperforate Anus/Vertebral Anomalies Syndrome and Cases with Similar Anomalies Anomalies  Imperforate anus  digital  vert'eb.  r i b other  1  Puhrmann, 1968  +  +  2  Say and G-erald, 1968  +  +  +  3  ii it it  +  +  +  +  +  4  +  +  +  +  +  5  +  +  +  +  +  +  +  +  +  +  +  +  +  6  +  7  +  8  +  9  +  +  +  10  +  +  +  +  +  11  +  +  13  +  +  14  +  +  15  +  +  16  +  +  17  +  +  18  +  +  12  +  Tunte, 1968  +  + +  +  +  +  +  +  +  +  +  +  +  +  +  22  +  +  23  +  +  24  +  +  19  M i l l a r d , 1969  20  Kaufman et a l . , 1970  21  Townes and Brocks, 1970  25  +  208 „ Imperforate anus  digital  +  +  27  +  +  0  +  28  +  +  +  +  29  +  +  +  +  +  +  +  +  +  +  Part C.  26  (continued)  Say et a l . ,  1971  30 +  31 32  Anomalies verteb.  rib  other  +  +  33  +  +  +  +  34  +  +  0  +  35  Stieve, 191'  +  +  36  Keel,  +  +  37  +  +  +  38  +  +  +  39  1958  Stevenson et a l . ,  +  1966  40  +  +  41  +•  +  42  +  43  +  +  +  44  +  +  +  45  + +  +  47  Tan,  +  +  48  Reid and Woolf,  +  +  49  B.C. study, proband no.  +  +  124  +  +  Temtamy, 1 966b  1970  + +  46  1969  +  + +  

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