Acetazolamide-responsive episodic ataxia associated with a de novo SCN2A mutation

UBC Faculty Research and Publications

Acetazolamide-responsive episodic ataxia associated with a de novo SCN2A mutation Leach, Emma L.; van Karnebeek, Clara D. M.; Townsend, Katelin N.; Tarailo-Graovac, Maja; Hukin, Juliette; Gibson, William T.

Abstract

Introduction: Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia interspersed by asymptomatic periods. Dominant mutations or copy number variants in CACNA1A are a well-known cause of EA2. Clinical presentation: This boy presented clinical features of EA2, and also showed cerebellar atrophy, hypotonia, autism and global developmental delay at age 4 years. Acetazolamide prevented further episodes of ataxia. Extensive biochemical and genetic tests were unrevealing; whole exome sequencing found a previously unreported variant in SCN2A, proven to be de novo and predicted to be protein-damaging. Conclusion: Considered alongside a previous report of ataxia in an SCN2A mutation-positive patient, our case further illustrates the genetic heterogeneity of EA2 and suggests that acetazolamide may be an effective treatment in a broader range of channelopathy-related conditions.

Item Metadata

Title	Acetazolamide-responsive episodic ataxia associated with a de novo SCN2A mutation
Creator	Leach, Emma L.; van Karnebeek, Clara D. M.; Townsend, Katelin N.; Tarailo-Graovac, Maja; Hukin, Juliette; Gibson, William T.
Date Issued	2016
Description	Introduction: Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia interspersed by asymptomatic periods. Dominant mutations or copy number variants in CACNA1A are a well-known cause of EA2. Clinical presentation: This boy presented clinical features of EA2, and also showed cerebellar atrophy, hypotonia, autism and global developmental delay at age 4 years. Acetazolamide prevented further episodes of ataxia. Extensive biochemical and genetic tests were unrevealing; whole exome sequencing found a previously unreported variant in SCN2A, proven to be de novo and predicted to be protein-damaging. Conclusion: Considered alongside a previous report of ataxia in an SCN2A mutation-positive patient, our case further illustrates the genetic heterogeneity of EA2 and suggests that acetazolamide may be an effective treatment in a broader range of channelopathy-related conditions.
Subject	Episodic Ataxia Type 2; SCN2A; Acetazolamide; Cerebellar atrophy; treatment; channelopathy
Genre	Article; Postprint
Type	Text
Language	eng
Date Available	2017-06-14
Provider	Vancouver : University of British Columbia Library
Rights	Attribution-NonCommercial-NoDerivatives 4.0 International
DOI	10.14288/1.0305069
URI	http://hdl.handle.net/2429/58322
Affiliation	Medicine, Faculty of; Non UBC; Medical Genetics, Department of
Citation	Leach EL, van Karnebeek, Clara D M, Townsend KN, Tarailo-Graovac M, Hukin J, Gibson WT. Episodic ataxia associated with a de novo SCN2A mutation. European Journal of Paediatric Neurology.
Publisher DOI	10.1016/j.ejpn.2016.05.020
Peer Review Status	Reviewed
Scholarly Level	Faculty; Researcher
Copyright Holder	Elsevier (European Journal of Paediatric Neurology)
Rights URI	http://creativecommons.org/licenses/by-nc-nd/4.0/
Aggregated Source Repository	DSpace

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