title: Episodic ataxia associated with a de novo SCN2A mutation.
abstract: BACKGROUND
  Episodic ataxia (EA) 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 EA.
  
  
  METHODS
  This boy presented with clinical features of episodic ataxia, and also showed cerebellar atrophy, hypotonia, autism and global developmental delay at age 4 years. Acetazolamide prevented further episodes of ataxia, dystonia and encephalopathy. 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.
  
  
  CONCLUSIONS
  Considered alongside previous reports of episodic ataxia in SCN2A mutation-positive patients, our case further illustrates the genetic heterogeneity of episodic ataxia. In addition, this case suggests that acetazolamide may be an effective treatment for some aspects of the phenotype in a broader range of channelopathy-related conditions.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Leach
authors.affiliation: Division of Biochemical Diseases, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, Canada; Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Clara D M
authors.initials: CD
authors.lastname: van Karnebeek
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Katelin N
authors.initials: KN
authors.lastname: Townsend
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo-Graovac
authors.affiliation: Division of Neurology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, Canada.
authors.forename: Juliette
authors.initials: J
authors.lastname: Hukin
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, Canada. Electronic address: wtgibson@cfri.ca.
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human; D000086:Acetazolamide
keywords: Acetazolamide; Cerebellar atrophy; Channelopathy; Episodic ataxia; SCN2A; Treatment