Emma L Leach1, Clara D M van Karnebeek2, Katelin N Townsend3, Maja Tarailo-Graovac4, Juliette Hukin5, William T Gibson6. 1. Department of Medical Genetics, University of British Columbia, Vancouver, Canada. 2. 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. 3. Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Child and Family Research Institute, British Columbia Children's Hospital, Vancouver, Canada. 4. Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada. 5. Division of Neurology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver, Canada. 6. 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.
Abstract
INTRODUCTION: 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. CLINICAL PRESENTATION: 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. CONCLUSION: 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.
INTRODUCTION: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. CLINICAL PRESENTATION: 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. CONCLUSION: 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.
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