Episodic ataxia associated with a de novo SCN2A mutation

•Exome sequencing broadens genotype-phenotype correlations in known paediatric neurological conditions.•A novel, dominant SCN2A genetic variant associated with episodic ataxia phenotype.•Acetazolamide may be an effective treatment for a non-CACNA1A channelopathy.

IntroductionEpisodic 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 presentationThis 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.ConclusionConsidered 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.