Epileptic Disorders - Editor's Choice Archive
The following are past Editor's Choice articles. Free access may not be available.
Confirming an expanded spectrum of SCN2A mutations: a case series
Dena Matalon, Ethan Goldberg, Livija Medne, Eric D. Marsh
Comments by Associate Editor Aristea S. Galanopoulou MD PhD
Mutations in voltage-sensitive sodium channels (SCN) have been increasingly identified in human epilepsy syndromes. These syndromes include both “benign” forms (e.g., benign familial neonatal-infantile epilepsy) and more severe types (e.g., Dravet syndrome, infantile epileptic encephalopathies). Matalon and colleagues here describe the clinical features of 3 girls with 3 different de novo SCN2A mutations that presented with early onset epilepsies, poor developmental outcomes and axial hypotonia. Thinning of the corpus callosum was eventually identified in two of the patients. Two of the girls manifested infantile spasms whereas the third had neonatal tonic seizures. In one of the patients with infantile spasms choreiform movements were also observed.
Of interest, a subsequent independent study by Hackenberg et al (Neuropediatrics, 2014) describes an identical mutation (c.4025T>C) of the SCN2A gene in a different girl who also presented with infantile spasms, choreiform movements, hypersomnia and progressive brain atrophy. These observations lend support to the pathogenicity of this specific mutation but also to its functional impact on both cortical and subcortical structures. Matalon et al nicely review the literature on genotype-phenotype correlations of the known human SCN2A mutations, discussing the inherent heterogeneity but also increasing evidence for a possible involvement of these mutations as modifiers of human epilepsies. Further studies are certainly needed to confirm the functional consequences of these mutations in the developing brain. The need for creation of comprehensive public access genotype-phenotype databases and animal models of the known and emerging epilepsy-related mutations is however becoming increasingly evident, so as to best study their clinical and pathogenic relevance.