SCN8A gain-of-function mutation is associated with a relatively mild phenotype of epilepsy

Abstract

Abstract SCN8A-associated epilepsy with encephalopathy has been identified in hundreds of individuals. The vast majority of cases are scattered de novo variants typically with an autosomal dominant expression often resulting in severe phenotypic expression. Familial inheritance has also been reported with diverse clinical features. The present study aimed determine the possible SCN8A pathogenic biophysical alterations associated with epilepsy. Using whole exome sequencing, we analyzed five members of a Chinese family and identified a heterozygous missense mutation of SCN8A (c.3926G > A, p.Arg1309Gln). All five affected members developed seizures at different times after birth with a mild clinical phenotype and no intellectual and behavioral development disorders. Low-dose sodium blockers mono-therapy was and effective seizure treatment. The study results suggests that the SCN8A mutation is associated with minor gain-of-function (GoF) effects resulting in the development of mild seizures, however, seizures are well controlled by sodium channel blockers. Therefore, our data broadens the spectrum of SCN8A mutations and the phenotypic-spectrum description of SCN8A mutations in epilepsy patients. In addition, these results suggests that sodium channel blockers may be the most effective treatment option for patients with GoF SCN8A mutations.