Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy: A Molecular Neuropharmacological Approach.

ABSTRACT: Mutations in SCN8A are associated with epilepsy and intellectual disability. SCN8A encodes for sodium channel Nav1.6, which is located in the brain. Gain-of-function missense mutations in SCN8A are thought to lead to increased firing of excitatory neurons containing Nav1.6, and therefore to lead to increased seizure susceptibility. We hypothesized that sodium channel blockers could have a beneficial effect in patients with SCN8A-related epilepsy by blocking the overactive Nav1.6 and thereby counteracting the effect of the mutation. Herein, we describe 4 patients with a missense SCN8A mutation and epilepsy who all show a remarkably good response on high doses of phenytoin and loss of seizure control when phenytoin medication was reduced, while side effects were relatively mild. In 2 patient

SUBMITTER: Boerma RS 

PROVIDER: S-EPMC4720675 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature