Phenotypic Variability from Benign Infantile Epilepsy to Ohtahara Syndrome Associated with a Novel Mutation in SCN2A

摘要

Mutations in SCN2A have been associated with benign familial neonatal-infantile seizures (BFNIS) as well as infantile-onset epileptic encephalopathy, such as Ohtahara syndrome (OS). We describe a family with 3 affected individuals carrying the novel SCN2A missense variant c.1147C>G, p.Q383E affecting a residue proximal to the highly conserved selectivity filter in the P-loop of the voltage-gated sodium channel (Na_v1.2). All 3 individuals presented with seizures in early infancy. However, there were striking differences in the spectrum of clinical presentations, ranging from BFNIS to OS. A change of ion selectivity of Na_v1.2 is considered to be the potential pathomechanism underlying this Na_v1.2 channel dysfunction. The observation of benign and severe pheno-types due to an identical mutation within one family contradicts the hypothesis of different modes of inheritance as a mandatory feature discriminating BFNIS from SCN2A encephalopathy.