Abstracts

Rationale: SCN8A encodes one of the main voltage-gated sodium channel subunits (Nav1.6) in the brain. Mutations in SCN8A-gene been recently described in patients with mental retardation, epilepsy and neurological deficits (Larsen et al, 2014). We aim to further describe the heterogeneous phenotypic pictures of SCN8A-related epilepsy.Methods: We used sequence analysis of the SCN8A gene in more than seven under patients with epileptic encephalopathy. In addition, we ascertained cases with SCN8A mutations from other centers. We compared the clinico-neurophysiologic data of patients with SCN8A-mutation. The patients underwent clinical evaluation, based on personal interviews and patients’ charts, neurophysiological and standard neuroradiological investigations. Neurophysiological studies included standard EEG and video-EEG-polygraphy during wakefulness and sleep.Results: Thirty-five patients with de novo heterozygous SCN8A mutations have been studied. They were either sporadic or familial cases. Based on their phenotype, we identified three different clinico-neurophysiologic subtypes: Sporadic patients with de novo heterozygous mutations of SCN8A, presenting with early onset severe drug resistant epilepsy, cognitive deterioration, pyramidal/extra-pyramidal signs and SUDEP (ca.12% of this cases). Patients had both generalized and focal prolonged seizures, with prominent hypomotor and vegetative symptoms, evolving to secondary generalization. EEG showed progressive background deterioration with epileptic abnormalities predominant in the posterior regions. Sporadic patients with de novo heterozygous mutations of SCN8A, presenting with mild to moderate intellectual disability, mild or none neurological signs and drug resistant epilepsy with extended seizure-free periods. EEG showed multifocal epileptiform abnormalities. Interestingly, three unrelated families with the same SCN8A missense mutation presented with a very mild form of epilepsy, remitting before puberty, and not associated with any cognitive or neurological deficit. Interictal EEG was either normal or showed not specific diffuse abnormalities in all adult affected members.Conclusions: We provide new data that further enlarge the phenotypic spectrum of SCN8A-related epilepsy including familial and sporadic cases, ranging from severe early onset encephalopathy with epilepsy, milder form of drug resistant epilepsy to familial cases with a very mild form of epilepsy.