Abstracts

Rationale: Channelopathies have emerged as an important mechanism underlying several epilepsies including autosomal dominant nocturnal frontal lobe epilepsy(ADNFLE), benign familial neonatal convulsions (BFNC), generalized epilepsy with febrile seizures plus (GEFS+), and severe myoclonic epilepsy of infancy/Dravet syndrome, in which a sodium channel gene mutation (SCN1A) has been described. Dravet syndrome is associated with intractable epilepsy, epileptic encephalopathy, and mental retardation for most children. SCN1A encodes a neuronal voltage-gated sodium channel alpha 1 subunit protein. Mutations in SCN1A are associated with a spectrum of epilepsy phenotypes, including GEFS+ and two severe forms seen in infants. We report the clinical features and molecular genetic testing results of six children with Dravet syndrome. Methods: Six children with a clinical profile suggestive of Dravet syndrome had positive genetic test results; three of them had novel mutations. Results: See Table I: Clinical and EEG Characteristics of Children with SCN1A Mutation Conclusions: Dravet syndrome is the first channelopathy associated with refractory epilepsy and epileptic encephalopathy. This epileptic syndrome is highly associated with poor cognitive outcome and thus provides a model for studying the effects of seizures on the developing brain. Understanding the molecular basis can lead to novel treatments and in turn provide insight into the effects of seizure control on developmental outcome. For patients who follow the clinical evolution from prolonged febrile episodes in infancy to mixed seizure types, developmental regression, a deterioration of the EEG and refractory seizures in early childhood, testing for SCN1A is indicated, and testing should be considered in other idiopathic childhood epileptic encephalopathies.