Abstracts

Rationale: Mutations in the alpha 1 subunit of the voltage gated sodium channel (SCN1) have been identified in generalized epilepsy with febrile seizure (plus additional symptoms-GEFS+) and severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome). SMEI is characterized initially by normal development and febrile seizures followed by multiple seizure types and slowing of psychomotor development. The EEG is usually normal in the first year of life, but later generalized spikes, spike-wave or polyspike discharges are observed. These seizures are often refractory to anticonvulsants.Methods: We report a four-year old girl who, at six months of age, developed her first febrile convulsion with focal onset lasting 15-20 minutes. Subsequently, at 15 months, afebrile tonic-clonic and myoclonic seizures appeared. Etiologies including metabolic disorders and various types of progressive myoclonic epilepsy were excluded. The EEG showed frequent bilateral spike and wave, as well as polyspike and wave activity. Lamotrigine therapy resulted in an ataxic gait and no significant relief from seizures. Valproic acid treatment resulted in reasonable seizure control. As she grew older, she exhibited difficulty in social situations, lack of eye contact, and speech delay . Genetic testing for SCN1A revealed a novel heterozygous stop codon mutation (R701X) in exon 12.Results: N/AConclusions: The majority of patients with Dravet syndrome have de novo mutations in SCN1A gene on chromosome 2q24, which may lead to either a loss of function or dominant gain of function of this subunit. A genotype-phenotype correlation has been implicated for differences in clinical variants of both GEFS+ and SMEI syndromes. This case further illustrates the clinical and genetic heterogeneity of the SCN1A mutation and the importance of early recognition of this condition for choosing the most appropriate therapy.