Abstracts

Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare disorder occurring in patients without a family history of a similar disorder. Early manifestations of the disease are tonic, clonic and tonic-clonic seizures associated with fever occurring within the first year of life. Early psychomotor and speech development is normal, but in the second year of life developmental stagnation occurs. Patients often become ataxic. In general, SMEI is very resistant to all anti-epileptic drugs. A mild type of epilepsy associated with febrile and occasionally afebrile seizures in adulthood is generalized epilepsy with febrile seizures plus (GEFS+). Missense mutations in the gene coding for a neuronal voltage-gated sodium channel a-subunit (SCN1A) were identified in families with GEFS+. In 2001, we identified de novo mutations in SCN1A in 7 SMEI patients. Since our initial report, recognition of this rare syndrome has accelerated around the world, and more than 100 SCN1A mutations have been reported. We identified novel SCN1A mutations in SMEI patients using PCR sequencing. Interestingly, several mutations were inherited, and patients with the same SCN1A mutation present with different phenotypes. We give an overview of reported and novel mutations, an update on disease mechanisms and discuss the relationship between genotype and phenotype. (Supported by The Fund for Scientific Research Flanders (FWO) and the Interuniversity Attraction Poles (IUAP) program P5/19 of the Belgian Science Policy Office, Belgium.)