The phenotypic variability associated with sodium channel alpha 1 subunit gene SCN1A mutations was studied in 188 patients with various infantile epileptic encephalopathies referred to the Universities of Adelaide and Melbourne, Australia; and centres in Glasgow, UK; Wellington, New Zealand; Montreal and Vancouver, Canada; Worcester, MD, USA, Israel, and Denmark. All had seizure onset within the first 2 years of life. The total cohort contained 66 with severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome), 36 had SMEI-borderland (SMEB), a syndrome that lacks myoclonic seizures or generalized spike-wave activity, 25 with cryptogenic generalized epilepsy, 18 with cryptogenic focal epilepsy, 10 with myoclonic-astatic epilepsy (MAE), and 12 with Lennox Gastaut syndrome (LAS). By molecular analysis, 90 (48%) had SCN1A mutations; 52 of the 66 (79%) patients with SMEI and 25 of 36 (69%) with SMEB had SCN1A mutations. Mutations were present in 24% of patients with cryptogenic generalized epilepsy and 22% of those with cryptogenic focal epilepsy. A small subgroup of 5 cases of severe infantile multifocal epilepsy (early onset seizures and later cognitive decline) had SCN1A mutations in 3. This broadening of the phenotypic spectrum of infantile epileptic encephalopathies allows early molecular diagnosis and genetic counseling. [1]

COMMENT. SMEI or Dravet syndrome is characterized by prolonged febrile hemiclonic or generalized tonic-clonic seizures with onset in the first year of life. Myoclonic, focal, absence and atonic seizures evolve between 1 and 4 years, and are accompanied by slow development and regression. Neurologic abnormalities include spasticity and ataxia. Some survive into adulthood, but seizures are refractory, and cognitive outcome is poor (cited by authors) [2]. In the current report, infantile.epileptic encephalopathies with SCN1A mutations now include, in addition to SMEI and SMEB, several infantile onset epileptic syndromes, previously thought to be cryptogenic.