Abstracts

Mutations in the sodium channel alpha 1 subunit gene [italic] SCN1A [/italic] underlie about 70% of cases of Severe Myoclonic Epilepsy of Infancy (SMEI or Dravet syndrome) and around 50% cases of Borderline SMEI (SMEB). We hypothesized that the phenotypic variability of [italic] SCN1A [/italic] mutations was broader and we studied individuals with a severe epileptic encephalopathy beginning early in life., 205 patients with severe epileptic encephalopathies underwent detailed phenotyping. [italic] SCN1A [/italic] was examined by denaturing high performance liquid chromatography for sequence variations. DNA changes were characterized by automated DNA sequence analysis., [italic] SCN1A [/italic] mutations were found in 79% SMEI (n=66) and 69% SMEB (n=36) patients consistent with previous studies. We identified [italic] SCN1A [/italic] mutations in 3/6 patients with a distinctive new entity characterized by: early onset multifocal seizures (onset under 1 year of age), abundant multifocal epileptiform discharges, absence of generalized spike wave activity, normal or nonspecific MRI brain findings, and in some cases, later cognitive decline at 3-6 years. This new phenotype was coined Severe Infantile Multi-Focal Epilepsy., We have expanded the phenotypic spectrum of [italic] SCN1A [/italic] mutations to include a new epileptic encephalopathy with severe multifocal rather than generalized epilepsy, cognitive decline and poor outcome. We have shown that focal epilepsies previously regarded as cryptogenic may be due to [italic] SCN1A [/italic] mutations. Molecular diagnosis enables patients to avoid invasive investigations looking for alternate etiologies, allows optimal choice of therapy and has genetic counseling implications., (Supported by grants from the NHMRC, Bionomics Ltd and a donation from the Thyne-Reid Charitable Trusts.)