Abstracts

Rationale: Two families with Generalized Epilepsy with Febrile Seizures Plus (GEFS+) have been described with SCN1B mutation. GEFS+ is characterised by heterogeneous epilepsy phenotypes including Febrile Seizures (FS), Febrile Seizures (FS+), generalized epilepsies and rarely partial epilepsy, including temporal lobe epilepsy (TLE). TLE has generally been regarded as a sequelae of FS in individuals with hippocampal sclerosis (HS). Here we describe a family with autosomal dominant inheritance of TLE and GEFS+. Methods: Characterisation of epilepsy phenotypes in all family members was performed. Magnetic resonance imaging including hippocampal volumes and spectroscopy was used to determine hippocampal damage. Molecular genetic analysis included single strand conformation analysis and direct sequencing of SCN1B. Results: The family contained 6 affected individuals over 3 generations; 5 had FS or FS+, and 3 had TLE. Of the individuals with TLE, 1 had bilateral HS following recurrent febrile status epilepticus, 1 with FS had normal MRI and hippocampal volumes with abnormal right hippocampal spectroscopy, and 1, who had not had FS or FS+, had normal MRI and HC volumes (MRS was not performed). All 6 affected individuals had the same SCN1B mutation previously reported as did the unaffected British grandfather. Haplotypes differed from the previously described families indicating absence of a founder effect. Conclusion: A family with autosomal dominant GEFS+ and TLE is associated with the SCN1B mutation suggesting that TLE without preceding FS/FS+ can be a phenotype of GEFS+. The striking frequency of TLE in this family is unusual and implicates the presence of second gene predisposing to TLE.