Abstracts

We report the clinical and genetic study of a large French family with febrile seizures (FS) and childhood absence epilepsy (CAE)., This family was identified through a national French campaign for familial epilepsy. It spans 4 generations and consists of 51 members with 13 affected. The medical history of all members was obtained by personal information and by consulting the medical files of each affected member. All family members gave a written consent to participate and 26 DNA were available for genetic study., Clinical study: All affected members presented FS with CAE in 5 members and TLE in one. All FS stopped before the age of 6 and they recurred less than 4 times. Patients presenting CAE had recorded absences and characteristic EEG with 3 Hz spike waves. FS were simple except in one patient who had a long lasting complex FS (45 minutes) that occurred at 8 months of age. He presented later pharmaco-resistant TLE. He had a left hippocampal sclerosis on brain MRI. All family members have a normal psychomotor development.Genetic study: The FS trait segregates as autosomal dominant trait. The genetic study allowed the exclusion of any linkage with reported loci for FS and FS plus (FS+), especially with the locus of GABRG2 gene on chromosome 5q reported in a family presenting FS+ and absences. A genome wide search with 380 markers allowed us to localize a new gene responsible for FS on 3p. We could not exclude another genomic segment with positive Lodscore (Z=1.94 at [theta]=0.00). All patients presenting further epilepsy (CAE and TLE) shared a common haplotype on this locus in addition to the FS haplotype on 3p., These findings emphasize the genetic heterogeneity of FS. Epilepsy in association with FS could result in this family from an interaction between at least 2 genes: the gene on 3p with a modifier gene., (Supported by ARGE, FFRE.)