Generalized Epilepsy With Febrile Seizures Plus, Type 6

For a general phenotypic description and a discussion of genetic heterogeneity of generalized epilepsy with febrile seizures plus (GEFS+), see 604233.

Clinical Features

Baulac et al. (2008) reported a large French family in which 11 individuals had at least 1 febrile seizure, 3 of whom also had afebrile seizures. In 4 patients, febrile seizures began at age 8 months to 1.5 years and persisted beyond age 6 years. Two individuals had complex febrile seizures with transitory hemiplegia. The 3 patients with afebrile seizures had generalized tonic-clonic seizures or absence seizures. All affected family members had normal psychomotor development. A second French family contained 11 individuals with febrile seizures, 7 of whom were available and alive at the time of the report. Six of the 7 patients had febrile seizures with onset between 9 and 24 months. All seizures stopped before age 6 years, except in 1 patient who had his last at age 8 years. Two patients also had absence epilepsy, with late childhood onset and a 3-Hz spike-wave pattern recorded by EEG. Three family members who died before the study had epilepsy without reported febrile seizures: one had absence epilepsy and the other 2 had temporal lobe seizures beginning in adolescence. Psychomotor development was normal in all affected family members.

Inheritance

The transmission pattern of GEFS+ in the families reported by Baulac et al. (2008) was consistent with autosomal dominant inheritance with reduced penetrance.

Mapping

By genomewide mapping of a large French family with GEFS+, Baulac et al. (2008) identified a candidate 13-Mb interval on chromosome 8p23-p21 that segregated with the disorder (maximum pairwise lod score of 3.00 for markers D8S351 and D8S550; multipoint lod score of 3.23). A second French family with GEFS+ was also possibly linked to chromosome 8p23-p21, and the region was narrowed to a 7.3-Mb candidate interval flanked by markers D8S1706 and D8S549. Sequence analysis excluded mutations in the coding exons of 6 candidate genes within the 7.3-Mb interval.