Linkage analysis was conducted in 5 French families with generalized epilepsy with febrile seizures plus (GEFS+), with at least 7 affected members with autosomal dominant transmission, in an attempt to localize a new gene for GEFS+, at Hospitalier Pitie-Salpetriere, Paris, France. In the largest family with 11 affected members, a sixth locus for GEFS+ was revealed on chromosome 8p23-p21. A second family was also possibly linked to the same chromosome. The responsible gene has not been identified. Most patients in the 5 families had simple FS (93%) and some had afebrile seizures (34%), mainly generalized tonic clonic or absence seizures. None of the families were linked to previously reported GEFS+ and FS loci. 
COMMENT. GEFS+ is inherited as an autosomal dominant trait with incomplete penetrance, and is characterized by the association of febrile and afebrile seizures. GEFS+ is genetically heterogeneous, and has been linked to chromosome 2q21 (SCN1A), 19ql3 (SCN1B), and 5q34 (GABRG2). Links to 2p24 and 21q22 are more recent reports. The above novel locus, the 6th to be identified for GEFS+, is located on chromosome 8p23-p21. Patients with linkage to 8p23-p21 have a high familial FS occurrence, a high rate of recurrence of FS, a tendency to complex FS, and frequent afebrile seizures.