Mrabet et al. (2007) investigated whether the commonly described mutations of the SCN1A, SCN1B and GABRG2 genes might be associated with generalized epilepsy with febrile seizure plus (GEFS+) in two unrelated multigenerational Tunisian families affected with GEFS+ spectrum. Information was obtained on 91 individuals from the two families; 26 individuals had epilepsy (14 males and 12 females), of whom 17 had a picture consistent with the GEFS+ spectrum, based on detailed clinical history of the patients themselves or of their relatives; 9 had unclassified epilepsies appearing in childhood and persisting till the adult age. Epilepsy phenotypes were determined for the 17 affected members. Nine patients had typical febrile seizures (FS) with median age at seizure onset was 8 months. Interictal EEG recordings were normal in most these patients. Fifteen patients had febrile seizures plus (FS+) with a median age at onset of 7 years. Six patients had typical FS associated to FS+. In addition to FS+, two patients had daily/weekly absence seizures. In one of the probands, this started at the age of 6. Neurological examination was normal. Video EEG monitoring recorded typical absence seizures with 3-Hz generalized SW discharges. In addition to FS+, another proband had, since the age of 2, nocturnal short seizures characterized by unresponsiveness, left deviation of the head and eyes and sometimes a secondary generalization. Neurological examination and brain MRI were normal. Sleep EEG recording revealed generalized SW and a right frontal focus. At the molecular level, a novel single insertion of a T nucleotide at a heterozygous state within the intron 12 of the SCN1A gene (IVS12-11insT) was identified in two probands and their parents and it can have a pathogenic role in the expression of the GEFS+ disease.

Fendri-Kriaa et al. (2010) conducted a genome-wide association study in a large Tunisian family with GEFS+. The highest multipoint logarithm of odds (LOD) score (1.04) was found for D5S407 in the absence of recombination. Two other interesting regions were found around marker D19S210 (LOD=0.799) and D7S484 (LOD=0.61) markers. Additional markers in two regions on 5q13.3 and 7p14.2 were analyzed and positive LOD scores for both loci were obtained.