Abstract

Generalised (or genetic) epilepsy with febrile seizures plus (GEFS+) is a syndrome caused by mutations in SCN1A and GABRG2 genes in 10% of families. Initially the GEFS+ phenotype was tightly defined, but the borders of both epilepsy within GEFS+ families and the epilepsy caused by SCN1A mutations are increasingly blurred. Eighty families were recruited for future genetic analysis. Characteristics were ascertained via semistructured interview and the pedigrees charted. Consensus as to whether families met the criteria for GEFS+ was achieved following debate within a team of two clinical research fellows, a genetics professor, a paediatric neurologist and a genetic counsellor. Fourteen families were classified as probable and ten as borderline GEFS+; in eight families GEFS+ was unlikely and 48 had another syndrome. Borderline GEFS+ had a greater mix of epilepsies than definite GEFS+, where idiopathic generalised epilepsy comprised 80% of diagnoses that persisted into adulthood (compared with 60%, p<0.01). Febrile seizures were reported twice as often in GEFS+ or GEFS+ borderline families (p<0.005) than “unlikely” families. Identifying families with either a classic or borderline phenotype has been important for efficient targeting of resources to inform gene discovery. Atypical febrile seizures were specific (97.5%, but not sensitive) for identifying GEFS+ or GEFS+ borderline families, where they accounted for 24 and 19% of febrile seizures respectively.