Brain, Vol 120, Issue 3 479-490, Copyright © 1997 by Oxford University Press
IE Scheffer and SF Berkovic
The clinical and genetic relationships of febrile seizures and the
generalized epilepsies are poorly understood. We ascertained a family with
genealogical information in 2000 individuals where there was an unusual
concentration of individuals with febrile seizures and generalized epilepsy
in one part of the pedigree. We first clarified complex consanguineous
relationships in earlier generations and then systematically studied the
epilepsy phenotypes in affected individuals. In one branch (core family) 25
individuals over four generations were affected. The commonest phenotype,
denoted as 'febrile seizures plus' (FS+), comprised childhood onset (median
1 year) of multiple febrile seizures, but unlike the typical febrile
convulsion syndrome, attacks with fever continued beyond 6 years, or
afebrile seizures occurred. Seizures usually ceased by mid childhood
(median 11 years). Other phenotypes included FS+ and absences, FS+ and
myoclonic seizures, FS+ and atonic seizures, and the most severely affected
individual had myoclonic-astatic epilepsy (MAE). The pattern of inheritance
was autosomal dominant. The large variation in generalized epilepsy
phenotypes was not explained by acquired factors. Analysis of this large
family and critical review of the literature led to the concept of a
genetic epilepsy syndrome termed generalized epilepsy with febrile seizures
plus (GEFS+). GEFS+ has a spectrum of phenotypes including febrile
seizures, FS+ and the less common MAE. Recognition of GEFS+ explains the
epilepsy phenotypes of previously poorly understood benign childhood
generalized epilepsies. In individual patients the inherited nature of
GEFS+ may be overlooked. Molecular genetic study of such large families
should allow identification of genes relevant to febrile seizures and
generalized epilepsies.
ARTICLES
Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes
Department of Neurology, Austin and Repatriation Medical Centre, Royal Children's Hospital, Melbourne, Australia.
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