Idiopathic epileptic seizures and syndromes in infancy

A Core Group of the Task Force on Classification and Terminology has evaluated the lists of epileptic seizure types and epilepsy syndromes approved by the General Assembly in Buenos Aires in 2001, and considered possible alternative systems of classification. No new classification has as yet been proposed. Because the 1981 classification of epileptic seizure types, and the 1989 classification of epilepsy syndromes and epilepsies are generally accepted and workable, they will not be discarded unless, and until, clearly better classifications have been devised, although periodic modifications to the current classifications may be suggested. At this time, however, the Core Group has focused on establishing scientifically rigorous criteria for identification of specific epileptic seizure types and specific epilepsy syndromes as unique diagnostic entities, and is considering an evidence-based approach. The short-term goal is to present a list of seizure types and syndromes to the ILAE Executive Committee for approval as testable working hypotheses, subject to verification, falsification, and revision. This report represents completion of this work. If sufficient evidence subsequently becomes available to disprove any hypothesis, the seizure type or syndrome will be reevaluated and revised or discarded, with Executive Committee approval. The recognition of specific seizure types and syndromes, as well as any change in classification of seizure types and syndromes, therefore, will continue to be an ongoing dynamic process. A major purpose of this approach is to identify research necessary to clarify remaining issues of uncertainty, and to pave the way for new classifications.

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.