Prevalence
Unknown but possibly high considering the increasing numbers of publications and the broad spectrum of GEFS+.

Age at onset
The age at onset, from the first months of life to childhood, varies considerably among patients, even individuals of the same family. Febrile seizures start earlier (median 1 year) than the typical febrile seizures; they are often multiple and continue beyond 6 years.

Sex
Males = females.

Neurological and mental state
Normal.

Etiology
Purely genetic disorder with profound heterogeneity. Inheritance is generally autosomal dominant with incomplete penetrance, but this may not be the only situation. Two loci are on chromosome 19q (GEFS+) and chromosome 2q (GEFS2). Mutations were found in voltage-gated sodium channel subunits and GABAA–receptor gamma 2 subunit. Seizure predisposition determined by the GEFS+ genes probably modified by other genes and environmental factors.

Clinical manifestations
Febrile seizures plus (FS+) comprise childhood onset of multiple febrile seizures that (unlike the typical febrile seizure) continue beyond the age of 6 years.

The syndrome of GEFS+ is characterized by the presence of febrile and heterogeneous non-febrile seizures. There is a variety of clinical phenotypes, including typical febrile seizures (49%), FS+ (24%), and other seizure types (13%) such as absences, myoclonic or atonic seizures, and focal seizures. Absences are infrequent and unlike those of childhood absence epilepsy (CAE). Dravet syndrome probably represents the very severe end of the spectrum within the GEFS+ phenotype. Myoclonic astatic seizures such as those of Doose syndrome (epilepsy with myoclonic astatic seizures) occur in 14%.

Inter-ictal EEG
Usually normal background with generalized discharges.

Ictal EEG
Depends on seizure type.

Prognosis
Seizures usually remit by mid-childhood (median 11 years). Development is usually normal.

Differential diagnosis
Febrile seizures. The evolution to severe clinical phenotypes such as epilepsy with myoclonic astatic seizures (EM-AS) or Dravet syndrome becomes apparent only with the emergence of new types of seizures compatible with these disorders.

Management options*
Repetitive febrile seizures or FS+ may need prophylactic treatment. Valproate, lamotrigine, levetiracetam, or topiramate may be used for non-febrile generalized seizures, if these are frequent.

*Expert opinion, please check FDA-approved indications and prescribing information

This section was adapted from:

The educational kit on epilepsies: The epileptic syndromes By C. P. Panayiotopoulos Originally published by MEDICINAE, 21 Cave Street, Oxford OX4 1BA
First published 2006 and reprinted in 2007. The Educational Kit on Epilepsies was produced through an unrestricted educational grant from UCB Pharma SA.
UCB Pharma SA assumes no responsibility of the views expressed and recommended treatments in these volumes.

Authored by: C. P. Panayiotopoulos MD PhD FRCP on 1/2005
Reviewed by: Steven C. Schachter MD on 6/2008
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