Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where affected individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravets syndrome, borderline SMEI (SMEB), and intractable  epilepsy of childhood (IEC). There are at least six types of GEFS+, delineated by their causative gene. Known causative gene mutations are in the sodium channel α subunit genes SCN1A, an associated β subunit SCN1B, and in a GABAA receptor γ subunit gene, in GABRG2 and there is another gene related with calcium channel the PCDH19 which is also known as Epilepsy Female with Mental Retardation. Penetrance for this disorder is estimated at 60%. Signs and symptoms
Individuals with GEFS+ present with a range of epilepsy phenotypes. These include febrile seizures that end by age 6 (FS), such seizures extending beyond age 6 that may include afebrile tonic-clonic, myoclonic, absence, atonic seizures and myoclonic-astatic epilepsy. Individuals may also present with SMEI, characterized by generally tonic-clonic seizures, impaired psychomotor development, myoclonic seizures, ataxia, and poor response to many anticonvulsants. Pathophysiology
Type 1
GEFS+ type 1 is a subtype of GEFS+ in which there are mutations in SCN1B, a gene encoding a sodium channel β subunit. The β subunit is required for proper channel inactivation. There are two known mutations in SCN1B that lead to GEFS+ (Figure 1). The first and best characterized of these mutations is C121W.
The result of this mutation is completely non-functional channels and membrane hypoexcitability. The truncated mutant protein also seems to cause wild-type channels to inactivate at more hyperpolarized potentials, indicating that it also acts in a dominant negative manner. Management
Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam. Ketogenic diet has also been found useful in certain cases Management of breakthrough seizures is by benzodiazepine such as midazolam. See also
Febrile seizures
Idiopathic generalized epilepsy
Dravet Syndrome Foundation
International Dravet Epilepsy Action League

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