Generalised Epilepsy With Febrile Seizures Plus, GEFS+ - SCN1A, SCN1B, SCN2A, GABRD, GABRG2

Clinical Features

GEFS+ type epilepsies comprise a wide clinical spectrum of epilepsies that can vary greatly in manifestation and severity, even within a single family.
The primary symptom is multiple febrile seizures in childhood, even continuing past 6 years of age. Some patients develop additional afebrile seizures. Seizures can be generalized (tonic-clonic, myoclonic, atonic, absence) or partial. In some cases, affected patients develop classic, temporal lobe epilepsy only in adulthood; it is therefore necessary to include all affected family members in a diagnosis.
Mutations in the SCN2A gene can also cause BFNIS Syndrome (benign familial neonatal infantile seizures); Childhood Absence Epilepsy (CAE) has been associated with mutations in the GABRG2 gene.

Genetic Information

The underlying genetics are very heterogeneous; as a rule, the pattern of inheritance is autosomal dominant. Mutations are most often found in the SCN1A gene (2q24, Sodium channel protein type 1 subunit alpha, 10% of cases). Mutations in the SCN2A (2q24.3, Sodium channel protein type 1 subunit beta), SCN1B (19q13.1, Sodium channel protein type 2 subunit alpha), GABRG2 (5q34, Gamma-Aminobutyric Acid Receptor, GAMMA-2) and GABRD (1p36.33, Gamma-Aminobutyric Acid Receptor, Delta) genes are less common.
Epilepsies caused by mutations in the SCN1A gene follow an autosomal dominant pattern of inheritance and have incomplete penetrance. New mutations are possible, especially in severe forms of the disease.