Description

Scientific background

Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant epilepsy syndrome with wide phenotypic variability within the same family. It is characterized by febrile seizures occurring even after the age of six and fever-independent generalized tonic-clonic epilepsy that may be associated with absences, myoclonic, atonic, or focal seizures.

Pathogenic variants in the SCN1A gene are the most common cause of GEFS+ accounting for 10-20%. SCN1A encodes the alpha1 subunit of a neuronal sodium channel. Variants are generally amino acid exchanges in the SCN1A gene which can result in both severe myoclonic epilepsy of early infancy (SMEI) and GEFS+. However, missense variants in the pore region of the sodium channel are more commonly associated with severe SMEI. In addition, variants in other genes have also been described in GEFS+. These include genes of neuronal voltage-gated sodium channels (SCN1B, SCN2A, SCN9A) or for subunits of the GABA receptor (GABRG2 and GABRD).

References

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