SCIENTIFIC BACKGROUND

ADGRV1, CPA6, GABRD, GABRG2, HCN1, PCDH19, PRRT2, SCN1A, SCN1B, SCN2A, SCN9A, STX1B

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 that continue 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 usually the result of amino acid exchanges in the SCN1A gene which can cause 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 for neuronal voltage-gated sodium channels (SCN1B, SCN2A, SCN9A) or for subunits of the GABA receptor (GABRG2 and GABRD).

 

References

Gerosa et al. 2019, Dev Neurobiol 79:75 / Liu et al. 2019, J Med Genet 56:81 / Smith et al. 2018, Epilepsia 59:679 / de Lange et al. 2017, Neurogenetics 18:147 / Duszyc et al. 2015, J Appl Genet 56:49 / Depienne et al. 2011, Hum Mutat 32:E1959 / Scheffer et al. 2009, Brain Dev 31:394 / Sun et al. 2008, J Hum Genet 53:769 / Wallace et al. 2001, Nat Genet 28:49 / Wallace et al. 1998, Nat Genet 19:366 / Scheffer and Bercovic 1997, Brain 120:479

GENES
ADGRV1, CPA6, GABRD, GABRG2, HCN1, PCDH19, PRRT2, SCN1A, SCN1B, SCN2A, SCN9A, STX1B
ASSOCIATED TESTS
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