Phenotypes of SCN9A mutations include febrile seizures (FS), genetic epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS), which pose challenges in clinical treatment.
DS cases without SCN1A mutation inherited have predicted SCN9A susceptibility variants, which may contribute to complex inheritance for these unexplained cases of DS.
Six of these Dravet syndrome patients with SCN9A missense variants also harbored either missense or splice site SCN1A mutations and three had no SCN1A mutations.
These channelopathies include genes encoding voltage-gated channels specific for sodium (SCN1A, SCN2A, SCN1B, SCN9A) and potassium (KCNQ2, KCNQ3) which account for a variety of epilepsy phenotypes ranging from mild, such as Benign familial neonatal seizures (BFNS) to severe, such as Dravet syndrome (severe myoclonic epilepsy of infancy, SMEI) and the rare and unusual syndrome paroxysmal extreme pain disorder (PEPD).