SCN1A and epilepsy: The unified loss-of-function hypothesis proposes that mild impairment of Nav1.1 function results in febrile seizures, moderate loss of function results in generalized epilepsy with febrile seizures plus epilepsy, and severe functional impairment results in refractory epilepsy and severe myoclonic epilepsy of infancy comorbidities (Catterall et al., 2010).