The Pathogenesis of Febrile Seizures: An Update

Abstract

Febrile seizures(FS)is a specific epilepsy syndrome induced by fervescence in childhood,and it has been suspected to have a genetic basis.KCNQ2 and KCNQ3 genetic mutations related to benign familial neonatal convulsions(BFNC) have been confirmed, and mutations associated with generalized epilepsy with febrile seizure plus(GEFS+)were identified in SCN1A?SCN2A?SCN1B and GABRG2 genes. But the penetrance of FS and GEFS+ are incomplete and the clinical expression are very heterogeneous, suggesting that modifying genes and/or environmental factors strongly affect the phenotype.So the effects of temperature on ion channels associated with GEFS+ and FS are attracting increasing attention. Previous study has suggested that interleukin‐1β, a pyrogenic proinflammatory cytokine,is involved in the generation of febrile seizures or enhanced seizure susceptibility in animals, also recent research has been shown a mutation in the GABAA receptor subunit GABRG2 gene causing a temperature‐dependent intracellular trafficking defect‐misfolding and impaired assembly and ER retention, increased degradation, or rapid endocytosis would be worsened by fever resulting in febrile seizures.Moreover,our previous simulation studies have been shown that there is an obvious conformational change of M channel at 40?compared with that at 37?, and the fact that considerable temperature sensitivity in KCNQ2/KCNQ3 potassium channel has been verified.The intracellular trafficking defect of channel proteins caused by elevated temperature provides a new insight into the molecular pathomechanism of FS .