GABA A receptor epilepsy mutations

Idiopathic generalized epilepsy (IGE) syndromes are diseases that are characterized by absence, myoclonic, and/or primary generalized tonic-clonic seizures in the absence of structural brain abnormalities. Although it was long hypothesized that IGE had a genetic basis, only recently have causative genes been identified. Here we review mutations in the GABA A receptor α1, γ2, and δ subunits that have been associated with different IGE syndromes. These mutations affect GABA A receptor gating, expression, and/or trafficking of the receptor to the cell surface, all pathophysiological mechanisms that result in neuronal disinhibition and thus predispose affected patients to seizures.