Phenotypic variability of GABRA1‐related epilepsy in monozygotic twins

Abstract

Abstract Variants in GABRA1 have been associated with different epilepsies ranging from mild generalized forms to epileptic encephalopathies. Despite the broad clinical spectrum, phenotypes were found to be largely concordant within families. Contrary to this observation, we report monozygotic twin sisters with generalized epilepsy due to the c.541C>T; p.(Pro181Ser) de novo variant in GABRA1. One experienced juvenile absence seizures promptly responding to first‐line medication, whereas the second developed severe treatment‐refractory epilepsy with febrile, absence, atonic, and tonic‐clonic seizures indicating marked intrafamilial variability in GABRA1‐related epilepsy. Moreover, we provide a molecular characterization of the novel variant based on recently published structural data.