Haploinsufficiency of STXBP1 and Ohtahara Syndrome

Abstract

Abstract Ohtahara syndrome (OS), also known as early infantile epileptic encephalopathy with suppression-burst, is one of the most severe and earliest forms of epilepsy.1 It is characterized by early onset of tonic seizures, seizure intractability, characteristic suppression-burst patterns on the electroencephalogram (EEG), and a poor outcome with severe psychomotor retardation.2,3 Brain malformations, such as cerebral dysgenesis or hemimegalencephaly, are often associated with OS, but cryptogenic or idiopathic OS is found in a subset of OS patients, in whom genetic aberrations might be involved.4 Although mutations of the ARX gene have been found in several male patients with OS,5–8 the genetic causes are unexplained in most cryptogenic OS cases. We have recently found de novo mutations in STXBP1 (encoding syntaxin binding protein 1, also known as MUNC18-1) in individuals with cryptogenic OS.9 Here we present all the mutations in STXBP1 found to date in OS patients, as well as some evidence of mutations leading to haploinsufficiency.