Genetic analysis of Ohtahara syndrome and atypical benign partial epilepsy coexisting in a family

Abstract

Objective To explore the genetic etiologies in 2 siblings with different epileptic encephalopathies (EEs) diagnosed as Ohtahara syndrome(OS) and atypical benign partial epilepsy(ABPE) from one family. Methods The 2 brothers were diagnosed at the Pediatric Neurological Clinic of Peking University First Hospital in September 2013, whose clinical data were collected.The coding region of the syntaxin-binding protein 1 gene (STXBP1) and glutamate receptor subunit gene (GRIN2A) were detected by using Sanger sequencing in the 2 siblings.For the elder brother, targeted next-generation sequencing was further performed to detect the genes associated with epilepsy. Results The younger brother manifested focal motor seizures and tonic spasms in cluster at the age of 1 month.Interictal electroencephalogram (EEG) showed suppression-burst pattern.He was diagnosed as OS.The elder brother had seizure onset at age of 6 years old.Focal motor seizure during sleep was his seizure type.His EEG showed interictal discharges in Rolandic area primarily.Electrical status epilepticus during sleep, epileptic negative myoclonus and intellectual disabilities occurred during the course.He was diagnosed as ABPE.Brain magnetic resonance imagines for both of them were normal.Screening of STXBP1 mutations for the younger brother found a de novo heterozygous mutation: c.1672C>T (p.Q558X). Gene detection for the elder brother and the parents showed negative results. Conclusions Coexistence of distinct EEs was reported in 2 brother siblings: the younger brother had OS associated with a novel nonsense mutation in STXBP1, and the elder brother had ABPE without genetic evidence.This study indicated that different pathological mechanisms might exist underlying the two different EEs in a family. Key words: Epileptic encephalopathy; Ohtahara syndrome; Siblings; Syntaxin-binding protein 1 gene; Glutamate receptor subunit gene