Clinical and genetic characteristics of children with STXBP1 encephalopathy

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.