Abstract:

Objective To investigate the clinical phenotype and genetic characteristics of children with developmental and epileptic encephalopathy(DEE) caused by syntaxin-binding protein 1(STXBP1) gene mutation. Methods The clinical data of 11 patient with STXBP1 gene-related encephalopathy admitted to the Third Affiliated Hospital of Zhengzhou University from October 2015 to May 2022 were retrospectively reviewed, and their clinical phenotypes, gene outcomes, treatment and efficacy were analyzed. Results Of the 11 children, 4 were males and 7 were females, 10 had seizures with developmental delay and 1 showed only developmental delay. The age of onset of epilepsy was 3 days to 1.5 years, with 6 cases starting at less than 3 months, 3 at 3-12 months, and 1 at more than 1 year of age. The common seizure types are epileptic spasm and focal seizure. All the 11 patients had the abnormal interictal electroencephalograms (EEG) including background slowness, multifocal discharge, suppression-burst, and hypsarrhythmia. Two cases had Otahara syndrome in the early stages, which evolved into infantile spasms in the later stages, five cases had infantile spasms, and the rest had epileptic syndromes that could not be typed. Four children had non-specific abnormalities on cranial MRI, including poor development of myelination, and widening of the subarachnoid space in the frontotemporal region.frontotemporal. All children had STXBP1 gene variants, with a total of 11 variant types, including 7 missense variants, 1 frameshift variant, 1 splicing variant, and 2 deletion variants, and the variant loci of the 7 children have not been reported in the literature, which were c.1694T>A, c.1115T>G, C.133_135del, C.1543dupG, exons 6-17 heterozygous deletion, C.429+1G>C, C.855C>G and c.842_843insGGACGACGGCCTGTGGGATAGCACT. During follow-up, 11patients had different degrees of developmental delay, 2 patients had died, and 4 patients had autistic like features. Ten patients with epilepsy were treated with levetiracetam. One patient was seizure free with levetiracetam alone, 5 patients showed partial response, and 4 patients showed no response on multitherapy. 3 patients was seizure free, the remaining 7 patients were drug resistant epilepsy. Conclusion STXBP1 gene-related epilepsy usually occur to infant, and infantile spasm is the most common phenotype. There is significant heterogeneity in the therapeutic effect of epilepsy. Seven unreported mutation sites enriched the gene spectrum of STXBP1 encephalopathy.

Key words: STXBP1 gene, developmental epileptic encephalopathy, developmental delay