Clinical and genotypic characteristics of 19 children with STXBP1-encephalopathy

To systematically summarize the clinical phenotypes, treatment responses, prognosis, and genetic characteristics of STXBP1-encephalopathy in Chinese pediatric patients, and to explore the clinical value of genetic testing in this disease. We retrospectively analyzed the clinical data, gene variant information, and treatment outcomes of 19 children with STXBP1-encephalopathy admitted to the Department of Pediatrics, Second Affiliated Hospital of Zhejiang University, between January 2020 and January 2024. Whole-exome sequencing was performed for genetic diagnosis, and Sanger sequencing was used to verify variants and confirm their parental origin. Pathogenicity of variants was classified according to the American College of Medical Genetics and Genomics guidelines. STXBP1-encephalopathy showed early onset, with 15 cases (78.9%) occurring within the 1st month of life. Five patients were diagnosed with Ohtahara syndrome, 5 with West syndrome, and 9 with unclassifiable early-onset epileptic encephalopathy. All patients had abnormal electro-encephalogram findings, mainly burst suppression (68.4%) and hypsarrhythmia (63.2%). Among the 19 patients, 1 achieved seizure freedom and discontinued antiepileptic drugs, and 4 achieved seizure control with levetiracetam. A total of 18 de novo pathogenic/likely pathogenic variants in STXBP1 were identified, including 7 novel variants: c.326-3(IVS5)delC, c.656del(p.Met219Argfs*13), c.746-747del(p.F249fs*6), c.798T > G(p.Y266*), c.1155delC(p.D385fs), c.1249G > A(p.G417S), and c.1250-2A > G. STXBP1 pathogenic variants are an important cause of early-onset developmental epileptic encephalopathy in Chinese children. Genetic testing is crucial for early diagnosis of STXBP1-encephalopathy. Levetiracetam shows good efficacy in controlling seizures in these patients, and early use is recommended. The 7 novel variants identified in this study expand the STXBP1 mutation spectrum.