Phenotypic and genotypic characteristics of children STXBP1-related disorders

STXBP1 mutations are a leading genetic cause of neurodevelopmental disorders. This study seeks to clarify the clinical features and explore the genotypes and phenotypes of children with STXBP1-related conditions.

We conducted a thorough analysis of medical histories, MRI findings, video-EEG recordings, and genetic data from patients with STXBP1-related disorders at Beijing Children's Hospital from 2017 to 2024.

The study included 28 children with STXBP1 variants (13 girls and 15 boys). Of these, 24 had developmental and epileptic encephalopathy (DEE), while 4 (Patients 11, 13, 23, and 27) had developmental delay without seizures. Sixteen patients experienced a single seizure type, and 8 had multiple types. The most common seizures were focal to bilateral tonic-clonic seizures (FBTCS), generalized tonic-clonic seizures (GTCS), and epileptic spasms (ES).Among the cohort of 28 patients, 27 individuals (96.4%) exhibited developmental delays. Of these, 14 patients demonstrated severely impaired intellectual functioning. All patients in the study were found to have de novo mutations in the STXBP1 gene. The identified genetic variants included 1 start coden mutation, 2 nonsense mutation, 3 deletion variants, 6 splice-site alterations, and 13 missense mutations. Seizure control was achieved in 14 patients and seven patients have had drug-resistant epilepsy. Regrettably, 3 patients succumbed to sudden unexpected death in epilepsy (SUDEP).

This study broadened the spectrum of STXBP1-related disorders and enhanced the comprehension of the associated phenotypic variability. The severity of phenotypes in patients with STXBP1-related developmental and epileptic encephalopathy (STXBP1-DEE) varied from drug-responsive seizures to refractory epilepsy. A significant proportion of individuals exhibited developmental delay. Additionally, three cases (10.7%) of sudden unexpected death in epilepsy (SUDEP) were reported.