Abstract:

Objective To investigate the genetic basis of a family with generalized epilepsy with febrile seizures plus (GEFS+) and to perform integrated genetic and clinical analysis. Methods Clinical data were collected from a pediatric patient presenting with febrile seizures and his family members who visited the Neurology Department of Women and Children's Hospital of Ningbo University in February 2022. Peripheral blood DNA was extracted from the proband, his sister, and their parents. Whole-exome sequencing (WES) was conducted to identify potential pathogenic gene variants, followed by real-time fluorescent quantitative polymerase chain reaction (qPCR) for validation and pathogenicity assessment of candidate variants. Relevant literature was also reviewed. Results Both the proband and his sister carried a heterozygous deletion spanning exons 8-9 and part of exon 10 of the STX1B gene (STX1B exon 8-9 del, exon 10 partial del), which was maternally inherited. The proband was a 2.5-year-old boy who presented with fever-associated convulsions characterized as generalized tonic-clonic seizures. Without treatment, he experienced one additional seizure during follow-up with similar features. His sister had a history of childhood febrile seizures and later developed epilepsy. She was treated with sodium valproate and levetiracetam over 5 years, resulting in seizure control, with no intellectual or motor impairments observed. The mother had a personal history of childhood febrile seizures and epilepsy, and remained seizure-free after discontinuation of antiepileptic drugs following a 3-year course. A comprehensive literature review identified 65 reported cases of STX1B-related epilepsy involving 34 distinct variant sites. Missense variants were most commonly reported. Clinical manifestations showed significant heterogeneity in seizure types, and prognosis varied depending on the specific variant. Conclusion This study identified a novel heterozygous deletion in the STX1B gene encompassing exons 8-9 and part of exon 10, which has not been previously described. Follow-up findings suggest that epilepsy associated with this newly identified variant responds well to antiepileptic drug therapy. Despite episodes of febrile seizures, no cognitive or neurological deficits were observed.

Key words: STX1B gene, febrile seizures, epilepsy, gene variation, genetics