Early mortality in STXBP1-related disorders

• DOI: 10.1007/s10072-024-07783-3
• Publication Date: 2024-10-11T13:01:54Z
• Authors: Francesca Furia; Charlene Son Rigby; Ingrid E. Scheffer; Nicholas Allen; Kate Baker; Christian Hengsbach; Josua Kegele; James Goss; Kathleen Gorman; Misra-Isrie Mala; Francesco Nicita; Talia Allan; Alberto Spalice; Yvonne Weber; ; Ganna Balagura; Bruria Benzeev; Hilgo Bruining; Alejandra Darling; Francesca Furia; Ángeles García Ca...; Misra-Isrie Mala; Mathieu Milh; Rikke Steensbjerr...; Hannah Stamberger; Pasquale Striano; Steffen Syrbe; Kim Marie Thalwitzer; Matthijs Verhage; Sarah Weckhuysen; ; Guido Rubboli; Rikke S. Møller; Elena Gardella
• Keywords: Male; Adult; Drug Resistant Epilepsy; Developmental and Epileptic Encephalopathy (DEE); Adolescent; Sudden Unexpected Death in Epilepsy/epidemiology; Infant; Middle Aged; Sudden unexpected death in epilepsy (SUDEP); Early mortality; Drug Resistant Epilepsy/genetics; Munc18 Proteins/genetics; Young Adult; Munc18 Proteins; Child, Preschool; STXBP1; Humans; Female; Registries; Human medicine; Sudden Unexpected Death in Epilepsy; Child; Preschool

Abstract Introduction Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs individuals with epilepsy DEE, sudden unexpected death (SUDEP) the major death. This study aimed to identify rate causes -related disorders. Methods Through an international call, we analyzed data on pathogenic variants, who passed away from related their disease. Results We estimated 3.2% (31/966), based Foundation Global Connect registry. In total, 40 (23 males) harboring collected different centers worldwide. They died at median age 13 years (range: 11 months—46 years). The most common was SUDEP (36%), followed by pulmonary infections respiratory complications (33%). incidence peaked mid-childhood, while non-SUDEP were more frequent early childhood or adulthood (p = 0.006). severe phenotypes, ( p 0.018). Conclusion found similar other DEEs, as well main These findings assist prognostic evaluation genetic counseling for families. help define implement preventative strategies.