Early mortality in STXBP1-related disorders

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Pathogenic variants in STXBP1 gene are linked to developmental and epileptic encephalopathy (DEE).
• DEE often presents with drug-resistant epilepsy, increasing mortality risk.
• Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in these patients.

Purpose of the Study:

• To determine the mortality rate in individuals with STXBP1 pathogenic variants.
• To identify the primary causes of death in STXBP1-related disorders.
• To aid in prognostic evaluation and genetic counseling for families.

Main Methods:

• International data collection from STXBP1 Foundation and Global Connect registry.
• Analysis of mortality data from individuals with pathogenic STXBP1 variants.
• Retrospective review of causes of death in affected individuals.

Main Results:

• An estimated mortality rate of 3.2% (31/966) was identified.
• Sudden unexpected death in epilepsy (SUDEP) accounted for 36% of deaths.
• Pulmonary infections and respiratory complications caused 33% of deaths, with SUDEP more common in mid-childhood.

Conclusions:

• Mortality rate in STXBP1 disorders is comparable to other DEEs.
• SUDEP and pulmonary infections are the leading causes of death.
• Findings support improved prognostic evaluation, genetic counseling, and preventative strategies.