A disease concept model for STXBP1-related disorders

Area of Science:

• Genetics and Neurology
• Rare Diseases Research
• Patient-Reported Outcomes

Background:

• STXBP1-related disorders are rare genetic conditions impacting neurodevelopment and causing epilepsy.
• The full spectrum of symptoms and their impact on individuals and families is not well understood.
• Disease concept models are crucial for assessing lived experiences and developing outcome measures.

Purpose of the Study:

• To comprehensively map the symptoms and impacts of STXBP1-related disorders.
• To develop a disease concept model for STXBP1-related disorders.
• To inform the development of clinical endpoints for future research and trials.

Main Methods:

• Conducted semistructured qualitative interviews with 19 caregivers and 7 healthcare professionals.
• Systematically coded interview themes using NVivo software.
• Grouped concepts into symptom, symptom impact, and caregiver impact domains, quantifying frequency across the lifespan and clinical subgroups.

Main Results:

• Identified 38 distinct concepts from over 25 hours of interviews, with 3626 references.
• Beyond known features like developmental delay, behavior, and seizures, underrepresented symptoms included gastrointestinal issues (n=68), respiratory symptoms (n=24), and pain (n=30).
• Key symptom impacts involved autonomy, socialization, and schooling; caregiver impacts centered on emotional well-being, support, and daily activities.

Conclusions:

• STXBP1-related disorders present a complex array of clinical and social challenges.
• The study generated a comprehensive disease model by mapping symptoms and their familial impact.
• This model serves as a foundation for defining clinical endpoints in future STXBP1-related disorder trials.