Abstracts

Rationale: SCN2A-related disorders are rare neurodevelopmental conditions caused by pathogenic variants in the SCN2A gene. While seizure control is a common therapeutic endpoint, emerging evidence suggests a broader phenotypic spectrum requiring deeper understanding. The Dragonfly Study was launched in 2024 by the FamilieSCN2A Foundation in collaboration with the National Organization for Rare Disorders to longitudinally capture real-world data from individuals with SCN2A variants. This registry aims to identify evolving clinical features, assess treatment effectiveness, and support the development of novel therapeutics beyond seizure control.

Methods: The Dragonfly Registry is a global, patient-reported, longitudinal natural history study hosted on the IAmRare platform. Caregivers of individuals with confirmed SCN2A variants complete structured survey modules covering demographics, genetic findings, clinical milestones, comorbidities, medication use, and treatment outcomes. Participants are encouraged to update data every six months. Deidentified, aggregated data is made accessible to participants and will be shared with researchers. As of early 2025, over 150 individuals have been enrolled.

Results:

Initial analyses of the first 150 enrollees reveal:

• Median age of SCN2A diagnosis is ~2 years, ranging from infancy to adulthood.

• Communication and learning challenges are the most prevalent features, surpassing seizures in frequency.

• Fewer than half of participants report seizures, yet seizure control remains a primary clinical trial endpoint.

• Detailed parent-reported efficacy data for antiseizure medications suggest differential response, underscoring the potential for genotype-based treatment stratification.

• Milestone data across motor, cognitive, social, and communication domains demonstrate a wide but continuous distribution of developmental capabilities.

• Early findings indicate that areas like GI symptoms and motor deficits may merit more clinical and research attention.

Conclusions: The Dragonfly Study is a family-powered longitudinal registry capturing the diverse phenotypes and treatment experiences of individuals with SCN2A-related disorders. Preliminary data highlight the need for broader clinical trial endpoints and suggest that a shift beyond seizure-centric measures is warranted. Ongoing data collection and future analyses—especially those stratified by variant function—are expected to inform clinical practice, guide therapeutic development, and support more individualized treatment strategies.

Funding: This study was supported by a grant from the National Organization for Rare Disorders and through funding provided by the FamilieSCN2A Foundation.