Journal article
Natural History of Children and Adolescents With Dravet Syndrome: A 24-Month Follow-Up
Neurology, Vol.105(11), e214388
12/09/2025
DOI: 10.1212/WNL.0000000000214388
PMCID: PMC12622971
PMID: 41237355
Abstract
Background and Objectives
Dravet syndrome (DS) is an intractable developmental and epileptic encephalopathy caused primarily by pathogenic variants in the voltage-gated sodium channel α subunit 1 (SCN1A) gene. Patients with DS experience refractory seizures and significant cognitive and behavioral deficits. Longitudinal studies using standardized assessments are needed to systematically document patient outcomes over time. The BUTTERFLY study aimed to assess changes in adaptive functioning and neurodevelopment over 24 months in patients with DS.
Methods
BUTTERFLY was a US-based multicenter, longitudinal observational study involving patients with genetically confirmed DS who were receiving standard-of-care treatment. Patients aged 2–18 years with a confirmed DS diagnosis were included. Exclusion criteria included gain-of-function SCN1A variants, current sodium channel blocker treatment, or other disorders per investigator discretion. The primary outcome measures—adaptive functioning and neurodevelopment—were assessed using Vineland Adaptive Behavior Scale, Third Edition (Vineland-3); Bayley Scales of Infant Development, Third Edition (BSID-III); and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Assessments were conducted at baseline and at 3, 6, 12, 18, and 24 months across 15 sites. Mixed models for repeated measures were used to analyze disease progression, and comparisons were made with published standardized scores for population norms.
Results
Of the 36 patients enrolled, 21 completed the study. At baseline, the mean (SD) patient age was 10.8 (5.2) years, and 61.1% were female. Disease progression modeling indicated no significant improvements in 4 of the 6 Vineland-3 subdomains analyzed over 24 months. Receptive Communication (+7.24; 95% CI 1.30–13.19; p = 0.02) and Coping Skills (+4.61; 95% CI 1.14–8.08; p = 0.01) subdomains showed significant improvements. However, for Receptive Communication, this improvement translated to a magnitude of only approximately 3 months in developmental progression over the 24-month period. BSID-III and WPPSI-IV subtests did not show any significant improvement.
Discussion
Despite a relatively small sample size and high withdrawal rate, BUTTERFLY data reveal a widening developmental gap between patients with DS and children with typical development over 24 months. These findings reinforce the critical need for disease-modifying therapies that address the underlying genetic cause of DS to improve long-term outcomes.
Details
- Title: Subtitle
- Natural History of Children and Adolescents With Dravet Syndrome: A 24-Month Follow-Up
- Creators
- Joseph Sullivan - University of California, San FranciscoElaine C Wirrell - Mayo Clinic in ArizonaKelly G Knupp - University of Colorado DenverMichael Ciliberto - University of IowaJulie Ziobro - University of MichiganDillon Y Chen - Yale UniversityJ Robert Flamini - Yale UniversityMuhammad Zafar - Chengdu Research Base of Giant Panda BreedingNicole LaVallee - Duke UniversityMiganush Stepanians - Duke UniversityPam Ventola - PROMETRA InternationalTanmay S Chavan - University of New HavenFei Wang - Linde (United States)Kimberly A Parkerson - Linde (United States)Barry Ticho - Linde (United States)
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.105(11), e214388
- DOI
- 10.1212/WNL.0000000000214388
- PMID
- 41237355
- PMCID
- PMC12622971
- NLM abbreviation
- Neurology
- ISSN
- 1526-632X
- eISSN
- 1526-632X
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- Stoke Therapeutics
Funding for the study and the development of this manuscript was provided by Stoke Therapeutics.
- Language
- English
- Date published
- 12/09/2025
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Neurology (Pediatrics)
- Record Identifier
- 9985027455902771
Metrics
12 Record Views