Authors :
Presenting Author: Andreas Brunklaus, MD – Royal Hospital for Children
M. Scott Perry, MD – Cook Children’s Medical Center; Ingrid Scheffer, AO, FAA, FAHMS – University of Melbourne, Austin Health; Joseph Sullivan, MD – University of California at San Francisco; Susana Boronat, MD, PhD – Hospital de la Santa Creu i Sant Pau; James Wheless, MD – Le Bonheur Children's Hospital; Linda Laux, MD – Ann & Robert H. Lurie Children's Hospital of Chicago; Anup Patel, MD – Nationwide Children’s Hospital; Colin Roberts, MD – Doernbecher Children’s Hospital; Dennis Dlugos, MD, MSCE – Children’s Hospital of Philadelphia; Deborah Holder, MD – Children's Hospital Los Angeles; Kelly Knupp, MD – Children’s Hospital Colorado; Matt Lallas, MD – Nicklaus Children’s Hospital; Steven Phillips, MD – Multicare Health System; Eric Segal, MD – Northeast Regional Epilepsy Group; Dennis Lal, PhD – Cleveland Clinic Lerner Research Institute; Elaine Wirrell, MD – Mayo Clinic; Sameer Zuberi, MD – Royal Hospital for Children; Lindsay Alfano, PT, DPT, PCS – Nationwide Children’s Hospital; Sarah Christensen, - – Encoded Therapeutics; Jacqueline Gofshteyn, MD – Encoded Therapeutics; Norman Huang, PhD – Encoded Therapeutics; Emma James, PhD – Encoded Therapeutics; Maria Candida Vila, PharmD, PhD – Encoded Therapeutics; Salvador Rico, MD, PhD – Encoded Therapeutics
Rationale:
Dravet syndrome (DS), a developmental and epileptic encephalopathy (DEE), is characterized by treatment-resistant seizures and global developmental delay including gait abnormalities, ataxia, and fine motor delays. ENVISION, an observational study, prospectively evaluated the course and impact of disease manifestations in young children living with SCN1A+ DS and families. Data collected during one and a half years of study will be presented.
Methods:
This is an international, multicenter, longitudinal, prospective study of children with SCN1A+ DS, aged six months to five years at study entry. Participants were assessed every three months to evaluate the longitudinal progression of motor function as evaluated using the Bayley Scales of Infant and Toddler Development (BSID-III), Neuromuscular Gross Motor Outcome measure, Motor Developmental Milestones (MDM), and Pediatric Evaluation of Disability Inventory (PEDI).
Results:
Across the overall cohort, all gross motor assessments showed continued gains with increasing age, albeit at a markedly slower rate than neurotypical children; however, individual trajectories were diverse. BSID-III normalized scores varied significantly; while many participants showed steady deviations from neurotypical peers in gross motor scores, some scored at the floor and others remained within the normative range. Mobility scores from the PEDI showed a critical threshold at age two years, when mobility gains slowed noticeably. This trend was mirrored in BSID-III gross motor skill measurements, with developmental quotient mean falling from 78% to 43% after age two years. Fine motor skills showed similar declines: despite subtle raw score gains (average of 2.3 points per year), participants increasingly deviated from their neurotypical peers over time. Among participants with more than two years at enrollment, significant declines in fine motor normalized scores were observed between each nominal visit, suggesting an early period of rapid decline prior to age two years.
Conclusions:
The ENVISION study reveals that children with DS demonstrate modest improvements in gross motor skills, although at a slower rate compared with neurotypical peers. While this developmental lag begins early in the disease course, it further intensifies after age two years. Fine motor skills show a rapid decline prior to age two, earlier than previously reported. These findings underscore the early onset of motor issues and the need for early therapeutic interventions that can address not only seizures but also the motor deficits that may have a significant impact on the lives of affected people with DS.
Funding: This study was funded by Encoded Therapeutics.