Clinical signatures of SYNGAP1-related disorders through data integration.
Publication/Presentation Date
3-19-2025
Abstract
PURPOSE: SYNGAP1 is a genetic neurodevelopmental disorder characterized by generalized epilepsy, autism, and intellectual disability. Despite a comparatively high prevalence, the longitudinal landscape remains relatively unexplored, and complete characterization is essential for clinical trial readiness.
METHODS: We combined electronic medical record data (n = 158) with insurance claims data (n = 246) to evaluate longitudinal progression of symptoms.
RESULTS: Phenotypes associated with SYNGAP1 included behavioral abnormalities (odds ratio [OR]: 12.35, 95% CI: 9.21-16.78), generalized-onset seizures (OR: 1.56, 95% CI: 1.20-2.02), autism (OR: 12.23, 95% CI: 9.29-16.24), and a developmental profile with prominent deficits in verbal skill acquisition. Several clinical features showed distinct age-related patterns, such as a more than 5-fold risk of autistic behavior emerging between 27 and 30 months. Generalized-onset seizures were significantly increased (OR: 4.05, 95% CI: 2.02-7.59) after 3 years of age and persisted over time. Valproic acid and clobazam were commonly used for epilepsy treatment, whereas risperidone, aripiprazole, and guanfacine were commonly used for behavior management. Valproate and lamotrigine were more effective at reducing seizure frequencies or maintaining seizure freedom than other antiseizure medications.
CONCLUSION: We delineated the seizure, developmental, and behavioral trajectories in SYNGAP1-related disorders, to improve diagnosis, prognosis, and clinical care, and facilitating clinical trial readiness.
Volume
27
Issue
6
First Page
101419
Last Page
101419
ISSN
1530-0366
Published In/Presented At
McKee, J. L., Magielski, J. H., Xian, J., Cohen, S., Toib, J., Harrison, A., Chen, C., Kim, D., Rathod, A., Brimble, E., Fitter, N., Graglia, J. M., Helde, K. A., McKeown Ruggiero, S., Boland, M. J., Prosser, B. L., Sederman, R., & Helbig, I. (2025). Clinical signatures of SYNGAP1-related disorders through data integration. Genetics in medicine : official journal of the American College of Medical Genetics, 27(6), 101419. Advance online publication. https://doi.org/10.1016/j.gim.2025.101419
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
40119723
Department(s)
Department of Pediatrics
Document Type
Article