Longitudinal Data in a Cross-Disorder Caregiver-Entered Natural History Study of Genetic Neurodevelopmental Disorders
Abstract number :
3.131
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2025
Submission ID :
348
Source :
www.aesnet.org
Presentation date :
12/8/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Sarah Poliquin, PhD – COMBINEDBrain
Gracemarie Viggiano, BA – COMBINEDBrain
Sasha Elmizadeh, BA – COMBINEDBrain
Danielle Moberg, BA – COMBINEDBrain
Rithika Tummala, BA – COMBINEDBrain
Ananya Terala, BA – COMBINEDBrain
Katie Schmidt, BS – COMBINEDBrain
Nicholas Aguilar, BA – COMBINEDBrain
Corinne Hunnicutt, BA – COMBINEDBrain
Nikolas Bochorishvili, BA – COMBINEDBrain
William Keener, - – COMBINEDBrain
Martina Hannaalla, BA – COMBINEDBrain
Elijah Simon, BS – COMBINEDBrain
Taylor Morris, BS – COMBINEDBrain
Anna Pfalzer, PhD – COMBINEDBrain
Terry Jo Bichell, PhD, MPH – COMBINEDBrain
Rationale: Rare genetic neurodevelopmental disorders (NDDs) often involve complex, evolving phenotypes that challenge diagnosis, clinical management, and therapeutic development. Longitudinal natural history studies are essential for capturing the dynamic progression of these conditions, offering insights that cross-sectional data cannot provide.
Methods: Participants were recruited by patient advocacy groups that are members of COMBINEDBrain, in association with our plasma proteomics biomarker project. Participants enrolled in Matrix, a HIPAA- and GDPR-compliant data collection platform by Across Healthcare. Surveys completed include the GenomeConnect Health Survey (ClinGen), Vineland Adaptive Behavior Scales 3 - Caregiver Form, and the Pediatric Epilepsy Learning Healthcare System (PELHS) seizure survey.
Results: Since 2023, 861 patients or caregivers of patients with confirmed genetic NDDs/neurological disorders have enrolled in our study, representing 51 disorders across 29 countries, with 154 participants (17.9%) outside the US. So far, 98 participants from 27 disorders have provided longitudinal responses to the Genome Connect Health and Development initial survey, with follow-up responses an average of 14.5±2.03 (range 12-22) months after the first. 45 (46%) of participants reported at least one new symptom domain from the 19 symptom domains surveyed by the Health and Development questionnaire, with some users updating their responses to as many as 5 different domains. Of the 46% with changed responses, nearly 2 new domains (1.96±1.13) had become symptomatic. Participants with longitudinal responses range from 1 to 59 years of age, and age had no correlation with the number of new symptom domains (p = 0.233).
Conclusions: Cross-sectional data can miss details about the changing nature of genetic NDDs. Nearly half of our participants reported a new symptom in a previously-asymptomatic domain, between annual survey responses, and often reported 2 or more new domains. Interestingly, age was not correlated with the number of changes to symptomatic domains, showing that even adults with genetic NDDs continue to develop new symptoms. Detailed understanding of disease trajectories will be necessary for assessing treatment efficacy and cause of adverse events in clinical trials.
Funding: COMBINEDBrain
Translational Research