Characterizing Developmental and Behavioral Profiles in Developmental Synaptopathies to Inform Clinical Trial Endpoints
Year: 2025
Type: article
Study design: Observational Study
Abstract: The Developmental Synaptopathies Consortium is a multisite natural history network studying rare, neurogenetic syndromes associated with synaptic dysfunction and developmental delays. One aim of the Consortium is clinical trial readiness, including identifying clinical concepts and validating their measurement. We evaluated the scope and limitations of conventional cognitive and behavioral measurement strategies in 2-21-year-olds with Phelan-McDermid syndrome (PMS; N = 98), Tuberous Sclerosis Complex (TSC; N = 98), and PTEN Hamartoma Tumor syndrome (PHTS; N = 69). On average, intellectual disability (ID) severity was severe-to-profound in PMS, mild-to-moderate for TSC, and borderline (or absent) in PHTS. Severity of ID invalidated the use of many assessments, including standardized autism diagnostic measures. These results will inform trial planning for these and other similarly medically complex neurodevelopmental conditions.
Authors: Latha Valluripalli Soorya, Camille W. Brune, Cristan A. Farmer, Edith V. Ocampo, Natalie I. Berger, Deborah A. Pearson, Robyn M. Busch, Patricia Klaas, Paige Siper, Kristn Currans, Amanda C. Gulsrud, Jennifer M. Phillips, Rajna Filip-Dhima, Sarah E. O’Kelley, Thomas W. Frazier, Tess Levy, Allison L. Wainer, Joseph D. Buxbaum, Craig M. Powell, Jonathan A. Bernstein, Simon K. Warfield, Darcy A. Krueger, E. Martina Bebin, Hope Northrup, Shafali S. Jeste, Alexander Kolevzon, Elizabeth Berry-Kravis, Mustafa Sahin, Siddharth Srivastava, Audrey Thurm, on behalf of the Developmental Synaptopathies Consortium
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4413722821