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Characterizing Developmental and Behavioral Profiles in Developmental Synaptopathies to Inform Clinical Trial Endpoints

Title: Characterizing Developmental and Behavioral Profiles in Developmental Synaptopathies to Inform Clinical Trial Endpoints
Language: English
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
Source: American Journal on Intellectual and Developmental Disabilities. 2025 130(5):414-437.
Availability: American Association on Intellectual and Developmental Disabilities. P.O. Box 1897, Lawrence, KS 66044-1897. Tel: 785-843-1235; Fax: 785-843-1274; e-mail: AJMR@allenpress.com; Web site: https://meridian.allenpress.com/aaidd
Peer Reviewed: Y
Page Count: 24
Publication Date: 2025
Document Type: Journal Articles; Reports - Research
Descriptors: Intellectual Disability; Genetic Disorders; Neurological Impairments; Measurement Techniques; Children; Adolescents; Young Adults; Severity (of Disability); Measures (Individuals); Behavior; Individual Development; Cognitive Processes
DOI: 10.1352/1944-7558-130.5.414
ISSN: 1944-7515; 1944-7558
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.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1482498
Database: ERIC