Related Experiment Video
Updated: Sep 10, 2025

Author Spotlight: Generating Neuronal Phenotypic Profiles - A Protocol to Culture and Image Human Midbrain Dopaminergic Neurons
Published on: July 7, 2023
Characterizing Developmental and Behavioral Profiles in Developmental Synaptopathies to Inform Clinical Trial
Latha Valluripalli Soorya1, Camille W Brune1, Cristan A Farmer1
1Latha Valluripalli Soorya, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Camille W. Brune, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Cristan A. Farmer, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health; Edith V. Ocampo, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Natalie I. Berger, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Deborah A. Pearson, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston; Robyn M. Busch, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Department of Neurology and Epilepsy Center, Cleveland Clinic; Patricia Klaas, Center for General Neurology, Cleveland Clinic; Paige Siper, Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Kristn Currans, Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center; Amanda C. Gulsrud, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles; Jennifer M. Phillips, Department of Psychiatry and Behavioral Sciences, Stanford University, Rajna Filip-Dhima, Department of Neurology, Boston Children's Hospital, Harvard University; Sarah E. O'Kelley, Department of Psychology and Pediatrics, University of Alabama at Birmingham; Thomas W. Frazier, Department of Psychology, John Carroll University, Research Faculty, Departments of Pediatrics and Psychiatry at SUNY Upstate Medical University; Tess Levy, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai; Allison L. Wainer, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Joseph D. Buxbaum, Seaver Autism Center, Icahn School of Medicine at Mount Sinai; Craig M. Powell, Civitan International Research Center, University of Alabama at Birmingham; Jonathan A. Bernstein, Stanford University School of Medicine; Simon K. Warfield, Harvard University Medical School, and Department of Radiology, Boston Children's Hospital; Darcy A. Krueger, Cincinnati Children's Hospital Medical Center; E. Martina Bebin, University of Alabama at Birmingham; Hope Northrup, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Shafali S. Jeste, Keck School of Medicine, University of Southern California, and Children's Hospital Los Angeles; Alexander Kolevzon, Icahn School of Medicine at Mount Sinai; Elizabeth Berry-Kravis, Rush University Medical Center; Mustafa Sahin, Department of Neurology, Boston Children's Hospital, Harvard Medical School; Siddharth Srivastava, Boston Children's Hospital and Assistant Professor of Neurology, Harvard Medical School; Audrey Thurm, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health.
None:
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.
Related Concept Videos
Preclinical Development: Overview
Clinical Trials: Overview

