Mapping the Phenotype in Adults With Phelan-McDermid Syndrome

The protocol aims to comprehensively define the phenotype of Phelan-McDermid Syndrome and to identify potential genetic factors, which may play a role in the variability of the disease's outcomes. The first aim involves a physical exam, a neurological exam, collection of medical history information, a clinical genetic evaluation, blood work and neuropsychological assessments. If clinically indicated, the protocol collects information from medical tests. These medical tests may include electrocardiography, echocardiography, renal ultrasonography, and renal ultrasound.

Study Overview

• Status: Completed
• Conditions: Intellectual Disability; Autism Spectrum Disorder; Phelan-McDermid Syndrome
• Intervention / Treatment: Other: No Intervention

Detailed Description

Phelan-McDermid syndrome (PMS) or 22q13 Deletion syndrome, caused by a loss of one copy of the SHANK3 gene, is characterized by global developmental delay/intellectual disability, motor skills deficits, delayed or absent speech, and autism spectrum disorder. The goal of this study is to understand more about the PMS phenotypic outcomes and the biological pathways associated in the disorder, and to establish the foundation for future clinical trials in PMS and in other ID/ASD-associated disorders that share signaling pathways with PMS.

Individuals with PMS will be asked to participate in this study if they are 22 years of age or older with pathogenic deletions or mutations of the SHANK3 gene at time of enrollment. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. Parents and unaffected siblings may also be asked to consent to have blood drawn for analysis.

For this study, there is only one study visit. Study visit involves a physical exam, medical history questions, blood work and neuropsychological assessments. Individuals who have certain clinically indicated procedures (i.e. MRI, EEG, etc.) due will have them done as part of the research study

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

30 adult subjects with PMS will be enrolled across the 6 sites for this study

Description

Inclusion Criteria:

• Participant is 22 years of age and older at the time of enrollment
• Participant has been diagnosed with pathogenic deletions or mutations of the SHANK3 gene
• Participant is proficient in English
• Participant provided consent

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Phelan-McDermid Syndrome	Other: No Intervention; No Intervention. This is an observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global cognitive ability	Using standardized T-scores from the Mullen Scales for Early Learning (49 to 155, where higher values represent a better outcome) or full scale IQ scores from the Stanford Binet-5 (40 to 160, where higher values represent a better outcome) to measure global cognitive ability	Baseline
Measure of Adaptive Behavior	Using the standardized composite score from the Vineland Adaptive Behavior Scales (20-160, where higher values represent a better outcome) to measure adaptive behavior	Baseline
Measure of Overall Language Abilities	Using standardized T-scores from the Mullen Receptive Language and Expressive Language subscales (20 to 80, where higher values represent a better outcome), the standardized composite score Vineland Communication subscale (20-160, where higher values represent a better outcome) and the total raw scores from the Macarthur Bates Communication Developmental Inventory to measure overall language	Baseline
Measure of Overall Motor Functioning	Using standardized T-scores from the Mullen Gross and Fine Motor subscales (20-80, where higher values represent a better outcome) and the Vineland's Motor Skills Domain Standard Score (20-160, where higher values represent a better outcome) to assess motor ability	Baseline
Measure of autism symptoms	Using the standardized comparison score from the Autism Diagnostic Observation Scale (1-10, where higher values represent a worse outcome) to measure autism	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Receptive Language Abilities	Using standardized scores from the Peabody Picture Vocabulary Test (20-160, where higher values represent a better outcome) to measure receptive language abilities	Baseline
Measure of Expressive Language Abilities	Using standardized scores from the Expressive Vocabulary Test (20-160, where higher values represent a better outcome) to measure expressive language abilities	Baseline

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Phelan-McDermid Syndrome Foundation
• Investigators: Study Chair: Alexander Kolevzon, MD, Seaver Autism Center, Mount Sinai School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: ASD; Genotype; Autism Spectrum Disorder; Intellectual Disability; Phenotype; PMS; Mapping; Phelan-McDermid Syndrome; 22q13 Deletion Syndrome; SHANK3; ID
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Pathologic Processes; Genetic Diseases, Inborn; Disease; Neurobehavioral Manifestations; Congenital Abnormalities; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Chromosome Aberrations; Monosomy; Aneuploidy; Autism Spectrum Disorder; Syndrome; Intellectual Disability; Chromosome Disorders; Chromosome Deletion
• Other Study ID Numbers: IRB-P00025776

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No