Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome

September 23, 2022 updated by: Mustafa Sahin, Boston Children's Hospital
The purpose of this study is to comprehensively characterize PMS using standardized medical, cognitive, and behavioral measures and to track the natural history of the syndrome using repeated longitudinal assessments. In addition, this study will be aiming to identify biomarkers using neuroimaging, including diffusion tensor imaging and identify genetic factors which contribute to diverse phenotypes in patients with PMS.

Study Overview

Status

Recruiting

Conditions

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 phenotype and the biological pathways associated with ID and ASD 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 18 months or older with pathogenic deletions or mutations of the SHANK3 gene at time of enrollment, as well as healthy controls. 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.

The study involves 3 on site visits over 2 years. Study visits involve a physical exam, medical history questions, blood work and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Study Type

Observational

Enrollment (Anticipated)

190

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Principal Investigator:
          • Jon Bernstein, MD, PHD
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Principal Investigator:
          • Elizabeth Berry-Kravis, MD, PhD
        • Principal Investigator:
          • Latha Soorya, PhD
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health
        • Contact:
        • Principal Investigator:
          • Audrey Thurm, PhD
    • Massachusetts
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Alexander Kolevzon, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

  • Individuals older than 18 months of age with pathogenic deletions or mutations of the SHANK3 gene
  • English speaking individuals

Exclusion Criteria:

  • Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
  • For subjects involved in imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator
  • For subjects involved in EEG/ ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or over age 11 at the time of enrollment.
  • Unwilling or unable to comply with study procedures and assessments

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Phelan-McDermid Syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in global cognitive ability at 12 months
Time Frame: 12 months
Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability
12 months
Change in adaptive behavior at 12 months
Time Frame: 12 months
Using Vineland Adaptive Behavior Scales to measure adaptive behavior
12 months
Change in language abilities at 12 months
Time Frame: 12 months
Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language
12 months
Change in motor functioning at 12 months
Time Frame: 12 months
Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning
12 months
Change in autism symptoms at 12 months
Time Frame: 12 months
Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism
12 months
Change in global cognitive ability at 24 months
Time Frame: 24 months
Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability
24 months
Change in adaptive behavior at 24 months
Time Frame: 24 months
Using Vineland Adaptive Behavior Scales to measure adaptive behavior
24 months
Change is language abilities at 24 months
Time Frame: 24 months
Using composite of Mullen Subscales, Vineland Subscales and Macarthur Bates Communication Developmental Inventory to measure language
24 months
Change in motor functioning at 24 months
Time Frame: 24 months
Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning
24 months
Change in autism symptoms at 24 months
Time Frame: 24 months
Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
Office of Rare Diseases (ORD)
Phelan-McDermid Syndrome Foundation

Investigators

  • Study Chair: Alexander Kolevzon, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

May 11, 2015

First Submitted That Met QC Criteria

June 1, 2015

First Posted (Estimate)

June 3, 2015

Study Record Updates

Last Update Posted (Actual)

September 26, 2022

Last Update Submitted That Met QC Criteria

September 23, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P00013300
  • 1U54NS092090 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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