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

Active, not recruiting

• Conditions: Phelan-McDermid Syndrome; Autism Spectrum Disorder; Intellectual Disability

• Registration Number: NCT02461420
• Lead Sponsor: Boston Children's Hospital

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-11
• Study First Submitted QC: 2015-06-01
• Study First Posted: 2015-06-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 205

Inclusion Criteria

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Trial Locations

Locations (5)

Stanford University; 🇺🇸 Stanford, California, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

National Institutes of Health; 🇺🇸 Bethesda, Maryland, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States