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

NCT02461420 | Active Not Recruiting DMC

• 2 other identifiers: P000133001U54NS092090
• Study Type: observational
• Target: 205
• Locations: 1 country
• Sites: 5

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.

Conditions

Phelan-McDermid Syndrome; Autism Spectrum Disorder; Intellectual Disability

Keywords

Phelan-McDermid Syndrome; PMS; Genotype; Phenotype; Natural History; Mapping; 22q13 Deletion Syndrome; SHANK3; Autism Spectrum Disorder; ASD; Intellectual Disability; ID; EEG

Outcome Measures

Primary Outcomes (10)

• Change in global cognitive ability at 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

  Using Vineland Adaptive Behavior Scales to measure adaptive behavior

  12 months

• Change in language abilities at 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

  Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning

  12 months

• Change in autism symptoms at 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

  Using Mullen Scales for Early Learning or Stanford Binet-5 to measure global cognitive ability

  24 months

• Change in adaptive behavior at 24 months

  Using Vineland Adaptive Behavior Scales to measure adaptive behavior

  24 months

• Change is language abilities at 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

  Using composite of Mullen Subscales and Vineland Subscales to measure motor functioning

  24 months

• Change in autism symptoms at 24 months

  Using composite of Autism Diagnostic Observation Schedule and Repetitive Behavior Scales-Revised to measure autism

  24 months

Study Arms (1)

Phelan-McDermid Syndrome

Phelan-McDermid Syndrome

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institutes of Health (NIH): collaborator
• Office of Rare Diseases (ORD): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Phelan-McDermid Syndrome Foundation: collaborator

Study Sites (5)

Stanford University

Stanford, California, 94305, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (2)

• Bassell J, Srivastava S, Prohl AK, Scherrer B, Kapur K, Filip-Dhima R, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Buxbaum JD, Kolevzon A, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome. Pediatr Neurol. 2020 May;106:24-31. doi: 10.1016/j.pediatrneurol.2020.01.006. Epub 2020 Jan 31.

  PMID: 32107139 DERIVED

• Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M; Developmental Synaptopathies Consortium. Volumetric Analysis of the Basal Ganglia and Cerebellar Structures in Patients with Phelan-McDermid Syndrome. Pediatr Neurol. 2019 Jan;90:37-43. doi: 10.1016/j.pediatrneurol.2018.09.008. Epub 2018 Sep 21.

  PMID: 30396833 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood draw for future correlative studies in the PMS Biorepository of the Developmental Synaptopathies Consortium

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome; Autism Spectrum Disorder; Intellectual Disability

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Harvard Medical School

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: June 3, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

US (5)