Mapping the Phenotype in Adults With Phelan-McDermid Syndrome

• ClinicalTrials.gov Identifier: NCT03426059
• Recruitment Status: Completed
• First Posted: February 8, 2018
• Last Update Posted: April 2, 2021
• Sponsor: Boston Children's Hospital
• Collaborator: Phelan-McDermid Syndrome Foundation
• Information provided by (Responsible Party): Mustafa Sahin, Boston Children's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Phelan-McDermid Syndrome; Autism Spectrum Disorder; Intellectual Disability	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 Design

• Study Type: Observational
• Actual Enrollment: 24 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
• Actual Study Start Date: May 22, 2018
• Actual Primary Completion Date: December 31, 2019
• Actual Study Completion Date: December 31, 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Global cognitive ability [ Time Frame: Baseline ]
   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
2. Measure of Adaptive Behavior [ Time Frame: Baseline ]
   Using the standardized composite score from the Vineland Adaptive Behavior Scales (20-160, where higher values represent a better outcome) to measure adaptive behavior
3. Measure of Overall Language Abilities [ Time Frame: Baseline ]
   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
4. Measure of Overall Motor Functioning [ Time Frame: Baseline ]
   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
5. Measure of autism symptoms [ Time Frame: Baseline ]
   Using the standardized comparison score from the Autism Diagnostic Observation Scale (1-10, where higher values represent a worse outcome) to measure autism

Secondary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

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

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Maryland

National Institutes of Health

Bethesda, Maryland, United States, 20892

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, Texas

University of Texas Southwestern

Dallas, Texas, United States, 75390

Sponsors and Collaborators

Boston Children's Hospital

Phelan-McDermid Syndrome Foundation

Investigators

• Study Chair: Alexander Kolevzon, MD; Seaver Autism Center, Mount Sinai School of Medicine

More Information

• Responsible Party: Mustafa Sahin, Assistant in Neurology, Associate Professor of Neurology, Harvard Medical School, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT03426059
• Other Study ID Numbers: IRB-P00025776
• First Posted: February 8, 2018
• Last Update Posted: April 2, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mustafa Sahin, Boston Children's Hospital:

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

Additional relevant MeSH terms:

Intellectual Disability; Chromosome Disorders; Syndrome; Chromosome Deletion; Autism Spectrum Disorder; Disease; Pathologic Processes; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Monosomy; Aneuploidy; Chromosome Aberrations; Congenital Abnormalities; Genetic Diseases, Inborn