Mapping the Phenotype in Adults With Phelan-McDermid Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Mapping the Phenotype in Adults With Phelan-McDermid Syndrome

Conditions
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Phelan-McDermid Syndrome, Autism Spectrum Disorder, Intellectual Disability

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phelan-McDermid Syndrome<br>Phelan-McDermid Syndrome | Other: No Intervention<br>* No Intervention. This is an observational study.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMS, ASD, Phelan-McDermid Syndrome, Genotype, Phenotype, Mapping, 22q13 Deletion Syndrome, SHANK3, Autism Spectrum Disorder, Intellectual Disability, ID