Williams Syndrome (WS) and Supravalvular Aortic Stenosis (SVAS) DNA and Tissue Bank

Study Overview
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Brief Summary
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Background: DNA tells the body how to grow and function. Williams-Beuren syndrome (WS) and Supravalvular Aortic Stenosis (SVAS) are rare diseases caused by changes in a part of a person s DNA. Symptoms of both conditions include vascular problems including narrow blood vessels and supravalvular aortic stenosis (SVAS) or supravalvular pulmonary stenosis. Individuals with WS may also have developmental challenges and personality differences. Researchers at the NIH want to find out why only some people with WS and SVAS have severe symptoms. They want to collect samples and data to see what DNA or environmental changes affect the severity of the disease. Objective: To identify the DNA differences or environmental changes that change the severity of WS and SVAS from person to person. Eligibility: People ages 0-85 with either WS, SVAS, and/or an SVAS-like condition Children and people with WS must have a parent or legal guardian to consent or help answer questions. Design: Participants will be screened with questions and medical history. Participants will have a 60-minute visit. They will provide blood or saliva samples. They or their parent/guardian will: Answer questions about how WS and SVAS affect them. Sign a form releasing their medical records for the study. If participant s regular doctor recommends surgery, researchers will ask the surgeon for skin or tissue samples that they might otherwise discard. These will be used to create stem cells to study in a lab. For up to 20 years, participants will have annual questionnaires by phone, email, or mail about their WS or SVAS. Participants may also be contacted if: They need to provide a new blood or saliva sample. Researchers need any other data. There is a follow-up study.

Detailed Description
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Our goal with the Williams syndrome (WS) and Supravalvular Aortic Stenosis (SVAS), deoxyribonucleic acid (DNA) and Tissue Bank is to collect enough samples from individuals with these rare conditions to ask questions about the genes that cause the many WS and SVAS related phenotypes, and to determine the genetic and environmental changes that modify the severity of disease from person to person. In addition, we would like to learn more about the natural history of these conditions and if there are environmental or genetic signatures that are associated with symptom presence. The protocol detailed here will provide for the collection of historical information, laboratory and imaging data, DNA and tissue to perform these studies now and in the future. Because technology changes rapidly and because this is a rare condition, our goal is to generate a collection that will be available for analysis for many years. In addition to DNA and tissue collection proposed, we would like to begin to use the specimens collected here to continue to ask questions about modifiers of vascular disease severity as well as effects on other organ systems in WS and SVAS.

Official Title
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Williams Syndrome (WS) and Supravalvular Aortic Stenosis (SVAS) DNA and Tissue Bank

Conditions
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Williams Syndrome, Supravalvular Aortic Stenosis, Cardiovascular Disease

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: We will recruit individuals with WS, SVAS or SVAS-like conditions and individuals with variation in WS genes other than elastin.. Children or adults participating in this study as part of the WS group must: be between the ages of 0 and 85 have a presumed or confirmed diagnosis of WS (typical or atypical deletions overlapping the WS region are acceptable as are clinical diagnoses made by a physician familiar with WS) have a parent/guardian available to provide consent and assist in answering medical questions Children or adults participating in the study as part of the SVAS group must: be between the ages of 0 and 85 have clinical features suggestive of SVAS or an SVAS-like condition OR have no clinical features of SVAS or an SVAS-like condition but have genetic testing results that imply affected status (SVAS has decreased penetrance). have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor (not applicable to adults) Children or adults with WS region gene changes (variation affecting one or more WS region genes): be between the ages of 0 and 85 have clinical or research genetic testing that reports gene variation in one or more genes in the WS region (ELN variants alone will be considered in the SVAS category but other changes to the region that include ELN plus other genes may be grouped in this category). have a parent/guardian available to provide consent and assist in answering medical questions if they are a minor or if they have cognitive impairment that would impede their ability to consent on their own behalf.

Ages Eligible for Study
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Maximum Age: 85 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 |
| --- | --- |
| SVAS group<br>Children or adults must: be between the ages of 0-85; have clinical features of SVAS; SVAS-like condition; have genetic testing results that imply affected status (SVAS has decreased penetrance) | |
| WS group<br>Children or adults must: be between the ages of 0 and 85; have a presumed or confirmed diagnosis of WS; have a parent/guardian available to provide consent and assist in answering medical questions | |
| WS region gene changes<br>Children or adults must: be between the ages of 0-85; have clinical or research genetic testing that reports gene variation in one or more genes in the WS region (ELN variants alone will be considered in the SVAS category but other changes to the region that include ELN plus other genes may be grouped in this category). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To collect historical information and bank specimens form individuals with Williams Syndrome and SVAS for future research | The overall objective of this study is to collect historical information and to bank DNA, cells and tissue from individuals with WS and SVAS to facilitate future research into the many phenotypes seen in these individuals. | ongoing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify genetic and environmental factors that contribute to the variability in different phenotypes in individuals with WS, SVAS, and SVAS-like conditions | To identify genetic and environmental factors that contribute to the variability in different phenotypes (vascular and non-vascular) in individuals with WS, SVAS and SVAS-like conditions. For the non-vascular features of WS and SVAS-like conditions for which a specific gene has not been implicated in the disease, we would also like to identify causative genes. | ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biospecimen Procurement, Laboratory Research Specimens, Sample Collection, Rare Diseases, Natural History