WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)

Williams Syndrome Skin and Vascular Elasticity Study (WS-SAVE Study)

Background:

Williams Syndrome (WS) is a genetic disorder. People with WS have less of a protein that allows parts of the body to stretch than other individuals. Researchers are interested in the stretchiness of the skin of people with WS and how it may relate to cardiovascular problems some people with WS develop. They are also interested in identifying exposures such as medications that may change the elasticity of the skin and vessels.

Objective:

To learn more about the skin and blood vessels in individuals with WS and how those tissues change over time.

Eligibility:

People ages 5-70 with WS.

People ages 1-70 with a medical condition that affects connective tissue.

Design:

Participants will be screened with a review of their medical records.

Participants will have 1 visit. Participants with WS may do so at a Williams Syndrome Association family meeting or camp, or at NIH. Other participants will be seen at NIH.

During the visit, participants will have height, weight, and blood pressure measured.

Researchers will listen to the participant s chest and abdomen.

Participants skin will be examined. It may be photographed.

Participants will have photos of their eyes and face taken.

Researchers will use a DermaLab Suction Cup Probe. A small suction cup will be placed on the arm with a sticker. It will pull lightly on the skin. This allows a computer to measure skin flexibility.

Researchers will use a SphygmoCor. A probe that looks like a dull pencil will be placed on the wrist, neck, and groin area. A computer will measure how fast the pulse is moving and will estimate blood vessel flexibility.

Participants may be invited to have these procedures repeated at a later date (2 years from now or more).

Study Overview

• Status: Completed
• Conditions: Hypertension; Cardiovascular Disease; Williams Syndrome; Multisystem Developmental Disorder; Elastin Gene Deletion

Detailed Description

Williams syndrome (WS) is a multisystem developmental disorder caused by deletion of 26-28 genes, including the elastin gene, located on chromosome 7q11.23. Cardiovascular disease in WS, including obstructive vascular disease and hypertension, and relatively mild skin changes are caused by the elastin gene deletion. Even though all WS subjects are missing one copy of this gene, the expression of cardiovascular problems is highly variable, ranging from no significant disease to severe generalized arteriopathy leading to infant death. The causes of vascular variability are currently unknown, and male gender is the only disease modifier described to date. Clinically, skin is described as abnormally soft, smooth and easily mobilized , while ultrastructurally the elastic fibers are abnormal with reduced amorphous elastin.

The overall objective of this study is to establish quantitative norms that can be used to determine the severity of vascular disease in elastin insufficiency and then to identify risk factors that contribute to that variability. It is also important to determine how stable/variable these findings are over time.

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

We will recruit three subject populations, individuals with WS and two control populations, one unaffected and one with known connective tissue disease. Affected subjects being screened for a research protocol or already on a research protocol at the NIH Clinical Center (CC) may be contacted by their physician about this study.@@@Subjects who are able to visit the NIH CC will be enrolled in person by the PI or approved AIs of the study, as mentioned in the previous section. For off-site subjects, the PI or approved AIs of this protocol may conduct an in-person, off-site meeting with the subject to carefully explain the research objectives, procedure(s), and relevant risks and discomforts of this protocol or attend WSA meetings that occur every 2 years and consent the subject at the meeting place.

Description

• INCLUSION/EXCLUSION CRITERIA:

For WS participants:

Individuals participating in this study must:

• Have a diagnosis of WS
• Be between the ages of 5 and 70 years old
• Be able to tolerate blood pressure measurements
• Have a parent/guardian available to provide consent and assist in answering medical questions.
• Express willingness to schedule an in-person assessment with us.

The only indication for study staff to terminate an individual s participation in this study would be if the family is unable to schedule an in-person assessment with us.

For unaffected control participants:

Individuals participating in this study must:

• Not have a diagnosis of WS or other connective tissue disease.
• Be between the ages of 1 and 70 years old
• If a minor, have a parent/guardian available to provide consent and assist in answering medical questions.

For control participants with connective tissue disease:

Individuals participating in this study must:

• Not have a diagnosis of WS
• Have a clinical or molecular diagnosis of connective tissue disease.
• Be between the ages of 1 and 70 years old
• If a minor, have a parent/guardian available to provide consent and assist in answering medical questions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Control participants with connective tissue disease; Not have a diagnosis of WS. Have a clinical or molecular diagnosis of connective tissue disease, between the ages of 1 and 70 years old
Unaffected Control participants; Not have a diagnosis of WS or other connective tissue disease, between the ages of 1 and 70 years old
WS participants; Have diagnosis of WS, between the ages of 5 and 70 years old. Be able to tolerate blood pressure measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify risk factors that contribute to the variability in cardiovascular and skin phenotype in individuals with Williams syndrome, primarily focusing on differences in elasticity and compliance	1) clinical and objective assessment of the vasculature and skin in individuals with WS, focusing on its elasticity; 2) analysis as to whether skin and vascular elasticity correlate with each other. 3) identification of genetic risk factors contributing to their variability, and 4) non-invasive measurement of urine biomarkers for oxidative stress. Note: with the NHLBI initial submission, items # 3 and 4 above will no longer be evaluated.	2-4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine how stable/variable these findings are over time	Skin and vascular elasticity analysis may be repeated in willing individuals at later dates (at least 2 years apart) to assess changes in the measurements with time.	2-4 years

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Manfred Boehm, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Urban Z, Peyrol S, Plauchu H, Zabot MT, Lebwohl M, Schilling K, Green M, Boyd CD, Csiszar K. Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype. Pediatr Dermatol. 2000 Jan-Feb;17(1):12-20. doi: 10.1046/j.1525-1470.2000.01703.x.
• Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010 Jan 21;362(3):239-52. doi: 10.1056/NEJMra0903074. No abstract available.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2017
• Primary Completion (Actual): December 15, 2017
• Study Completion (Actual): December 15, 2017

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: February 25, 2016
• First Posted (Estimated): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 13, 2026

More Information

Terms related to this study

• Keywords: Natural History; Cardiovascular Disease; CONNECTIVE TISSUE DISEASES; Elastin Gene Mutation; Multisystem Developmental Disorder
• Additional Relevant MeSH Terms: Aortic Valve Disease; Neurologic Manifestations; Nervous System Diseases; Vascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Heart Valve Diseases; Congenital Abnormalities; Intellectual Disability; Aortic Valve Stenosis; Chromosome Disorders; Aortic Stenosis, Supravalvular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Hypertension; Cardiovascular Diseases; Williams Syndrome; Connective Tissue Diseases
• Other Study ID Numbers: 160063; 16-H-0063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No