Williams SyndromeNCT02706639
Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
An observational study of Williams Syndrome and Supravalvular Aortic Stenosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 3 sites in United States.
Trial summary
Williams syndrome is a rare genetic disorder occurring in 1:8000-12,000 individuals. It is caused by the deletion of 25-27 coding genes, including elastin (ELN) on the 7th human chromosome. Read more about this study
- Who is it for?
- Ages 1 day to 85 years
- Conditions the study is for
- Williams Syndrome, Supravalvular Aortic Stenosis, Cardiovascular Disease
- How many people
- 305 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 May 2016to 7 Mar 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Affected: 1) people with WS (adults and children), 2) people with ELN-related SVAS (adults and children), 3) people with SVAS-like conditions (those with an SVAS phenotype but no known pathologic variant in ELN, (adults and children)) 4) individuals with single or oligogenic variation in WS genes other than ELN (adults and children) Unaffected: 5) unaffected family members of participating subjects (children or adults), enrolled as controls 6) unrelated unaffected adult controls.
Who may be able to join
- We will recruit individuals with WS, SVAS or SVAS-like conditions, individuals with variation in WS genes other than ELN and unaffected family members or unrelated controls
- 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/SVAS-like group must:
- be between the ages of 0 and 85
Show all 18Show fewer
- have clinical features suggestive of SVAS or an SVAS-like condition OR have no clinical features of SVAS or of 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.
- Children or adults serving as unaffected family members or adult unrelated controls must:
- family members be between the ages of one month old and 85 years old
- unrelated controls be between the ages 18 and 85 years old
- not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant.
- In some cases, an individual may appear to be unaffected, but upon genetic testing may be found to be an asymptomatic carrier for gene variant. If that happens, they will be transferred to the appropriate affected research group.
- The eligible age range for unaffected family members participating in this study includes all family members from one month onwards. This inclusive approach is undertaken to comprehensively grasp the affected status across all family members, avoiding any form of age-based discrimination. Understanding that certain cases may not exhibit phenotypic indications of affected status at a young age, it becomes crucial to gather early health characteristics of individuals who may initially appear unaffected but later manifest disease findings. Participation in research, as previously noted, has a potential to identify people at risk who were previously thought to be healthy.
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Nationwide Children's Hospital
Columbus, Ohio, 43205
Washington University School of Medicine
St Louis, Missouri, 63110-1010
About this study
Williams syndrome is a rare genetic disorder occurring in 1:8000-12,000 individuals. It is caused by the deletion of 25-27 coding genes, including elastin (ELN) on the 7th human chromosome. Haploinsufficiency for these genes leads to the features of the condition, including:
- Distinctive facial features;
- Characteristic vascular problems including hypertension, focal vascular stenosis, (when present in the aorta this is referred to as SVAS), vascular stiffness and differences in heart rate variability;
- Endocrine abnormalities including hypercalcemia, hypothyroidism, and early puberty;
- Metabolic concerns with colic and failure to gain weight in infancy and obesity and early glucose intolerance in adulthood;
- Characteristic neurocognitive profile comprised of cognitive impairment, high sociality with concurrent social awkwardness, difficulty with visual-spatial tasks, relative strengths in speech, and lack of social fear;
- Anxiety and chronic pain in adulthood
Read more
Most individuals with WS carry the same basic deletion on Chromosome 7q11.23. However, each feature may present as mild or more severe in any given individual. Variation in the presence and severity of these vascular phenotypes remains unexplained.
The supravalvar aortic stenosis (SVAS) phenotype is caused by haploinsufficiency for elastin. This can come about due to the WS deletion (as above) or due to heterozygous variation in elastin (ELN) gene itself in this region. When this protein is reduced, connective tissues lose its strength, flexibility, and overall support. When this happens in the aorta, it may cause vascular narrowing that presents as shortness of breath, chest pain, and even heart failure if left untreated. Narrowing also occurs in other vessels especially the pulmonary and renal arteries. Changes in non-vascular elastic tissues such as the skin and lungs also occur. As in WBS, phenotypic variation also occurs in people with ELN gene changes--This variability remains unexplained despite all the on-going research.
Most individuals with features of SVAS have either WS or an elastin variant. There are, however, a smaller number of individuals with the phenotypic features of the condition whose genetic underpinnings are yet to be defined (they are referred to as SVAS-like).
Additionally, there are 26 other coding genes within the WS critical region that contribute to various other features of the condition
Objective:
- To collect historical information and to bank DNA, cells, and tissue from individuals with genetic alterations in the WS/ELN gene region, those with an SVAS -like phenotype and unaffected family members/controls to facilitate future research into the many phenotypes seen in these individuals.
- Currently, we plan to use the collected samples 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, individuals with variation in WS genes other than elastin and unaffected family members and controls. 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 as well as modifiers. Likewise, by evaluating people with variation in other WS region genes, we can determine what contribution those genes make to the studied phenotypes. Controls will be both used to assess the frequency of genetic features in people without the phenotype in question and to evaluate heritability, penetrance, and expressivity of relevant variants.
Eligibility:
People ages 0-85 with either WS, SVAS, and/or an SVAS-like condition, unaffected family members or adult unrelated controls.
Design:
This study is not a treatment protocol.
This study will consist of:
Collection of personal history (questionnaires) and medical record data (relevant physician notes, lab and diagnostic tests and studies) to study the natural history of these conditions, allow stratification of disease severity, and identification of environmental risk factors;
Collection of blood, saliva, urine and surgical tissue waste to allow DNA and RNA preparation as well as study of tissues both in situ and through the generation of IPSCs;
Expression studies on available tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues) to look for differential regulation of target genes;
Direct imaging of tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues);
Storage of collected data and specimens for future research;
A questionnaire may be sent to participants or parent/guardian or LAR to respond on behalf of participant.
Read the detailed description
Our goal with the Williams syndrome (WS) and Supravalvar 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 genetic changes within and outside of the WS critical region that influence disease outcomes, including primary disease drivers and modifiers of disease severity. Our primary focus is on drivers of vascular disease in WS, WS-region variation, SVAS and SVAS-like conditions, but investigation of genetic and environmental factors that influence other systems is also anticipated.
- Keywords
- Biospecimen Procurement, Laboratory Research Specimens, Sample Collection, Rare Diseases, Natural History
- Medical subject headings
- Williams Syndrome, Aortic Stenosis, Supravalvular, Cardiovascular Diseases, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SVAS/SVAS-like group | 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) | |
| Unaffected related (family member) controls | Children or adults: family members be between the ages of one month old and 85 years old, not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant. | |
| Unaffected unrelated controls | Adults, 18-85: unrelated controls be between the ages 18 and 85 years old, not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant. | |
| WS group | 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 | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ongoing
Secondary outcomes (1)
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.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study start11 May 2016
- Primary completion7 Mar 2025
- Study completion7 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Williams SyndromeStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 305 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Manfred Boehm, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02706639
- Sponsor's protocol ID
- 160074
- Other IDs
- 16-H-0074
- Status last verified
- 7 Aug 2026
- First submitted
- 8 Mar 2016
- Last updated
- 28 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known.
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
- ClinicalTrials.gov ID
- NCT02706639
- Acronym / sponsor ID
- 160074
- Keywords
- Biospecimen Procurement, Laboratory Research Specimens, Sample Collection, Rare Diseases, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 11 May 2016 (actual)
- Primary completion
- 7 Mar 2025 (actual)
- Study completion
- 7 Mar 2025 (actual)
- First posted
- 11 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Williams syndrome is a rare genetic disorder occurring in 1:8000-12,000 individuals. It is caused by the deletion of 25-27 coding genes, including elastin (ELN) on the 7th human chromosome. Haploinsufficiency for these genes leads to the features of the condition, including:
- Distinctive facial features;
- Characteristic vascular problems including hypertension, focal vascular stenosis, (when present in the aorta this is referred to as SVAS), vascular stiffness and differences in heart rate variability;
- Endocrine abnormalities including hypercalcemia, hypothyroidism, and early puberty;
- Metabolic concerns with colic and failure to gain weight in infancy and obesity and early glucose intolerance in adulthood;
- Characteristic neurocognitive profile comprised of cognitive impairment, high sociality with concurrent social awkwardness, difficulty with visual-spatial tasks, relative strengths in speech, and lack of social fear;
- Anxiety and chronic pain in adulthood
Most individuals with WS carry the same basic deletion on Chromosome 7q11.23. However, each feature may present as mild or more severe in any given individual. Variation in the presence and severity of these vascular phenotypes remains unexplained.
The supravalvar aortic stenosis (SVAS) phenotype is caused by haploinsufficiency for elastin. This can come about due to the WS deletion (as above) or due to heterozygous variation in elastin (ELN) gene itself in this region. When this protein is reduced, connective tissues lose its strength, flexibility, and overall support. When this happens in the aorta, it may cause vascular narrowing that presents as shortness of breath, chest pain, and even heart failure if left untreated. Narrowing also occurs in other vessels especially the pulmonary and renal arteries. Changes in non-vascular elastic tissues such as the skin and lungs also occur. As in WBS, phenotypic variation also occurs in people with ELN gene changes--This variability remains unexplained despite all the on-going research.
Most individuals with features of SVAS have either WS or an elastin variant. There are, however, a smaller number of individuals with the phenotypic features of the condition whose genetic underpinnings are yet to be defined (they are referred to as SVAS-like).
Additionally, there are 26 other coding genes within the WS critical region that contribute to various other features of the condition
Objective:
- To collect historical information and to bank DNA, cells, and tissue from individuals with genetic alterations in the WS/ELN gene region, those with an SVAS -like phenotype and unaffected family members/controls to facilitate future research into the many phenotypes seen in these individuals.
- Currently, we plan to use the collected samples 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, individuals with variation in WS genes other than elastin and unaffected family members and controls. 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 as well as modifiers. Likewise, by evaluating people with variation in other WS region genes, we can determine what contribution those genes make to the studied phenotypes. Controls will be both used to assess the frequency of genetic features in people without the phenotype in question and to evaluate heritability, penetrance, and expressivity of relevant variants.
Eligibility:
People ages 0-85 with either WS, SVAS, and/or an SVAS-like condition, unaffected family members or adult unrelated controls.
Design:
This study is not a treatment protocol.
This study will consist of:
Collection of personal history (questionnaires) and medical record data (relevant physician notes, lab and diagnostic tests and studies) to study the natural history of these conditions, allow stratification of disease severity, and identification of environmental risk factors;
Collection of blood, saliva, urine and surgical tissue waste to allow DNA and RNA preparation as well as study of tissues both in situ and through the generation of IPSCs;
Expression studies on available tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues) to look for differential regulation of target genes;
Direct imaging of tissues (lymphocytes, IPSCs, vascular, skin, other collected tissues);
Storage of collected data and specimens for future research;
A questionnaire may be sent to participants or parent/guardian or LAR to respond on behalf of participant.
Detailed description
Our goal with the Williams syndrome (WS) and Supravalvar 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 genetic changes within and outside of the WS critical region that influence disease outcomes, including primary disease drivers and modifiers of disease severity. Our primary focus is on drivers of vascular disease in WS, WS-region variation, SVAS and SVAS-like conditions, but investigation of genetic and environmental factors that influence other systems is also anticipated.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| SVAS/SVAS-like group | – | –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) |
| Unaffected related (family member) controls | – | –Children or adults: family members be between the ages of one month old and 85 years old, not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant. |
| Unaffected unrelated controls | – | –Adults, 18-85: unrelated controls be between the ages 18 and 85 years old, not carry a diagnosis of WS, SVAS, an SVAS-like condition or a known (at the time of enrollment) WS gene region variant. |
| WS group | – | –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 | – | –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). |
Who may qualify
- Ages
- 1 day to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Affected: 1) people with WS (adults and children), 2) people with ELN-related SVAS (adults and children), 3) people with SVAS-like conditions (those with an SVAS phenotype but no known pathologic variant in ELN, (adults and children)) 4) individuals with single or oligogenic variation in WS genes other than ELN (adults and children) Unaffected: 5) unaffected family members of participating subjects (children or adults), enrolled as controls 6) unrelated unaffected adult controls.
Key inclusion criteria (18 listed)
- We will recruit individuals with WS, SVAS or SVAS-like conditions, individuals with variation in WS genes other than ELN and unaffected family members or unrelated controls
- 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
- 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 of an SVAS-like condition but have genetic testing results that imply affected status (SVAS has decreased penetrance).
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To collect historical information and bank specimens form individuals with Williams Syndrome and SVAS for future research
Time frame: ongoing
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.
1 secondary outcome
To identify genetic and environmental factors that contribute to the variability in different phenotypes in individuals with WS, SVAS, and SVAS-like conditions
Time frame: ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is not yet known.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manfred Boehm, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Williams Syndrome and Supravalvular Aortic Stenosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To collect historical information and bank specimens form individuals with Williams Syndrome and SVAS for future research (time frame: ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.