5 Clinical Trials for Williams Syndrome
The goal of this observational natural history study is to better characterize development, transition to adulthood, health and behavior of individuals diagnosed with Williams syndrome (WS) or carrying other variants of 7q11.23 chromosome and to build a DNA and tissue biobank with samples donated by affected individuals. The study has multiple arms focused on different aspects of WS. Participants with genetic diagnosis of WS or other variants of 7q11.23 and their family members are eligible to participate. Study participants may participate in one or multiple arms of the study: 1. Natural History Genotype-Phenotype Study to test the hypothesis that health, behavior, and developmental variability observed in WS is determined by genetic factors and to characterize those genetic changes. Participants of all ages are eligible to participate. Either a blood or saliva sample is required for participation. 2. Biobank: the research team is building a biobank enabling the development of new laboratory tools and models to study WS and test new treatment approaches. A blood sample is required for participation. Participants of all ages are eligible to participate. 3. Development arm of the study aims to delineate the development of language, cognition, personality, literacy and mathematics skills, and adaptive behavior from very early childhood through adulthood in individuals who have WS or Dup7. The purpose of this study also includes determining the predictors of specific aspects of development (e.g., word reading ability, language ability, spatial ability) for individuals with WS or Dup7. Affected individuals of all ages are eligible to participate. 4. Transition to Adulthood study aims to understand how young adults with WS make a successful transition out of high school into adulthood and to help them in this journey by providing a comprehensive psychosocial transition coupled with a medical transition plan. Individuals ages 14-25 years old are eligible to participate. Study requires three in person visits.
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: 1. 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. 2. 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.
Background: - Little is known about how the brain changes during childhood and adolescence, how genes affect this process, or how the brains of people with 7q11.23 genetic variation change during this period. Researchers are interested in using magnetic resonance imaging to study how the brain changes in healthy children and children with 7q11.23 genetic variation, including Williams syndrome and 7q11.23 duplication syndrome. Objectives: - To study developmental changes in the brains of healthy children and children who have been diagnosed with Williams syndrome,7q11.23 duplication syndrome, or other 7q11.23 genetic variation. Eligibility: * Healthy children and adolescents between 5 and 17 years of age. * Children and adolescents between 5 and 17 years of age who have been diagnosed with Williams syndrome, 7q11.23 duplication syndrome, or have other 7q11.23 genetic variation. Design: * Participants will have a brief physical examination and tests of memory, attention, concentration, and thinking. Parents will be asked about their child s personality, behavior characteristics, and social interaction and communication skills. * Both participants and their parents may be asked to complete additional questionnaires or take various tests as required for the study. * Participants will have approximately 10 hours of magnetic resonance imaging (MRI) scanning, usually over 4 to 5 days, within a one month period. Some of these tests will require the participants to do specific tasks while inside the MRI scanner. * Participants will be asked to return to the National Institutes of Health clinical center to repeat these procedures every 2 years thereafter until age 18.
Background: People with Williams Syndrome (WS) and supravalvular aortic stenosis (SVAS) have less elasticity in their blood vessels. This is called blood vessel stiffness. Blood vessels may have focal narrowings called stenoses or may just be globally more narrow. Objectives: Researchers want to see how blood vessel differences in people with Williams Syndrome and supravalvular aortic stenosis affect organs in the body including the heart, gut, kidneys, and brain. Eligibility: People ages 3-85 who have WS or SVAS Healthy volunteers ages 3-85 Design: * Participants will have yearly visits for up to 10 years. All participants will be offered the same tests. * Participants will give consent for the study team to review their medical records. If the participant is a child or an adult with WS, a parent or guardian will give the consent. * Participants will visit the NIH where they will have a physical exam and medical history. Based on their health history, participants will undergo a series of imaging tests and measures of blood vessel function over the course of 2-4 days. Tests of cognitive abilites will also be performed. Blood will be drawn and an IV may be placed for specific tests.
Purpose: Conduct a wait-list randomized controlled trial (RCT) of an inclusive physical activity program called PACE for adults with intellectual disability (ID) who are not yet showing signs of Alzheimer's Disease (AD)/age-related dementias (ARD). Participants: Participants include 120 adults with ID, their caregivers, and their coaches (up to 360 individual participants, grouped as triads), recruited through the University of North Carolina at Chapel Hill and the University of Arkansas. Participants also include 16 exercise professionals. Procedures (methods): Each cohort will include 20 triads who are randomly assigned to the PACE program or the waitlist control group.