Williams Syndrome

What Causes Williams Syndrome?

Williams syndrome is caused by a defect in a chromosome, one of the 46 structures inside cells that carry genetic material. In WS, a specific part of chromosome 7 is missing. This section of the chromosome contains more than 25 genes, collections of DNA that control the development and function of cells in the body. The loss of genes from this area of chromosome 7 causes the symptoms of WS.

Scientists do not fully understand how many of the specific missing genes account for WS symptoms. For example, the ELN gene seems to be associated with joint and heart abnormalities, and the GTF2IRD1 may be responsible for the disorder’s distinctive facial features. Studies have linked several of the genes to the syndrome’s cognitive symptoms, but it’s not clear precisely how the genes are associated with the neurological effects.

Is Williams Syndrome Hereditary?

Most cases of Williams syndrome are not inherited. In rare cases, WS has been observed to run in families, but most of the time, a person with WS has no family history of the syndrome. Although the disorder has a genetic origin, the abnormal change to chromosome 7 usually happens randomly during sperm or egg cell development. Therefore, the parents do not carry the damaged chromosome and do not pass it directly to the child.

When WS is inherited, it is via the autosomal dominant pattern. This means that a child will develop the disorder if they inherit only one copy of the altered chromosome from either parent.

How Is Williams Syndrome Detected?

WS is usually diagnosed in infancy or early childhood as symptoms begin to emerge. Early signs of WS may include:

• Feeding difficulties
• Delays in motor development milestones such as sitting or walking
• Problems with coordination
• Low muscle tone or unusually mobile joints
• Slow growth
• Distinctive facial features
• Intellectual impairment
• Visual-spatial impairments, along with language and memory strengths
• Sleep difficulties
• Vision problems
• Chronic ear infections
• Heart problems
• Elevated calcium levels or other endocrine abnormalities
• Over-friendliness
• Anxiety

How Is Williams Syndrome Diagnosed?

A doctor may suspect WS if a child shows symptoms typical of the disease. The diagnostic process will usually include an evaluation of the patient’s medical history, along with physical, cognitive, and neurological exams. The doctor may refer the patient to a geneticist for further diagnostic testing. Diagnostic steps may consist of:

• Blood tests to look for elevated calcium levels
• Electrocardiogram (EKG) to look for heart abnormalities
• Genetic testing to look for the characteristic deletion in chromosome 7

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Williams Syndrome Treated?

There is no cure for Williams syndrome. Treatments and therapies are aimed at individual symptoms, which vary from case to case. Potential treatment options include:

• Feeding assistance
• Special education
• Counseling for behavioral issues
• Medications to treat anxiety or attention deficit
• Monitoring for heart conditions (surgery may be necessary in some cases)
• Medications or nutritional assistance to treat elevated calcium levels
• Hormone therapy to treat early puberty

How Does Williams Syndrome Progress?

The long-term outlook for people with Williams syndrome varies depending on the severity and type of symptoms. People with mild intellectual disabilities may be able to live independently, although most will require the help of a caregiver. Early treatment, therapeutic programs, and life-skills education can increase the likelihood that a person with the syndrome will eventually live independently.

Some of Williams syndrome’s complications, such as heart problems, can be life-threatening, and people with severe medical issues may have a shortened life expectancy.

How Is Williams Syndrome Prevented?

There is no known way to prevent WS. However, people with a family history of the disorder should consider consulting a genetic counselor before having children.

Williams Syndrome Caregiver Tips

Most people with Williams syndrome also suffer from other brain disorders or mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with WS:

• It is common for people with WS to have problems with attention and other symptoms of attention-deficit/hyperactivity disorder (ADHD).
• Some people with Williams syndrome also have obsessive-compulsive disorder (OCD) symptoms at some point in their lives.
• Many people with WS suffer from anxiety disorders, particularly phobias and generalized anxiety disorder (GAD).
• Williams syndrome and autism share some features, but how or if the two disorders may be related is unclear.

Williams Syndrome Brain Science

People with Williams syndrome often have impaired skills in the areas of visual and spatial understanding while, at the same time, having average or above-normal skills in spoken language. This discrepancy in cognitive abilities has led scientists to speculate that the syndrome’s genetic cause somehow targets one cognitive area (visual-spatial cognition) while leaving another (language) untouched. However, recent research has suggested that the syndrome’s effect on cognition may be more complex than that.

One study found that although people with WS had distinct spatial impairments, they had some areas of relative strength in the spatial realm. On the other hand, they showed some isolated language deficiencies despite an overall strong facility with language. The researchers suggest that these results may indicate that WS causes a broad problem with cognitive development that manifests in different ways in the spatial and language areas.

Williams Syndrome Research

Title: Williams Syndrome Strength, Hormones, Activity & Adiposity, DNA Programming, Eating Study (SHAAPE)

Stage: Recruiting

Principal investigator: Barbara Pober, MD

Massachusetts General Hospital

Boston, MA 

Williams syndrome (WS) is a rare microdeletion genetic disorder with a broad phenotype including many endocrine and metabolic abnormalities. Dr. Pober and colleagues at MGH have reported the following findings in adults with WS: abnormal body composition (excess body fat accumulation with a lipedema phenotype), decreased bone mineral density, abnormal glucose tolerance, and reduced lean mass. Despite the high prevalence and potential effect of metabolic abnormalities on the health of persons with WS, their full phenotypic range, potential causal factors (either genetic and/or hormonal) along with their impact on other aspects of health (such as the risk of falls and fractures or interaction with emotional behavioral concerns) remain incompletely characterized. The purpose of the current study in a large cohort of subjects with WS is to: collect further information to characterize the timing of onset and distribution of body fat; better characterize the hormonal status of WS subjects; and screen for genetic variation using single-nucleotide-polymorphism (SNP) analysis that could elucidate genetic contributors to the lipedema phenotype as well as the other observed metabolic and bone abnormalities.

Title: Buspirone Treatment of Anxiety in Williams Syndrome

Stage: Recruiting

Principal investigator: Robyn P. Thom, MD

Massachusetts General Hospital

Boston, MA 

The purpose of this study is to do a preliminary assessment of whether buspirone is effective, safe, and tolerable in the treatment of anxiety in children, adolescents, and adults with Williams syndrome.

After being informed about the study and potential risks, all patients or legal guardians giving written informed consent will be screened for study eligibility. Patients who meet the eligibility requirements will participate in a 16-week, flexibly-dosed, open-label trial of buspirone. The dose of buspirone will be adjusted over the first 12 weeks of the study, and a stable dose will be maintained for the final four weeks of the trial. Adverse effects will be reviewed at each visit, and standardized measures of anxiety will be conducted at weeks 4, 8, 12, and 16.

Title: Defining the Brain Phenotype of Children With Williams Syndrome

Stage: Recruiting

Principal investigator: Karen F Berman, MD

National Institute of Mental Health

Bethesda, MD 

Little is known about how the brain changes during childhood and adolescence, how genes affect this process, or how the brains of people with Williams syndrome change during this period. Genetic features of Williams syndrome affect the brain s development, but the details of this process have not been studied over time. Researchers are interested in using magnetic resonance imaging to study how the brain changes in healthy children and children with Williams syndrome and related genetic disorders.

Objectives: To study developmental changes in the brains of healthy children and children who have been diagnosed with Williams syndrome or a related genetic disorder.

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 or genetic characteristics that overlap with Williams syndrome.

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, 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 two years thereafter until age 18.