Williams syndrome

Williams syndrome is caused by a missing piece (deletion) of genetic material from a specific region of chromosome 7. The deleted region includes more than 25 genes.

CLIP2 , ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that the loss of the ELN gene is associated with the connective tissue abnormalities and heart disease in many people with this condition. Studies suggest that deletions of CLIP2 , GTF2I , GTF2IRD1 , LIMK1 , and perhaps other genes, may help explain many of the unique behavioral characteristics and cognitive difficulties. Loss of the GTF2IRD1 gene may also contribute to the distinctive facial features often present. The relationship between some of the other deleted genes and the features of Williams syndrome is not yet known.

The diagnosis of Williams syndrome (WS) is established by genetic testing identifying a specific microdeletion at chromosome 7q11.23 (on the long arm of chromosome 7, at a position designated 11.23).

Because the symptoms and severity of WS vary, no single feature is needed to establish the diagnosis. WS may first be suspected in individuals with:

• Cardiovascular (heart) disease (elastin arteriopathy) - any artery may be narrowed. Supravalvar aortic stenosis (SVAS) is the most common heart abnormality, occurring in 75% of people with WS. Peripheral pulmonic stenosis is common in infancy.
• Distinctive facial features - broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. In older children and adults, the face appears longer and more gaunt.
• Connective tissue abnormalities causing a hoarse voice, inguinal or umbilical hernia, bowel or bladder diverticulum, rectal prolapse, joint limitation or laxity, and soft, lax skin.
• Intellectual disability - some degree is present in most people with WS. Some have average intelligence.
• Strengths in verbal short-term memory and language, and extreme weakness in visuospatial construction.
• Unique personality - overfriendliness, empathy, generalized anxiety, specific phobias, and attention deficit disorder are commonly present.
• Growth abnormalities - prenatal growth deficiency, failure to thrive in infancy, poor weight gain and growth in the first four years, and a brief pubertal growth spurt.
• Endocrine abnormalities such as hypercalcemia, high calcium urine levels (hypercalciuria), hypothyroidism, and early puberty.

Most cases of Williams syndrome are not inherited. The condition typically occurs due to random events during the formation egg or sperm cells in a parent. Therefore, it most often occurs in people with no family history of Williams syndrome.

In a small portion of cases, people with Williams syndrome inherit the chromosome deletion from a parent with the condition. In these cases, it is inherited in an autosomal dominant manner. This is because having only one changed copy of chromosome 7 in each cell is enough to cause signs and symptoms.

Regardless of whether Williams syndrome occurs randomly or is inherited from a parent, each child of a person with Williams syndrome has a 50% chance of inheriting the condition.

We searched PubMed, the database of published medical literature, as well as medical websites and the websites of support and advocacy groups for a connection between intraductal papillomas and Williams syndrome. However, we were not able to find any study, case report or resource suggesting women with Williams syndrome were at an increased risk for intraductal papillomas.

This however does not mean there is not a connection, only that such a connection has not been published. We will provide resources below for you to explore your question further.

We strongly recommend that you seek the advice of a genetics professional for further information regarding your specific risks to have a child affected by Williams syndrome. We encourage you to visit the Living With section for guidance on how to locate a genetics professional in your area.

General information regarding the inheritance of Williams syndrome is provided below. The risk posed to the siblings of an individual with Williams syndrome (proband) depends on the status of the proband's parents. If a proband's parent is affected, the risk is 50% to all siblings. If neither parent is clinically affected, the risk to the siblings of a proband appears to be low because few familial cases have been reported. The clinically unaffected sibling of an individual with Williams syndrome who has clinically unaffected parents likely has no greater risk to have a child with Williams syndrome than does the average person.

There is no known way to prevent the genetic problem that causes Williams syndrome. Prenatal testing is available for couples with a family history of Williams syndrome who wish to conceive. For instance, for pregnancies at 50% risk of Williams syndrome, fluorescence in situ hybridization, or FISH testing, may be used to detect the microdeletion of the WBSCR critical region in fetal cells obtained by chorionic villus sampling (CVS) at about 10-12 weeks' gestation or amniocentesis usually performed at about 15-18 weeks' gestation. Prenatal testing may also be offered to unaffected parents who have had a child with Williams syndrome (and perhaps other family members) because of the recurrence risk associated with the possibility of germline mosaicism or inversion polymorphism or in cases of parental anxiety. Prenatal testing for pregnancies not known to be at increased risk for Williams syndrome is available, but is rarely used because most cases are a single occurrence in a family.

Nonprofit support and advocacy groups can offer a way to connect to others who may have similar experiences. Information gathered from affected members of these groups has sometimes changed the direction of research by bringing to light commonalities that were missed because few physicians actually saw many affected people with the condition or did not ask the right questions to make the discovery. In addition, members of the Medical Advisory Boards may be aware of unpublished information and private ongoing research or may become interested in pursuing a research interest brought to their attention by the affected members of a group. The Information Center provides the names of organizations and researchers for informational purposes only and not as an endorsement of services.

The Williams Syndrome Foundation has a very active group for adults with Williams syndrome and their families. They also have a registry where they collect information about people with Williams syndrome so more can be known. Their website has information about medical issues and research as well as ways to connect to other families. On the Williams Syndrome Association website, Dr. Barbara Pober is listed as a medical researcher who is very interested in the medical issues faced by those with Williams syndrome as they age.

Williams Syndrome Association
570 Kirts Blvd
Suite 223
Troy, MI 48084-4156
Toll-free: 800-806-1871
Telephone: 248-244-2229
Fax: 248-244-2230
E-mail: info@williams-syndrome.org
Website: http://www.williams-syndrome.org

In addition to kidney and heart problems, some of the medical issues which may develop as people with Williams syndrome age include:

• Hearing loss (including build up of wax)
• Hypercalemia
• Hypothyroidism
• Diabetes
• Weight gain (about 50% remain thin however)
• Dental problems (need help at home with dental care)
• Gastrointestinal problems
  • Abdominal pain
  • Constipation
  • Diverticulitis
• Anxiety disorders
• Possible accelerated aging (premature graying of hair)
• Possible accelerated cognitive decline
• For more details see: Adult Medical Issues

Please note that people with Williams syndrome may also have difficulties with anesthesia. For more information see: Anesthesia Concerns

Williams syndrome is a genetic condition that affects many parts of the body. Signs and symptoms include mild to moderate intellectual disability; unique personality traits; distinctive facial features; and heart and blood vessel problems. Williams syndrome is caused by a person missing more than 25 genes from a specific area of chromosome 7 (a "deletion"). The loss of these genes contributes to the characteristic features. Although Williams syndrome is an autosomal dominant condition, most cases are not inherited and occur sporadically in people with no family history of Williams syndrome. Treatments are based on each person's signs and symptoms, as there is no cure at this time.

Treatment for people with Williams syndrome may be individualized depending on the symptoms and severity in each person. Management may include:

• Feeding therapy for infants with feeding problems
• Early intervention programs and special education programs for children with varying degrees of developmental disabilities
• Behavioral counseling and/or medications for attention deficit disorder and/or anxiety
• Surgery for certain heart abnormalities
• Medications or diet modifications for hypercalcemia
• Orthodontic appliances or other treatments for malocclusion of teeth
• Gonadotropin-releasing hormone agonist for early puberty

Management guidelines from the American Academy of Pediatrics: Health Care Supervision for Children With Williams Syndrome
Pediatrics, Vol. 107 No. 5 May 2001, pp. 1192-1204.
A statement of reaffirmation for this policy was published on September 1, 2005