Williams syndrome

The signs and symptoms of Williams syndrome can vary, but generally include:^[1][2]

• mild to moderate intellectual disability;
• a distinctive facial appearance;
• and a unique personality that combines over-friendliness and high levels of empathy with anxiety.

People with Williams syndrome typically have difficulty with tasks such as drawing and assembling puzzles. They tend to do well on tasks that involve spoken language, music, and learning by repetition.^[1]

Facial features common in young children with Williams syndrome include a 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. Dental problems are common and may include small, widely spaced teeth and teeth that are crooked or missing.^[1]

People with Williams syndrome often have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common.^[1]

The most significant medical problem associated with Williams syndrome is a form of heart disease called supravalvular aortic stenosis (SVAS). SVAS is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, it can lead to shortness of breath, chest pain, and heart failure. The presence of other heart and blood vessel problems has also been reported.^[1]

Additional signs and symptoms of Williams syndrome may include:^[1]

 

• abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin;
• increased calcium levels in the blood (hypercalcemia) in infancy;
• developmental delays;
• problems with coordination;
• short stature;
• vision and eye problems;
• digestive problems; and
• urinary problems.

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.^[1]

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.^[1] The relationship between some of the other deleted genes and the features of Williams syndrome is not yet known.^[1]

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.^[1] Williams syndrome is caused by a person missing more than 25 genes from a specific area of chromosome 7 (a "deletion").^[1][3] The loss of these genes contributes to the characteristic features.^[1] 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.^[1][2]

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.^[1] 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.^[4]

 

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.^[4]   

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.^[3] 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.^[4]