Williams syndrome

Other Names: Williams-Beuren syndrome; WBS; WMS; Deletion 7q11.23; Monosomy 7q11.23

Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems.

Epidemiology

Williams syndrome affects an estimated 1 in 7,500 to 10,000 people.

Cause

Williams syndrome is caused by the deletion of genetic material from a specific region of chromosome 7. The deleted region includes 26 to 28 genes, and researchers believe that a loss of several of these genes probably contributes to the characteristic features of this disorder.

CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ELN gene is associated with the connective tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis) found in many people with this disease. Studies suggest that deletion of CLIP2, GTF2I, GTF2IRD1, LIMK1, and perhaps other genes may help explain the characteristic difficulties with visual-spatial tasks, unique behavioral characteristics, and other cognitive difficulties seen in people with Williams syndrome. Loss of the GTF2IRD1 gene may also contribute to the distinctive facial features often associated with this condition.

Researchers believe that the presence or absence of the NCF1 gene on chromosome 7 is related to the risk of developing hypertension in people with Williams syndrome. When the NCF1 gene is included in the part of the chromosome that is deleted, affected individuals are less likely to develop hypertension. Therefore, the loss of this gene appears to be a protective factor. People with Williams syndrome whose NCF1 gene is not deleted have a higher risk of developing hypertension.

The relationship between other genes in the deleted region of chromosome 7 and the signs and symptoms of Williams syndrome is under investigation or unknown.

Inheritance

Most cases of Williams syndrome are not inherited but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases occur in people with no history of the disorder in their family.

Williams syndrome is considered an autosomal dominant condition because one copy of the altered chromosome 7 in each cell is sufficient to cause the disorder. In a small percentage of cases, people with Williams syndrome inherit the chromosomal deletion from a parent with the condition.

Signs and symptoms

The signs and symptoms of Williams syndrome can vary, but generally include:

• 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.

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.

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.

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.

Additional signs and symptoms of Williams syndrome may include:

• 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.

Diagnosis

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.

Tests for Williams syndrome include:

• Blood pressure check
• Blood test for a missing piece of chromosome 7 (FISH test)
• Urine and blood tests for calcium level
• Echocardiography combined with Doppler ultrasound
• Kidney ultrasound

Treatment

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

Prognosis

Most people with Williams syndrome: Have some intellectual disability. Will not live as long as normal due to the various medical issues and other possible complications. Require full-time caregivers and often live in supervised group homes.

Possible Complications Complications may include:

• Calcium deposits in the kidney and other kidney problems
• Death (in rare cases from anesthesia)
• Heart failure due to narrowed blood vessels
• Pain in the abdomen

NIH genetic and rare disease info

• NIH info on Williams syndrome

Williams syndrome is a rare disease.

Williams syndrome Resources
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