Understanding Williams Syndrome

Williams syndrome also known as Williams–Beuren syndrome, idiopathic hypercalcemia, and supravalvar aortic stenosis syndrome is a genetic disorder caused by a deletion of about 26-28 genes on chromosome 7. Williams syndrome is a rare congenital disorder characterized by physical and development problems. Common features include, heart and blood vessel problems, irritability during infancy, dental and kidney abnormalities, hyperacusis (sensitive hearing), musculoskeletal problems and  characteristic "elfin-like" facial features. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Williams syndrome may also be associated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and/or other abnormalities.

Cardiac defects may include obstruction of proper blood flow from the lower right chamber (ventricle) of the heart to the lungs (pulmonary stenosis) or abnormal narrowing above the valve in the heart between the left ventricle and the main artery of the body (supravalvular aortic stenosis). Musculoskeletal abnormalities associated with Williams syndrome may include depression of the breastbone (pectus excavatum), abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), or an awkward gait. Although individuals with Williams syndrome may show competence in areas such as language, music and interpersonal relations, their IQs are usually low.

In Williams syndrome individuals, both the gene for elastin and an enzyme called LIM kinase are deleted. Both genes map to the same small area on chromosome 7. In normal cells, elastin is a key component of connective tissue, conferring its elastic properties. Mutation or deletion of elastin lead to the vascular disease observed in Williams syndrome. On the other hand, LIM kinase is strongly expressed in the brain, and deletion of LIM kinase is thought to account for the impaired visuospatial constructive cognition in Williams syndrome.

In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). However, familial cases have also been reported. Sporadic and familial cases are thought to result from deletion of genetic material from adjacent genes (contiguous genes) within a specific region of chromosome 7. The condition can typically be diagnosed by physical characteristics. The diagnosis can be confirmed by doing a test called fluorescent in situ hybridization (FISH). This is a lab test that labels DNA sequences with a chemical that lights up under ultraviolet light. This enables scientists to see if the gene is missing or not.

Other tests to help diagnose the condition can include a kidney ultrasound, blood pressure check, and an echocardiogram. Tests can also show high blood calcium levels, high blood pressure, slack joints, and unusual patterning in the iris of the eye.There is no cure for Williams syndrome. Treatment involves easing the symptoms connected to the syndrome. Narrowed blood vessels can be treated if they cause symptoms. Physical therapy and speech therapy can also be beneficial.

Treatment is usually based on the individual’s symptoms. There is no standard treatment protocol. Regular checkups are necessary to look at the cardiovascular system and track any possible problems.

Reference:

• Morris CA, Mervis CB. Williams syndrome. Cassidy and Allanson's Management of Genetic Syndromes. 2021 Feb 19:1021-38.
• Burn JO. Williams syndrome. Journal of Medical Genetics. 1986 Oct;23(5):389.

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