Diagnosis: Williams syndrome

Williams syndrome, also known as Williams–Beuren syndrome, is a rare genetic disorder characterized by delayed growth before and after birth (prenatal and postnatal growth retardation), short stature, varying degrees of intellectual disability, and distinct facial features that typically become more pronounced with age. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually open, and a broad nasal bridge with nostrils that flare forward (“anteverted nares”). Affected individuals may also have unusually short palpebral fissures (eyelid openings), wide eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur, including abnormally small, poorly developed teeth (hypodontia) with small, slender roots.

Children with Williams syndrome usually have a friendly, sociable, and talkative personality. Appropriate use of language and vocabulary may be enhanced in some affected children. Some children have average intelligence but severe learning disabilities. Hyperactivity and attention deficit are also common, although most affected individuals have good long‑term memory. Some affected individuals may have visual problems — for example, they may tend to view a picture in parts rather than as a whole.

In older children and adults with Williams syndrome, progressive joint problems may develop, limiting their range of motion. Skeletal abnormalities may also be present, such as curvature of the spine backwards (lordosis), front‑to‑back curvature (kyphosis), and side‑to‑side curvature (scoliosis). Some affected individuals may have a sunken chest (pectus excavatum) and inward deviation of the big toe toward the other toes (hallux valgus). Skeletal and joint abnormalities may result in an abnormal gait. As affected individuals age, skeletal abnormalities may worsen.

Additional abnormalities may occur in some individuals with Williams syndrome, including kidney abnormalities, chronic urinary tract infections, underdeveloped (hypoplastic) thyroid gland, and umbilical or inguinal hernia.

In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons. However, familial cases have also been recorded. It is thought that both sporadic and familial cases are caused by a deletion of genetic material from adjacent genes in a specific region of chromosome 7 (7q11.23).

Diagnosis

Williams syndrome is a rare disorder that affects males and females equally. The prevalence of this condition is approximately one in 10,000–20,000 live births.

Diagnosis is performed based on the described symptoms and through genetic testing, which identifies deletions in genes on chromosome 7.

It appears that most cases of Williams syndrome occur spontaneously. However, some familial cases of the disorder have also been reported. Ongoing research suggests that both sporadic and familial Williams syndrome result from a deletion of genetic material from neighboring genes located on the long arm (q) of chromosome 7 (7q11.23). This chromosomal region has been referred to as the “Williams–Beuren syndrome chromosome region 1 (WBSCR1).”

According to researchers, 28 genes in the chromosomal region 7q11.23 may play a causal role in Williams syndrome, including genes known as the ELN gene (elastin), LIMK1 gene (or LIM kinase‑1), and RFC2 gene (replication factor C, subunit 2). The LIMK1 gene is believed to contribute to the visuospatial problems associated with Williams syndrome.

In familial cases, Williams syndrome is inherited as an autosomal dominant trait. Genetic disorders are determined by two genes — one inherited from the father and one from the mother. Dominant genetic disorders occur when only one copy of the abnormal gene is needed for the disease to appear. The abnormal gene may be inherited from one parent, or it may result from a new mutation in the affected individual. The risk of passing the abnormal gene from an affected parent to their child is 50% for each pregnancy, regardless of the child’s sex.

Hypercalcemia, which is associated with some cases of Williams syndrome, may occur due to abnormal sensitivity to vitamin D.

The diagnosis of Williams syndrome can be confirmed through a thorough clinical examination, including a detailed patient history and specialized blood tests that may reveal elevated calcium levels. Another test, known as fluorescence in‑situ hybridization (FISH), can be used to determine whether a deletion of the elastin gene on chromosome 7 is present. This deletion is believed to occur in the majority of individuals with Williams syndrome.

Therapy

Treatment of this syndrome is not possible because it is a genetically determined disorder. Only the symptoms listed below can therefore be alleviated.

Infants with Williams syndrome who have elevated calcium levels in the blood may be placed on a diet that restricts vitamin D intake. Calcium intake may also be limited. In children with severe hypercalcemia, temporary treatment with corticosteroids (e.g., prednisone) may be considered. After reaching approximately 12 months of age, calcium levels usually return to normal, even in untreated infants. It is recommended that children with Williams syndrome also be examined by a doctor specializing in endocrine disorders (an endocrinologist).

Affected children who have symptoms related to heart defects should undergo comprehensive evaluation in a hospital familiar with these rare congenital heart diseases. Specialized tests (i.e., ECG, echocardiogram, or cardiac catheterization) may be performed to determine the severity and precise location of congenital heart defects. Some children with Williams syndrome who have severe heart defects may require surgical treatment to correct the defect.

Centers for children with developmental disabilities and special education services in schools may be beneficial for children with Williams syndrome in achieving their personal potential. A supportive team approach may also be helpful, including speech and language therapy, occupational and physical therapy, social services, and/or vocational training. Music therapy has been advocated — although not proven — as providing better learning and relief from anxiety in individuals with Williams syndrome.

Genetic counseling may be beneficial for individuals with Williams syndrome and their families. Other treatment is symptomatic and supportive.

Williams syndrome

General

Diagnosis

Therapy

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