Williams syndrome

Williams syndrome (WS or WMS; also Williams–Beuren syndrome or WBS) is a rare neurodevelopmental disorder caused by a deletion of about 26 genes from the long arm of chromosome 7. It is characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as supravalvular aortic stenosis and transient hypercalcaemia. The syndrome was first identified in 1961 by Dr. J. C. P. Williams of New Zealand and has an estimated prevalence of 1 in 7,500 to 1 in 20,000 births.

Cause

Williams syndrome is caused by the deletion of genetic material from the region q11.23 of chromosome 7. The deleted region includes more than 25 genes, and researchers believe that the 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, which codes for the protein elastin, is associated with the connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis and supravalvular pulmonary stenosis) found in many people with this syndrome. Studies suggest that deletion of LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, there is evidence that the loss of several of these genes, including CLIP2, may contribute to the unique behavioral characteristics, learning disabilities, and other cognitive difficulties seen in Williams syndrome.

Treatment

There is no cure for Williams syndrome. Suggestions include avoiding taking extra calcium and vitamin D, and treating high levels of blood calcium, if present. Blood vessel narrowing can be a significant health problem as well, and is treated on an individual basis. Physical therapy is helpful to patients with joint stiffness. Developmental and speech therapy can also help these children (for example, verbal strengths can help make up for other weaknesses). Other treatments are based on a patient's particular symptoms. Guidelines published by the American Academy of Pediatrics include cardiology evaluations, developmental and psychoeducational assessment, and many other examination, laboratory, and anticipatory guidance recommendations.

Signs and symptoms

The most common symptoms of Williams syndrome are mental disability, heart defects, and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy and low muscle tone. Most individuals with Williams syndrome are highly verbal and overly sociable, having what has been described as a "cocktail party" type personality, and exhibit a remarkable blend of cognitive strengths and weaknesses. Individuals with WS hyperfocus on the eyes of others in social engagements. Patients tend to have widely spaced teeth, a long philtrum, and flattened nasal bridge. Individuals with Williams syndrome also experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels as well as supravalvular aortic stenosis. Other symptoms may include gastrointestinal problems, such as severe or prolonged colic, abdominal pain and diverticulitis, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel, as well as hormone problems, the most common being hypercalcemia (elevated calcium levels in the blood). Hypothyroidism has been reported to occur in children, although there is no proof of it occurring in adults; diabetes has been reported to occur in adults with WS as young as 21 years old.

Individuals with Williams syndrome often have hyperacusis and phonophobia which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve. However, individuals with WS can also tend to demonstrate a love of music, and appear significantly more likely to possess perfect pitch. There also appears to be a higher prevalence of left-handedness and left-eye dominance. Individuals with Williams syndrome also report higher anxiety levels as well as phobia development, which may be associated with hyperacusis.

Furthermore, individuals with Williams syndrome have problems with visual processing, but this is related to difficulty in dealing with complex spatial relationships rather than to issues with depth perception.

In an experiment, a group of children with Williams syndrome showed no signs of inherent racial bias, unlike children without the syndrome.