Williams syndrome

Williams syndrome is caused by a genetic abnormality, specifically a deletion of about 27 genes from the long arm of one of the two chromosome 7s.^[2][4] Typically, this occurs as a random event during the formation of the egg or sperm from which a person develops.^[2] In a small number of cases, it is inherited from an affected parent in an autosomal dominant manner.^[2] The different characteristic features have been linked to the loss of specific genes.^[2] The diagnosis is typically suspected based on symptoms and confirmed by genetic testing.^[1]


Interventions to support people with WS includes special education programs and various types of therapy.^[1] Surgery may be done to correct heart problems.^[1] Dietary changes or medications may be required for high blood calcium.^[1] The syndrome was first described in 1961 by New Zealander John C. P. Williams.^[5][6] Williams syndrome affects between one in 20,000 and one in 7,500 people at birth.^[4] Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease.^[3]

Diagnosis[edit]

According to the Williams Syndrome Association, its diagnosis begins with the recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of WS include puffiness around the eyes, a long philtrum, and a stellate pattern in the iris. Physiological symptoms that often contribute to a WS diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, and feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.^[52]


If a physician suspects a case of WS, the diagnosis is confirmed using one of two possible genetic tests: Micro-array analysis or the fluorescent in situ hybridization test, which examines chromosome 7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with WS lack half of the 7q11.23 region of chromosome 7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of WS.^[52] This confirmatory genetic test has been validated in epidemiological studies and has been demonstrated to be a more effective method of identifying WS than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).^[53]


Reliance on facial features to identify WS may cause a misdiagnosis of the condition. Among the more reliable features suggestive of WS are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long, smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Even with significant clinical experience, reliably identifying Williams syndrome based on facial features alone is difficult.^[25]


This is particularly the case in individuals of non-white backgrounds, where typical WS facial features (such as full lips) are more prevalent. ^[54]

Treatment[edit]

No cure for Williams syndrome has been found. Suggested treatments include avoidance of extra calcium and vitamin D, and treating high levels of blood calcium. Blood-vessel narrowing can be a significant health problem and is treated on an individual basis. Physical therapy is helpful to patients with joint stiffness and low muscle tone. Developmental and speech therapy can also help children and increase the success of their social interactions. Other treatments are based on a patient's particular symptoms.^[8]


The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with WS. Other recommended assessments include ophthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood-pressure measurement, developmental and growth evaluation, orthopedic assessments on joints and muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.^[55]


Behavioral treatments have been shown to be effective. In regard to social skills, it may be effective to channel their nature by teaching basic skills. Some of these are the appropriate way to approach someone, how and when to socialize in settings such as school or the workplace, and warning of the signs and dangers of exploitation. For phobias, cognitive-behavioral approaches, such as therapy, are the recommended treatments. One of the things to be careful of with this approach is to make sure that the patients' "charming" nature does not mask any underlying feelings.


Perhaps the most effective treatment for those with WS is music. Those affected have shown relative strength in regards to music, albeit only in pitch and rhythm tasks. Not only do they show strength in the field, but also a particular fondness for it. Music may help with the internal and external anxiety with which these people are more likely to be afflicted.^[56] Notably, the typical person processes music in the superior temporal and temporal gyri. Those with WS have reduced activation in these areas, but an increase in the right amygdala and cerebellum.


People affected by WS are supported by multiple organizations, including the Canadian Association for Williams Syndrome and the Williams Syndrome Registry.^[57]

Epidemiology[edit]

Williams syndrome has historically been estimated to occur in roughly one in every 20,000 live births,^[23] but more recent epidemiological studies have placed the occurrence rate at closer to one in every 7,500 live births, a significantly larger prevalence. As increasing evidence suggests WS is more common than originally noted (about 6% of all genetic cases of developmental disability), researchers have begun to hypothesize a previous underdiagnosis of the syndrome.^[58] One suggested factor in the increase in epidemiological prevalence estimates is that a substantial minority of individuals with the genetic markers of WS lack the characteristic facial features or the diminished intelligence considered to be diagnostic of the syndrome, and often are not immediately recognized as having the syndrome.^[9][59]