Williams syndrome (WS), also Williams–Beuren syndrome (WBS), is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed, particularly challenges with visual spatial tasks such as drawing. Verbal skills are relatively unaffected. Many people have an outgoing personality, a happy disposition, an openness to engaging with other people, increased empathy and decreased aggression. Medical issues with teeth, heart problems (especially supravalvular aortic stenosis), and periods of high blood calcium are common.
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. Typically, this occurs as a random event during the formation of the egg or sperm from which a person develops. In a small number of cases, it is inherited from an affected parent in an autosomal dominant manner. The different characteristic features have been linked to the loss of specific genes. The diagnosis is typically suspected based on symptoms and confirmed by genetic testing.
Interventions include special education programs and various types of therapy. Surgery may be performed to correct heart problems. Dietary changes or medications may be required for high blood calcium. The syndrome was first described in 1961 by New Zealander John C. P. Williams. Williams syndrome affects between one in 7,500 to 20,000 people at birth. Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease.
Signs and symptoms
The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy and low muscle tone. People with WS tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge. Microcephaly is present in one-third of affected individuals.
Most people with WS are highly verbal relative to their intelligence, and are often very sociable, having what has been described as a "cocktail party"-type personality. People with Williams syndrome hyperfocus on the eyes of others in social engagements.
Physical People with Williams syndrome 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 irregularitiesWong D, Ramachandra SS, Singh AK. Dental management of patient with Williams Syndrome - A case report. Contemp Clin Dent. 2015 Jul-Sep;6(3):418-20. and defective tooth enamel, and hormone problems, the most common being hypercalcemia. Hypothyroidism has been reported to occur in children, although no proof has been found of it occurring in adults; adults with WS have a higher risk of developing type 2 diabetes, with some cases apparent as young as 21 years old.
People with WS often have hyperacusia and phonophobia, which resembles noise-induced hearing loss; however, this may be due to a malfunctioning auditory nerve. People with WS also tend to demonstrate a love of music, and they appear significantly more likely to possess absolute pitch. Also, higher prevalences of left-handedness and left-eye dominance seem to occur.
Ophthalmologic issues are common among people with WS. Up to 75% of subjects in some studies have strabismus (ocular misalignment), particularly esotropia, due to inherent subnormal binocular visual function and cognitive deficits in visuospatial construction. People with WS have problems with visual processing, but this is related to difficulty in dealing with complex spatial relationships rather than depth perception per se.
Nervous system Because of missing multiple genes, many effects on the brain are seen, including abnormalities in the cerebellum, right parietal lobe, and left frontal cortical regions. This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in WS.
Frontal-cerebellar pathways, involved in behavioral timing, are often abnormally developed in people with WS, which may be related to their deficits in coordination and execution of fine motor tasks such as drawing and writing. In addition, people with WS often exhibit gross motor difficulties, including trouble walking downstairs, overactive motor reflexes (hyperreflexia), and hyperactive, involuntary movement of the eyes (nystagmus).
Williams syndrome is also noteworthy for exhibiting abnormalities in the parietal-dorsal areas of the neocortex, but not the ventral areas. The parietal-dorsal area handles visual processing that supports visual-spatial analysis of the environment, while the ventral is related to semantic recognition of visual stimuli, and the recognition of faces. Thus, people with WS are often able to visually identify and recognize whole objects, and refer to them by name, but struggle with visuospatial construction (seeing an object as being composed of many smaller parts, and recreating it) and orienting themselves in space.
People with WS are often affable and hyperverbal, demonstrating the decreased inhibition ability that stems from dorsal-frontal deficits. Some studies suggest that the amygdala of a person with Williams syndrome has greater volume than the average person's (though it is smaller than average in childhood). In general, neuroimaging studies demonstrate that people with WS have diminished amygdala reactivity in response to socially frightening stimuli (such as disapproving faces), but demonstrate hyperreactivity in the amygdala when presented with nonsocial fear stimuli (such as frightening animals). This may partially account for the apparent absence of social inhibition observed in people with the syndrome, as well as the prevalence of anxious symptoms (but see fear for details on the relationship between the amygdala and fear response). Also, some evidence indicates that people with WS exhibit amygdalal hyperactivity when viewing happy facial expressions. They are talkative and eager to please.
Increased volume and activation of the left auditory cortex has been observed in people with WS, which has been interpreted as a neural correlation of patients' rhythm propensity and fondness of music. Similar sizes of the auditory cortex have been previously reported only in professional musicians.
Development
The earliest observable symptoms of Williams syndrome include low birth weight, failure to thrive, breastfeeding difficulties, nocturnal irritability, and gastroesophageal reflux. Facial dysmorphies thought to be characteristic of the syndrome are also present early in development, as are heart murmurs. Research on the development of the syndrome suggests that congenital heart disease is typically present at an early age, often at the infant's first pediatric appointment. Heart problems in infancy often lead to the initial diagnosis of WS.
Developmental delays are present in most cases of WS, and include delay of language abilities and delayed motor-skill development. People with WS develop language abilities quite late relative to other children, with the child's first word often occurring as late as 3 years of age. Language abilities are often observed to be deficient until adolescence, in terms of semantics, morphology, and phonology, though not in vocabulary.
Williams syndrome is also marked by a delay in the development of motor skills. Infants with WS develop the ability to lift their heads and sit without support months later than typically developing children. These delays continue into childhood, where patients with WS are delayed in learning to walk. In young children, the observed motor delay is around 5–6 months, though some research suggests that children with WS have a delay in development that becomes more extreme with age. Children with motor delays as a result of WS are particularly behind in the development of coordination, fine motor skills such as writing and drawing, response time, and strength and dexterity of the arms. Impaired motor ability persists (and possibly worsens) as children with WS reach adolescence.
Adults and adolescents with Williams syndrome typically achieve a below-average height and weight, compared with unaffected populations. As people with WS age, they frequently develop joint limitations and hypertonia, or abnormally increased muscle tone. Hypertension, gastrointestinal problems, and genitourinary symptoms often persist into adulthood, as well as cardiovascular problems. Adults are typically limited in their ability to live independently or work in competitive employment settings, but this developmental impairment is attributed more to psychological symptoms than physiological problems.
Social and psychological
People with Williams syndrome report higher anxiety levels as well as phobia development, which may be associated with hyperacusis (high sensitivity to certain frequencies of sound). Compared with other children with delays, those with Williams syndrome display a significantly greater number of fears. 35% of these children met the DSM definition of having a phobia as compared with 1–4.3% for those with other types of developmental delays. Williams syndrome is also strongly associated with attention deficit hyperactivity disorder (ADHD) and related psychological symptoms such as poor concentration, hyperactivity, and social disinhibition.
Furthermore, cognitive abilities (IQs) of people with WMS typically range from mild to moderate levels of intellectual disability.Bellugi, U., Lichtenberger, L., Jones, W., Lai, Z., & George, M. S. (2000). I. The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. Journal of cognitive neuroscience, 12(Supplement 1), 7-29. Chicago One study of 306 children with Williams syndrome found IQ scores ranging from 40 to 112 with a mean of 69.32 (the mean IQ score of the general population is 100). IQ scores above this range have been reported in people with smaller genetic deletions. In particular, people with Williams syndrome experience challenges in visual-motor skills and visuospatial construction. Most affected people are unable to spatially orient themselves and many experience difficulty when given a task that requires even the most basic visual problem-solving. Many adults with Williams syndrome cannot complete a simple six-piece puzzle designed for young children, for example. These visuospatial deficits may be related to damage to the dorsal cortical pathway for visual processing.
Despite their physical and cognitive deficits, people with Williams syndrome exhibit impressive social and verbal abilities. WS patients can be highly verbal relative to their IQ. When children with Williams syndrome are asked to name an array of animals, they may well list a wild assortment of creatures such as a koala, saber-toothed cat, vulture, unicorn, sea lion, yak, ibex and Brontosaurus, a far greater verbal array than would be expected of children with IQs in the 60s. Some other strengths that have been associated with Williams syndrome are auditory short-term memory and facial recognition skills. The language used by people with Williams syndrome differs notably from unaffected populations, including people matched for IQ. People with Williams syndrome tend to use speech that is rich in emotional descriptors, high in prosody (exaggerated rhythm and emotional intensity), and features unusual terms and strange idioms.