Williams syndrome

FANI Williams syndrome (WS or WMS; or WBS) is a rare neurodevelopmental disorder caused by a deletion of about 26 genes from the long arm of chromosome 7.[1] 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 8000 to 1 in 20,000 ( twenty) births. Babies with Williams syndrome may have a low birth weight and experience difficulty feeding and gaining weight. It's usually clear there are developmental problems - children with the syndrome may not talk until the age of three. Nervous system DIANA Because of the multiple genes that are missing in people with Williams syndrome, there are many effects on the brain, including abnormalities in the cerebellum, right parietal cortex, and left frontal cortical regions. This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing. Frontal-cerebellar pathways are involved in behavioral timing, and the parietal-dorsal areas of the neocortex handle visual processing that supports visual-spatial analysis of the environment (but not faces). People are often affable and hyperverbal which demonstrates the decreased inhibition ability that stems from dorsalfrontal deficits.[18] There have also been studies that show that the amygdala of a person with Williams syndrome has greater volume than the average person's. The amygdala controls a human's sense of fear and it can be seen why WS individuals can so willingly talk to anyone, including strangers. Studies in 2010 showed an increased volume and activation of the left auditory cortex in people with Williams Syndrome, which has been interpreted as a neural correlate of their

rhythm propensity and fondness of music. Similar sizes of the auditory cortex have been previously reported only in professional musicians. Cause FANI Williams syndrome is caused by the deletion of genetic material from a region 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. 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 visualspatial 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. Facial appearance DIANA SLIDE 2 SI 3

Most young children with Williams syndrome are described as having similar facial features. These features which tend to be recognized by only a trained geneticist or birth defects specialist, include a small upturned nose, long philtrum (upper lip length), wide mouth, full lips, small chin, and puffiness around the eyes. SLIDE 3 Blue and green-eyed children with Williams syndrome can have a prominent "starburst" The eyes have small opening slits (small papebral fissures or eye slits). Facial features become more apparent with age. There may be some degree of learning disability and problems with coordination and balance. High energy levels mean children with the syndrome talk excessively, often in an inappropriate, adult manner (referred to as cocktail party personality), and will be overactive, making sleep a real challenge.

Heart and blood vessel problems FANI SLIDE 4 The majority of individuals with Williams syndrome have some type of heart or blood vessel problem. Typically, there is narrowing in the aorta (producing supravalvular aortic stenos is SVAS), or narrowing in the pulmonary arteries. There is a broad range in the degree of narrowing, ranging from trivial to severe (requiring surgical correction of the defect). Since there is an increased risk for development of blood vessel narrowing or high blood pressure over time, periodic monitoring of cardiac status is necessary. Hypercalcemia (elevated blood calcium levels) DIANA SLIDE 5 Some young children have elevations in their blood calcium level. The true frequency and cause of this problem is unknown. When hypercalcemia is present, it can cause extreme irritability or "colic-like" symptoms. Occasionally medical treatment is needed. In most cases, the problem resolves on its own during childhood, but lifelong abnormality in calcium or Vitamin D metabolism may exist and should be monitored. Low birth-weight / low weight gain DIANA Most children have a slightly lower birth-weight than their brothers or sisters. Slow weight gain, especially during the first several years of life, is also a common problem and many children are diagnosed as "failure to thrive". Adult stature is slightly smaller than average. Feeding problems FANI SLIDE 6 Many infants and young children have feeding problems. These problems have been linked to low muscle tone, severe gag reflex, poor suck/swallow, tactile defensiveness etc. Feeding difficulties tend to resolve as the children get older.

Irritability (colic during infancy) FANI Many infants with Williams syndrome have an extended period of colic or irritability. This typically lasts from 4 to 10 months of age, then resolves. It is sometimes attributed to hypercalcemia. Abnormal sleep patterns with delayed acquisition of sleeping through the night may be associated with the colic. Dental abnormalities SLIDE 7 DIANA Slightly small, widely spaced teeth are common in children with Williams syndrome. They also may have a variety of abnormalities of occlusion (bite), tooth shape or appearance. Most of these dental changes are readily amenable to orthodontic correction. Kidney abnormalities There is a slightly increased frequency of problems with kidney structure and/or function. Hernias Inguinal (groin) and umbilical hernias are more common in Williams syndrome than in the general population. Hyperacusis (sensitive hearing) FANI Children with Williams syndrome often have more sensitive hearing than other children; Certain frequencies or noise levels can be painful an/or startling to the individual. This condition often improves with age.

Musculoskeletal problems Young children with Williams syndrome often have low muscle tone and joint laxity. As the children get older, joint stiffness (contractures) may develop. Physical therapy is very helpful in improving muscle tone, strength and joint range of motion.

Overly friendly (excessively social) personality Individuals with Williams syndrome have a very endearing personality. They have a unique strength in their expressive language skills, and are extremely polite. They are typically unafraid of strangers and show a greater interest in contact with adults than with their peers. Developmental delay, learning disabilities and attention deficit SLIDE 8 DIANA Most people with this syndrome have some degree of intellectual handicap. Young children often experience developmental delays; milestones such as walking, talking and toilet training are often achieved somewhat later than is considered normal. Distractibility is a common problem in mid-childhood, which appears to get better as the children get older. Older children and adults often demonstrate intellectual "strengths and weaknesses." There are some intellectual areas (such as speech, long term memory, and social skills) in which performance is quite strong, while other intellectual areas (such as fine motor and spatial relations) are significantly deficient. Treatment FANI 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.[5] Guidelines published by the American Academy of Pediatrics include cardiology evaluations, developmental and psychoeducational assessment, and many other examination, laboratory, and anticipatory guidance recommendations.