Williams syndrome
Encyclopedia
Williams syndrome is a rare neurodevelopmental disorder characterized by a distinctive, "elf
in" 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
.
It is caused by a deletion of about 26 genes from the long arm of chromosome 7. 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.
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 murmur
s 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.
Williams syndrome is notable in that respect in that it represents a double dissociation between verbal and spatial processing. Williams patients can be highly verbal. When children with Williams syndrome are asked to name an array of animals, they may well list such a wild assortment of creatures as a koala
, saber-toothed tiger, vulture
, unicorn
, sea lion
, yak
, ibex and "Brontosaurus rex".
Some cultural historians believe that the adjective "elfin" came to be used to describe the facial features of people with Williams syndrome because, before Williams syndrome's scientific cause was understood, people believed that sufferers of the syndrome, who have very charming and extraordinarily kind personalities in comparison to most people, were gifted with extraordinary, even magical, powers. This is often believed to be the origin of the folklore of elves, fairies and other forms of the 'good people' or 'wee folk' present in English folklore
. Even though they are often described in the literature as "elfin-faced", Steven Pinker
says in The Language Instinct
that to him they often appear more like Mick Jagger
".
, right parietal cortex, and left frontal cortical regions. This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in Williams syndrome. 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 with Williams syndrome are often affable and hyperverbal – often blurting – which demonstrates the decreased inhibition ability that stems from dorsal-frontal deficits. There have also been studies that show that the amygdala
of a person with Williams syndrome has greater volume than the average person's, and given that the amygdala controls a human's sense of fear, 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.
s, and researchers believe that the loss of several of these genes probably contributes to the characteristic features of this disorder. , ELN
, , , and 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.
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.
Elf
An elf is a being of Germanic mythology. The elves were originally thought of as a race of divine beings endowed with magical powers, which they use both for the benefit and the injury of mankind...
in" facial appearance, along with a low nasal bridge
Nasal bridge
The nasal bridge is the name given to the upper, bony part of the nose, overlying the nasal bones.A lower or higher than average nasal bridge can be a sign of various genetic disorders, such as fetal alcohol syndrome. A flat nasal bridge can be a sign of Down syndrome, Fragile X syndrome, and Fetal...
; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language
Language
Language may refer either to the specifically human capacity for acquiring and using complex systems of communication, or to a specific instance of such a system of complex communication...
skills; and cardiovascular problems, such as supravalvular aortic stenosis and transient hypercalcaemia
Hypercalcaemia
Hypercalcaemia is an elevated calcium level in the blood. . It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists...
.
It is caused by a deletion of about 26 genes from the long arm of chromosome 7. The syndrome was first identified in 1961 by Dr. J. C. P. Williams
J. C. P. Williams
J.C.P. Williams was a New Zealand cardiologist known for discovering what is now called Williams syndrome in 1961, while working as the Registrar at Greenlane Hospital in Auckland....
of New Zealand and has an estimated prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of 1 in 7,500 to 1 in 20,000 births.
Signs and symptoms
Hyperfocus
Hyperfocus is an intense form of mental concentration or visualization that focuses consciousness on a narrow subject, separate from objective reality and onto subjective mental planes, daydreams, concepts, fiction, the imagination, and other objects of the mind...
on the eyes of others in social engagements. Patients tend to have widely spaced teeth, a long philtrum
Philtrum
The philtrum , is a medial cleft common to many mammals, extending from the nose to the upper lip, and, together with a glandular rhinarium and slit-like nostrils, is believed to constitute the primitive condition for mammals in general...
, and flattened nasal bridge.
Individuals with Williams syndrome also experience many cardiac problems, commonly heart murmur
Heart murmur
Murmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
s 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
Colic
Colic is a form of pain which starts and stops abruptly. Types include:*Baby colic, a condition, usually in infants, characterized by incessant crying*Renal colic, a pain in the flank, characteristic of kidney stones...
, abdominal pain and diverticulitis
Diverticulitis
Diverticulitis is a common digestive disease particularly found in the large intestine. Diverticulitis develops from diverticulosis, which involves the formation of pouches on the outside of the colon...
, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel
Tooth enamel
Tooth enamel, along with dentin, cementum, and dental pulp is one of the four major tissues that make up the tooth in vertebrates. It is the hardest and most highly mineralized substance in the human body. Tooth enamel is also found in the dermal denticles of sharks...
, as well as hormone problems, the most common being hypercalcemia (elevated calcium levels in the blood). Hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
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
Hyperacusis
Hyperacusis is a health condition characterized by an over-sensitivity to certain frequency ranges of sound...
and phonophobia which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve
Cochlear nerve
The cochlear nerve is a nerve in the head that carries signals from the cochlea of the inner ear to the brain...
. However, individuals with WS can also tend to demonstrate a love of music, and appear significantly more likely to possess perfect pitch
Absolute pitch
Absolute pitch , widely referred to as perfect pitch, is the ability of a person to identify or re-create a given musical note without the benefit of an external reference.-Definition:...
. There also appears to be a higher prevalence of left-handedness and left-eye dominance
Ocular dominance
Ocular dominance, sometimes called eye dominance or eyedness, is the tendency to prefer visual input from one eye to the other. It is somewhat analogous to the laterality of right or left handedness; however, the side of the dominant eye and the dominant hand do not always match...
. Individuals with Williams syndrome also report higher anxiety levels as well as phobia
Phobia
A phobia is a type of anxiety disorder, usually defined as a persistent fear of an object or situation in which the sufferer commits to great lengths in avoiding, typically disproportional to the actual danger posed, often being recognized as irrational...
development, which may be associated with hyperacusis.
Furthermore, individuals with Williams syndrome have problems with visual processing
Visual processing
Visual processing is the sequence of steps that information takes as it flows from visual sensors to cognitive processing. The sensors may be zoological eyes or they may be cameras or sensor arrays that sense various portions of the electromagnetic spectrum....
, but this is related to difficulty in dealing with complex spatial relationships rather than to issues with depth perception
Depth perception
Depth perception is the visual ability to perceive the world in three dimensions and the distance of an object. Depth sensation is the ability to move accurately, or to respond consistently, based on the distances of objects in an environment....
.
In an experiment, a group of children with Williams syndrome showed no signs of inherent racial bias, unlike children without the syndrome.
Williams syndrome is notable in that respect in that it represents a double dissociation between verbal and spatial processing. Williams patients can be highly verbal. When children with Williams syndrome are asked to name an array of animals, they may well list such a wild assortment of creatures as a koala
Koala
The koala is an arboreal herbivorous marsupial native to Australia, and the only extant representative of the family Phascolarctidae....
, saber-toothed tiger, vulture
Vulture
Vulture is the name given to two groups of convergently evolved scavenging birds, the New World Vultures including the well-known Californian and Andean Condors, and the Old World Vultures including the birds which are seen scavenging on carcasses of dead animals on African plains...
, unicorn
Unicorn
The unicorn is a legendary animal from European folklore that resembles a white horse with a large, pointed, spiraling horn projecting from its forehead, and sometimes a goat's beard...
, sea lion
Sea Lion
Sea lions are pinnipeds characterized by external ear-flaps, long fore-flippers, the ability to walk on all fours, and short thick hair. Together with the fur seal, they comprise the family Otariidae, or eared seals. There are six extant and one extinct species in five genera...
, yak
Yak
The yak, Bos grunniens or Bos mutus, is a long-haired bovine found throughout the Himalayan region of south Central Asia, the Tibetan Plateau and as far north as Mongolia and Russia. In addition to a large domestic population, there is a small, vulnerable wild yak population...
, ibex and "Brontosaurus rex".
Some cultural historians believe that the adjective "elfin" came to be used to describe the facial features of people with Williams syndrome because, before Williams syndrome's scientific cause was understood, people believed that sufferers of the syndrome, who have very charming and extraordinarily kind personalities in comparison to most people, were gifted with extraordinary, even magical, powers. This is often believed to be the origin of the folklore of elves, fairies and other forms of the 'good people' or 'wee folk' present in English folklore
English folklore
English folklore is the folk tradition which has developed in England over a number of centuries. Some stories can be traced back to their roots, while the origin of others is uncertain or disputed...
. Even though they are often described in the literature as "elfin-faced", Steven Pinker
Steven Pinker
Steven Arthur Pinker is a Canadian-American experimental psychologist, cognitive scientist, linguist and popular science author...
says in The Language Instinct
The Language Instinct
The Language Instinct is a book by Steven Pinker for a general audience, published in 1994. In it, Pinker argues that humans are born with an innate capacity for language. In addition, he deals sympathetically with Noam Chomsky's claim that all human language shows evidence of a universal grammar...
that to him they often appear more like Mick Jagger
Mick Jagger
Sir Michael Philip "Mick" Jagger is an English musician, singer and songwriter, best known as the lead vocalist and a founding member of The Rolling Stones....
".
Nervous system
Because of the multiple genes that are missing in people with Williams syndrome, there are many effects on the brain, including abnormalities in the cerebellumCerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
, right parietal cortex, and left frontal cortical regions. This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in Williams syndrome. 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 with Williams syndrome are often affable and hyperverbal – often blurting – which demonstrates the decreased inhibition ability that stems from dorsal-frontal deficits. There have also been studies that show that the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
of a person with Williams syndrome has greater volume than the average person's, and given that the amygdala controls a human's sense of fear, 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
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 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, and researchers believe that the loss of several of these genes probably contributes to the characteristic features of this disorder. , ELN
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
, , , and 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
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
, is associated with the connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis
Aortic valve stenosis
Aortic valve stenosis is a disease of the heart valves in which the opening of the aortic valve is narrowed. The aortic valve is the valve between the left ventricle of the heart and the aorta, which is the largest artery in the body and carries the entire output of blood.-Pathophysiology:The...
and supravalvular pulmonary stenosis
Pulmonary valve stenosis
Pulmonary valve stenosis is a heart valve disorder in which outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve. This results in the reduction of flow of blood to the lungs. Valvular pulmonic stenosis accounts for 80% of right ventricular outflow...
) 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.