Williams syndrome

Definitions & Key takeaways

Williams syndrome is a rare neurodevelopmental disorder 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; profound visuo-spatial impairments; and cardiovascular problems, such as supravalvular aortic stenosis and transient high blood calcium.
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Williams syndrome, also known as Williams-Beuren syndrome, is named after Dr. J.
C. P.
Williams who first described it. This is a chromosome disorder in which a small portion of chromosome 7 is deleted, which results in physical and developmental problems.
Now, our DNA is this humongous blueprint on how to make a human and it’s usually packaged up nicely into 46 chromosomes.
These 46 chromosomes come in 23 pairs - and each pair has one chromosome from each parent. Now, the individual chromosomes are shaped like an “X” with two short arms and two long arms linked together in the center by a centromere.
These two short arms are also referred to as p arms from the French term “petit” meaning small. What's more, the two long arms are also referred to as q arms, since 'q' follows 'p' in the alphabet.
In Williams syndrome, about 26 to 28 genes, including the elastin gene (ELN) on the long arm of chromosome 7 are missing due to a microdeletion.
In most cases, this occurs randomly during the formation of sex cells in one of the parents. So a sperm cell or an ovum can potentially carry this microdeletion on the long arm of its chromosome 7 and go on to fuse with another sex cell - forming a new organism which has the microdeletion.
Rarely, the cause of Williams syndrome can also be an inherited in an autosomal dominant fashion - so when a person with Williams syndrome has children, there is a 50% chance they’ll pass down their own microdeletion to the offspring.
Now, the precise location of the microdeletion is at band 7q11.23, just like the directions to an address: 7 stands for chromosome 7, 'q' refers to the long arm, 11.23 refers to the specific region on the chromosome- and then it gets very specific: region 1, band 1, sub-band 2, sub-sub-band 3.
This section of DNA spans about 26 to 28 genes and 1.5 to 1.8 million base pairs - so this is considered a microdeletion, because we’re talking about less than 5 million base pairs.
Even though this region is pretty small, it codes for some very important genes, one of which is the elastin gene, which is responsible for the production of elastin protein which allows many tissues in the body to resume their shape after stretching or contracting.
So the symptoms of Williams syndrome are linked to connective tissue abnormalities resulting from these missing genes. For example, the loss of the elastin gene leads to a broad forehead, flat nasal bridge, periorbital puffiness, short upturned nose, long medial cleft, full lips, and wide mouth that in combination give an "elfin" like appearance.
Other connective tissue abnormalities are the narrowing of major blood vessels, which predisposes to hypertension. When the pulmonary arteries narrow, this causes pulmonary artery stenosis.
When the aorta narrows just above the aortic valve, this causes supravalvular aortic stenosis. And both aortic and pulmonary stenosis can cause heart murmurs and hypertension.
Of the 26 to 28 missing genes, some are thought to play a role in the particular psychological traits of people with Williams syndrome.
Basically, individuals with Williams syndrome have a “cocktail party” personality, meaning they’re very talkative, outgoing, and have strong language skills.
On the flip side, they also experience cognitive impairment, weak visual motor, and visual-spatial abilities, as well as developmental delay, anxiety, phobias, and obsessive-compulsive traits.
Individuals with Williams syndrome also have an increased sensitivity to vitamin D, which plays a role in the intestinal absorption of calcium.
So this means more calcium gets absorbed into the blood, and individuals have symptoms of hypercalcemia, like irritability, loss of appetite, and vomiting.
The extra calcium is eventually excreted in the urine, where it can deposit and form kidney stones. Now, the diagnosis of Williams syndrome can be suspected by the clinical features especially the "elfin" like appearance and by the very talkative, and outgoing personality.
Diagnosis can be confirmed with microarray analysis, which is a test that can detect small deletions or amplifications of genetic material.
An individual's DNA sample and a control sample are marked with different fluorescent colors and compared on a microchip containing many probes that bind to specific regions of the DNA.
Another test that can be done is the fluorescence in situ hybridization or FISH. This involves a fluorescently labeled probe made of DNA that’s complementary to the 7q elastin gene region.
In a normal cell, the probes can bind to both chromosome 7q elastin gene region so you would expect two bright spots in the microscope under fluorescent lighting.
If a 7p elastin gene region deletion is present, though, one of those 7p regions is missing, so you’ll only see a single bright spot.
Now because Williams syndrome is caused by genetic microdeletion, there’s no known cure. So management focuses on treating congenital heart defects through surgical repair, hypertension with antihypertensive medication, a vitamin D and calcium restricted diet - to lower the calcium levels in blood.
Additional treatment involves physical, language and occupational therapy in order to maximize their development, personal growth, and independence.
All right as a quick recap, Williams syndrome is a genetic condition where part of the long arm of chromosome 7 is micro-deleted, specifically region 7q11.23.
Williams syndrome is characterized by an "elfin" like facial appearance, outgoing and talkative personality, congenital cardiovascular defects, cognitive impairment, hypertension, and hypercalcemia.
Additional findings include neurodevelopmental delay, and others. Diagnosis is based on microarray analysis and fluorescence in situ hybridization or FISH to find chromosomal abnormalities, and treatment is based on treating life-threatening conditions after birth and early intervention education.