Prader-Willi syndrome (PWS)
Prader-Willi syndrome (pronounced PRAH-der WILL-ee), also known as PWS, is a condition with many different symptoms that affects appetite, growth, metabolism, cognitive function, and behavior.
What causes PWS?
PWS is caused by variants variant A change in the standard “spelling” of a gene. Genetic variants may result in serious health problems or be “silent” with no negative health effects. , or changes, located in a specific region of chromosome 15. Chromosome 15 plays an important role in the functionality of the hypothalamus hypothalamus A small part of the brain that has an important role in controlling many bodily functions including the release of hormones from the pituitary gland. The MC4R pathway is located here. and regulation of your appetite. This variant can cause parts of the hypothalamus to not work properly, which prevents the brain from understanding if you’re full. As a result, people with PWS almost always feel hungry.
What are the key clinical features of PWS?
While different people with PWS will have different symptoms, one of the earliest and most common signs of the disorder is a “floppy” baby appearance, with weak muscle tone (hypotonia). Beginning in childhood (around 3-8 years of age), children with PWS will develop an insatiable, uncontrollable appetite that can cause life-threatening obesity. They may hoard food or lash out if they do not receive food when they’re hungry.
People with PWS tend to be short in stature (if not treated with growth hormone) and might be slow to develop some language, cognitive, and motor skills. They may also have small hands and feet and fair, light-colored skin.
What’s more, people with PWS may have distinctive facial features including:
- A triangular mouth
- Narrow forehead
- Narrow nasal bridge
- Almond-shaped eyes
- Poor eye muscle control (strabismus strabismus A condition in which the eyes don't look in exactly the same direction at the same time. This is also known as “crossed eyes” or eye misalignment. )
How is PWS inherited?
Although all cases of PWS are caused by a change in genetics, most cases are not due to a single gene change that runs in the family. The majority of cases (70%) are caused by the inheritance of a new and random deletion of a piece of the father’s chromosome 15, which plays an important role in regulating appetite. In another 25% of cases, two copies of chromosome 15 are inherited from the mother instead of one copy from both parents. This is referred to as uniparental disomy. In a small number of cases, a rearrangement (translocation) of the genes on a chromosome causes PWS. If PWS is caused by a rearrangement of genes, there is an increased risk for siblings and other family members to be affected by PWS.
How is Prader-Willi syndrome diagnosed?
If Prader-Willi syndrome is suspected, a genetic test on blood called a “DNA methylation” study will detect the syndrome in more than 99% of affected individuals. Other genetic tests may be ordered to detect gene rearrangements if the DNA methylation studies are normal.