Prader-Willi syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 28, 2016
StartDiseasesPrader-Willi syndrome

Prader-Willi syndrome is a genetic disorder that causes an insatiable appetite (polyphagia or hyperphagia), chronic overeating, obesity, short stature, and intellectual disability. The disorder is the leading cause of life-threatening obesity among children and it can cause severe behavioral problems.


Definition & Facts

Prader-Willi syndrome (PWS) is a disorder caused by the disruption of genes on chromosome 15 passed down by the father. People with PWS never feel full which leads to chronic overeating and a range of health consequences. The condition also leads to weakened muscle tone, developmental delays, and poor growth.

Most people with Prader-Willi syndrome have mild to moderate intellectual disability and behavioral problems such as compulsive behavior and temper problems. There is no cure for Prader-Willi Syndrome, which occurs in about 1 out of every 15,000 births and affects females and males equally. There are a few treatment options that may help with some symptoms of the disorder, including hormone replacement therapy.

Symptoms & Complaints

Prader-Willi is a genetic disorder that disrupts function of the brain's hypothalamus, which is responsible for controlling hunger and thirst and releasing hormones that help in sexual development and height.

The symptoms of Prader-Willi are due to this dysfunction in the hypothalamus, but it is still unknown exactly how the genetic disorder causes the dysfunction. The key feature of the disorder is a constant sense of hunger known as hyperphagia that typically begins at the age of 2. People with PWS never feel full and thus want to eat constantly. Most have great difficulty controlling their weight which leads to complications like obesity, high blood pressure, and diabetes mellitus type 2.

Prader-Willi syndrome is the most common genetic cause of potentially life-threatening childhood obesity. The disorder usually causes mild to moderate intellectual impairment as well as behavioral issues, such as poor temper control and stubbornness.

Many people with Prader-Willi syndrome have short height, light skin, a narrow forehead, and small hands and feet. Many are also unable to have children of their own.

The symptoms of PWS usually change over time and there are two broad stages of the disease: early life then childhood and beyond. Infants with PWS have poor muscle tone and may be "floppy" (hypotonia). They typically have a weak cry, poor suckle reflex, and may be unable to fed by breast or fed by the bottle. Many infants with PWS suffer from failure to thrive if their feeding problems are not treated carefully. 


Prader-Willi syndrome is usually not an inherited disorder, especially in people whose disorder is caused by the deletion of paternal chromosome 15, but it is genetic. The disorder occurs randomly as a result of spontaneous genetic mutations occurring while the sperm and eggs are formed or in early embryonic development. The error can occur in one or more genes. The precise genes responsible for Prader-Willi syndrome are unknown, but it is known that the issue occurs in a specific area of chromosome 15.

Except for sex-related genes, all genes come in pairs with one copy each inherited from the mother and father. With most genes, if one copy is considered active or expressed, the other copy is also expressed, but some genes do act alone.

Prader-Willi syndrome occurs because certain paternal genes from the father that should be expressed are missing or defective and are thus not expressed or the child has inherited two copies of chromosome 15 from the mother with no chromosome 15 from the father. About 70% of cases happen when the father's chromosome 15 is partially deleted.

This genetic disorder disrupts normal function of the hypothalamus region of the brain that controls thirst and hunger and releases hormones responsible for sexual development and growth. 

Diagnosis & Tests

Prader-Willi syndrome is usually diagnosed through a genetic blood test that looks for genetic defects specific to the disorder. This test is called a methylation analysis. A FISH (fluorescence in situ hybridization) test can also identify Prader-Willi syndrome by deletion, the most common cause of the disorder.

The methylation analysis test is the most commonly used testing method because it can identify all types of PWS. After this test, additional tests may be ordered to determine the type of PWS. If an imprinting mutation is suspected, blood tests may be conducted on both parents. It may be important to determine the type of PWS as each type has certain risks. For example, people with PWS by uniparental disomy (UPD) may be at a higher risk for mental disorders as they get older. 

Treatment & Therapy

There is no cure for Prader-Willi syndrome, but treatments are available that target the symptoms of the disorder. The two most difficult aspects of the disorder are obesity and the insatiable appetite. Controlling these symptoms can result in a significant improvement in quality of life and the ability to eventually live independently.

Most children and many adults with PWS have growth hormone deficiency and human growth hormone (HGH) therapy has been found to help people with the disorder. HGH therapy can increase height, reduce body fat, increase muscle mass, and improve bone mineral density. Some research also suggests it improves development and behavior.

There are no medications that have been found to regulate appetite in people with PWS which means strict environmental control and constant supervision are currently the only ways to prevent extreme obesity and life-threatening overeating. Some anti-obesity drugs may benefit people with PWS and clinical trials are still being conducted.

Because many people with PWS have sleep disorders, dental problems, and scoliosis, other treatments and therapies are necessary to address these health problems. A wake-promoting drug called modafinil may be used to combat excessive daytime sleepiness. Dental braces and other forms of orthodontic technology may be recommended to address dental problems. A combination of environmental control, medication, and cognitive behavioral therapy (a form of psychotherapy) may be used to address psychiatric and behavioral problems associated with this disorder. 

Prevention & Prophylaxis

There is no cure and no way to prevent Prader-Willi syndrome. The disorder is rarely inherited and parents who have a child with PWS only have a 1% risk of having another child with the condition. People who have PWS may consider genetic counseling to discuss their risk of having children with the disease.