Disease name: Prader-Willi syndrome
Affected populations: This genetic, multisystem disorder affects an estimated 1 in 30,000 to 1 in 10,000 people worldwide. Most cases of the syndrome occur sporadically, meaning the genetic changes behind the condition appear randomly in early development rather than being passed down through generations. Only in rare cases is the genetic trigger inherited.
The syndrome affects males and females at equal rates, as well as people of different racial and ethnic backgrounds. Approximately 10,000 to 20,000 people in the United States have Prader-Willi syndrome.
Causes: The syndrome occurs when specific genes on chromosome 15 lose their function, either because they are missing or because they’ve been turned off. The portion of chromosome 15 that’s affected in Prader-Willi syndrome is called 15q11.2-q13, and it’s also known as the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region.
Human cells typically carry 46 chromosomes, including 22 pairs of non-sex chromosomes, numbered 1 through 22, and one pair of sex chromosomes. Each parent contributes one-half of each pair of non-sex chromosomes — so one copy of chromosome 15 comes from the mother and another comes from the father, for example. Because cells carry two copies, every gene on each chromosome does not need to be active. Through a process called “genetic imprinting,” certain genes on either the mother’s or the father’s copy get switched off.
Prader-Willi syndrome affects the paternal copy of chromosome 15, and in most cases — around 60% or 70% — the PWS/AS region is randomly deleted during development. Meanwhile, the maternal PWS/AS region is switched off in everyone. Thus, the deletion leaves people without a working set of those genes.
For about 30% to 40% of people with the syndrome, they inherit two copies of the maternal chromosome 15, so they’re missing the paternal copy altogether.
More rarely, a person carries the paternal chromosome 15 but the relevant genes do not work properly. This happens due to either a small genetic mutation — a “microdeletion” — or changes in epigenetics, which are modifications to DNA that don’t change its code but can turn a gene on or off. Even more rarely, the syndrome may be triggered by translocation, in which a portion of chromosome 15 breaks off and then reattaches to a different chromosome.
Symptoms: Prader-Willi syndrome affects many parts of the body, and its symptoms can vary from person to person. Many of the genetic changes that underlie the syndrome are thought to affect the hypothalamus, a key hormone-making region of the brain that helps control many basic bodily functions, including body temperature, hunger and sleep.
Hypotonia, or low muscle tone, is seen in nearly all infants with the syndrome, making them feel “floppy” when held. There can be signs of this symptom before birth, in that the fetus will not move as much as expected or will end up in unusual positions. After birth, hypotonia can contribute to the baby having a poor sucking reflex, which hinders feeding and weight gain in early life. Developmental delays are also common.
Infants can also have distinctive features, such as almond-shaped eyes; a thin upper lip; a downturned mouth; and a long, narrow head. Many patients have short stature, in part due to growth hormone deficiency. A percentage of people with the syndrome lose a gene called OCA2, which is involved in making pigment in the skin and hair. These individuals have very fair skin and light-colored hair.
Later in childhood, around age 2 to 8, children’s appetite often increases dramatically, and these individuals tend to not feel full after meals. This can subsequently lead to hyperphagia, or excessive eating, which can result in obesity and related complications, such as type 2 diabetes, heart issues and gastrointestinal problems. It’s thought that this voracious drive to eat is triggered by issues with the hormones that normally regulate appetite, as well as by differences in brain areas involved with processing rewarding stimuli (like food).
Additional symptoms of Prader-Willi syndrome include cognitive impairment, ranging from mild to moderate; genital underdevelopment; sleep problems; nearsightedness; and underactive thyroid.
With adequate treatment and support, people with Prader-Willi syndrome can live into their 70s. But complications such as diabetes and heart failure can limit their lifespan if these conditions are not adequately controlled, and they can cause death by a person’s 40s.
Treatments: There is no cure for Prader-Willi syndrome. Treatments vary depending which symptoms a person has, when those symptoms began and how severe they are.
To help patients feed in infancy, doctors may recommend high-calorie formula and special feeding methods, including tube feeding. Replacing missing hormones — with testosterone, estrogen or growth hormone, for example — can help offset symptoms related to low hormone levels. Growth hormone therapy was approved as a Prader-Willi syndrome treatment by the Food and Drug Administration (FDA) in 2000, and it’s been shown to help boost muscle tone and growth while lowering body fat.
Physical, behavioral, occupational and speech therapies can help with motor skills, intellectual disabilities, and speech and language development. Medications might be recommended to help with sleep issues or psychiatric disorders that can be associated with the syndrome, such as psychosis.
The FDA also approved the first-ever treatment for hyperphagia in Prader-Willi syndrome in 2025. It’s approved for patients ages 4 and older. The exact mechanism of this drug is unknown, but it’s thought to help decrease the production of certain hunger-triggering signals from the hypothalamus.
Especially in childhood, patients with Prader-Willi syndrome should be kept on carefully controlled diets and eating schedules, the Mayo Clinic advises. Dietitians can help advise patients and their families on what to include in a healthy diet and whether supplemental vitamins or minerals might be necessary.
This article is for informational purposes only and is not meant to offer medical advice.
