Key takeaways
- Prader-Willi syndrome is a genetic disorder caused by irregularities on chromosome 15. It impacts roughly 1 in 10,000 to 1 in 30,000 individuals worldwide, affecting males and females equally.
- Symptoms evolve across distinct life stages, beginning with low muscle tone and feeding challenges in infancy, then progressing to insatiable hunger that typically emerges around age 2 and persists throughout life.
- While no cure exists, lifelong specialized care combining growth hormone therapy, strict nutritional management, and behavioral support can significantly improve outcomes and help individuals maintain a healthy weight.
Prader-Willi syndrome (PWS) is a rare condition that causes physical, mental, and behavioral difficulties.
People with Prader-Willi syndrome have extreme difficulty controlling their body weight due to a powerful compulsion to eat as much food as possible, and it is the most common genetic cause of morbid obesity in children.
The condition requires careful management from infancy through adulthood to ensure the best possible outcomes.
According to the Prader-Willi Syndrome Association (PWSA) in the United States, between 1 in 15,000 and 1 in 25,000 people live with the condition. Other sources suggest the syndrome occurs in between 1 in 10,000 and 1 in 30,000 people globally. It affects both sexes equally.
PWS is a genetic condition, which means that people inherit it from their parents. It is present from birth, although diagnosis may not be immediate.
People with PWS have seven genes on chromosome 15 that are either deleted or inactive. They will often have low muscle tone, incomplete sexual development, and chronic hunger.
Their metabolism tends to burn fewer calories than that of people without the condition. Many individuals with PWS have short stature.
A newborn with PWS tends to have a lower-than-usual birth weight, weak muscles (hypotonia), and difficulties with sucking to feed.
Individuals develop a strong appetite (hyperphagia) from age 2 years, but the average onset age is at age 8 years. However, it can sometimes occur much later, in the teenage years. This is characterized by a significantly reduced feeling of fullness after eating, and once hyperphagia begins, it tends to be lifelong.
Symptoms of PWS typically develop in two stages.
The first symptoms often emerge during the first year of life, and others begin between the ages of 1 and 6 years.
Prader-Willi symptoms in the first year
Between 0 and 12 months of age, an infant is likely to have some or all of the following symptoms:
- Low muscle tone, also known as hypotonia: The infant feels floppy when held by another person. The elbows and knees may be loosely extended rather than firmly in place. Hypotonia often improves with age.
- Specific facial features: These may include almond-shaped eyes and a head that narrows at the temples. The mouth may appear small and downturned, with a thin upper lip.
- Reduced physical development: Poor muscle tone can impair sucking, making feeding difficult. An infant may gain weight at a slower rate than other babies.
- Crossed eye/s (strabismus): The eyes do not move in unison. One eye may appear to wander, or the eyes may cross.
- Underdeveloped genitals: Genitals may not develop correctly.
An infant may also have an unusually weak cry, display incomplete responses to stimulation, and appear tired.
Prader-Willi symptoms from age 1 to 6 years
Toddlers may exhibit the following symptoms:
- Food cravings and gain in body weight: The child craves food constantly, eating large amounts of food with great frequency. They may hoard food or eat items that most people would not, such as frozen food before it is thawed or cooked, or food past its expiry date.
- Hypogonadism: The testes or ovaries do not produce enough sex hormones, resulting in underdeveloped sex organs. The testes of males with PWS may not descend.
- Limited growth and strength: This can include low muscle mass and small hands and feet. People with PWS may not reach their full height as adults due to a lack of growth hormone.
- Limited cognitive development: This might lead to mild to moderate learning disabilities.
- Delayed motor skills: Children might reach common milestones in learning coordination skills, such as sitting up or walking, later than usual.
- Delayed verbal skills: A child with PWS may develop their speech capabilities later.
- Behavioral and psychiatric disorders: These may include temper tantrums, especially around food. A child may be argumentative, oppositional, rigid, manipulative, possessive, and stubborn. Some children may have obsessive-compulsive disorder (OCD), repetitive behaviors, recurring thoughts, and other conditions affecting mental health. They may also experience excessive skin-picking and nail-biting.
- Sleep disorders: These may include sleep apnea, possibly due to obesity. There may be disturbances of the usual sleep cycle.
- Curvature of the spine (scoliosis): This symptom can occur as a child with PWS grows.
- Depigmentation: The skin and hair may be fairer than those of parents and siblings.
- High tolerance for pain: Feeling pain is the body’s natural response to environmental or other forms of discomfort. Those with a high pain tolerance may not feel some sensations as strongly as others, which can be helpful, but can also be a risk through not recognizing dangers soon enough. It may result in injuries, such as unexplained bruising.
- Vision and ocular symptoms: This may include nearsightedness (myopia) or misaligned eyes (strabismus).
The Prader-Willi Syndrome Association is now increasingly seeing PWS as a syndrome of multiple stages rather than just the two used initially.
Going forward, people with PWS undergo inadequate sexual development during puberty. Females may experience scant menstruation or none at all, and most adults with PWS may not be able to reproduce.
Doctors typically diagnose PWS early, but parents should consult a doctor if they notice their:
- baby has difficulty feeding
- baby has difficulty waking up
- baby lacks a response to typical stimulation
- baby displays floppiness when held
- child is constantly seeking food
- child is rapidly weight gain
Other warning signs include constant hunger and persistent food-seeking behavior. There will almost always be other signs, though, and most children who exhibit these behaviors do not have PWS.
Genetic anomalies cause PWS. Researchers have identified irregularities on chromosome 15 that can occur in three ways. Firstly, gene deletion. This is the most common cause, in which essential genes on part of the father’s chromosome 15 are missing.
Secondly, uniparental disomy. This occurs when a child has two copies of chromosome 15 from the mother, rather than one from each parent.
Lastly, imprinting mutation: This means that there is an imprint of the father’s chromosome 15, but it remains inactive. An imprinting mutation occurs in fewer than 3% of PWS cases.
This genetic anomaly changes how the hypothalamus works. The hypothalamus is a part of the brain that controls thirst and hunger. It also releases hormones that promote sexual development and growth.
If the hypothalamus is damaged, for example, through a head injury, tumor, or tumor-removal surgery, PWS-like signs and symptoms may develop.
Despite not having the genetic features of PWS, a person with a damaged hypothalamus may acquire some of the same behavioral challenges, such as constant food cravings, so it is important to discuss all symptoms with a healthcare professional so they can make a clear diagnosis.
A
Early testing is necessary because early diagnosis enables timely treatment.
Some people with PWS do not receive a diagnosis, or they are given a misdiagnosis of Down syndrome or autism spectrum disorder (ASD). This is because some features of these conditions overlap with those of PWS.
There is no cure for PWS. However, ongoing therapies can help reduce symptoms by focusing on related hormone and developmental deficiencies.
Therapies that doctors might use include:
- nutrition
- growth hormone
- sex hormones
- physical
- speech
- occupational
- developmental
Nutrition therapy can provide an infant experiencing feeding difficulties with a high calorie formula.
Doctors treating PWS will closely monitor weight and growth, while a nutritionist may help develop a nutrient-dense, low calorie diet to support weight control.
People with PWS must follow a very strict diet with lower-calorie goals than would be common for the age group. Parents and guardians may need to put physical barriers in place to address food cravings, such as locking food in kitchen cabinets, fridges, and freezers.
Growth hormone treatment can help increase growth and reduce body fat, but the long-term effects of these are unclear.
Sex hormone treatment, such as hormone therapy (HT), can top up testosterone for males and progesterone for females. This helps with sexual development and can reduce the risk of osteoporosis.
Other treatments include:
- developmental therapy to encourage age-appropriate social and interpersonal skills
- occupational therapy to help with routine tasks
- physical therapy to manage coordination and movement
- speech therapy to promote communication ability
A person with PWS may also need to consult a psychologist or psychiatrist for help with the psychological effects of the condition.
Most people with PWS need supervision and specialized care throughout their lives. Continually restricting food and managing behavior can cause stress for family members, but family support and counseling groups can sometimes offer help.
The complications of PWS can include having unusual reactions to medications, especially sedatives and anesthesia.
A person with PWS may have a typically high pain threshold, meaning that an infection or illness does not receive medical attention until its later stages. Vomiting is also rare in people with PWS unless the condition is already severe.
The high prevalence of obesity means a higher risk of type 2 diabetes, heart disease, and stroke than in other people. Similarly, people with PWS have a higher rate of tooth erosion than others.
Osteoarthritis and osteoporosis, affecting the bones and joints, might also occur.
PWS is a condition in which an individual cannot control the urge to eat due to a chromosomal anomaly, as well as delayed growth and slower cognitive development, among other symptoms.
The symptoms often develop in stages, and early identification can help an individual manage the condition.
If a person with PWS can control both obesity and the other complications of the condition, they can expect few, if any, changes to life expectancy.
Q:
Is there a diet to control food cravings in people with PWS?
AnonymousA:
For people with PWS, no specific diet will lessen or control the compulsion to eat. Doctors will often advise restricting calories in the diet of a person with PWS, and such a regimen often requires restricting access to food.
Even before children with PWS develop obesity, they should have a routine of exercise and a controlled intake of food already in place. This helps reduce the severe health consequences of severe overeating that can lead to life threatening obesity.