Prader-Willi syndrome


Willi-Prader syndrome
Prader-Labhart-Willi syndrome


Prader-Willi syndrome (PWS) is a genetic condition that affects many parts of the body. Infants with PWS have severe hypotonia (low muscle tone), feeding difficulties, and slow growth. In later infancy or early childhood, affected children typically begin to eat excessively and become obese. Other signs and symptoms often include short stature, hypogonadism, developmental delays, cognitive impairment, and distinctive behavioral characteristics such as temper tantrums, stubbornness, and obsessive-compulsive tendencies. PWS is caused by missing or non-working genes on chromosome 15. Most cases are not inherited and occur randomly. Rarely, a genetic change responsible for PWS can be inherited. Management of PWS generally depends on the affected person's age and symptoms.


Symptoms may include:

  • Almond-shaped eyes
  • Delayed motor development
  • Floppy newborn infant
  • Insatiable appetite, food craving
  • Irregular areas of skin that look like bands, stripes, or lines
  • Narrow bifrontal skull
  • Rapid weight gain
  • Skeletal (limb) abnormalities
  • Slow mental development
  • Small for gestational age
  • Undescended testicles in the male infant
  • Very small hands and feet in comparison to body
  • Affected children have an intense craving for food and will do almost anything to get it. This results in uncontrollable weight gain and morbid obesity. Morbid obesity may lead to lung failure with low blood oxygen levels, right-sided heart failure, and death.


Prader-Willi syndrome (PWS) is caused by the loss of active genes in a specific region of chromosome 15. People normally inherit one copy of chromosome 15 from each parent. Some genes on chromosome 15 are only active (or "expressed") on the copy that is inherited from a person's father (the paternal copy). 

About 70% of cases of PWS occur when a person is missing specific genes on the long arm of the paternal copy of chromosome 15. This is called a deletion. While there are copies of these same genes on the maternal copy of chromosome 15, the maternal copies of these genes are not expressed.
In about 25% of cases, PWS is due to a person inheriting only 2 maternal copies of chromosome 15, instead of one copy from each parent. This is called maternal uniparental disomy.

Rarely (in about 2% of cases), PWS is caused by a rearrangement of chromosome material called a translocation, or by a change (mutation) or other defect that abnormally inactivates genes on the paternal chromosome 15.

Each of these genetic changes result in a loss of gene function on part of chromosome 15, likely causing the characteristic features of PWS.


Defective or missing portions of paternal genes responsible for Prader-Willi syndrome usually occur randomly. This means that in most instances, Prader-Willi syndrome can't be prevented. However, in a small number of cases, a genetic mutation inherited from the father may cause Prader-Willi syndrome.


A suspected diagnosis of Prader-Willi syndrome (PWS) is usually made by a physician based on clinical symptoms. PWS should be suspected in any infant born with significant hypotonia (muscle weakness or “floppiness”). The diagnosis is confirmed by a blood test. The preferred method of testing is a “methylation analysis,” which detects >99% of cases, including all of the major genetic subtypes of PWS (deletion, uniparental disomy, or imprinting mutation). A “FISH” (fluorescent in-situ hybridization) test will identify those patients with PWS due to a deletion, but it will not identify those who have Prader-Willi syndrome by “UPD” (uniparental disomy) or an imprinting error.


Children with Prader-Willi syndrome (PWS) can be mainstreamed into the classroom environment, although they need additional speech therapy and should have additional physical activity periods in place of rest periods. They generally need a structured environment and may need a smaller classroom size for individual attention.

People with PWS usually reach adulthood and are able to function in a group home setting, performing vocational work, or attending community college classes.According to the Prader-Willi Syndrome Association, people with PWS can expect to accomplish many of the things their peers do. However, they do need a significant amount of support from their families and from school, work, and residential service providers. Even those with IQs in the normal range need lifelong diet supervision and protection from food availability.

Complications that could affect the quality of life and potentially shorten life expectancy include those relating to hypogonadism, behavioral or psychological issues, and morbid obesity.


A multidisciplinary team approach is ideal for the treatment of people with Prader-Willi syndrome (PWS). Early diagnosis, early multidisciplinary care, and growth hormone treatment have greatly improved the quality of life of many affected children. In general, management of this condition depends on the affected person's age and symptoms.

When a diagnosis of PWS is made, several evaluations are needed to assess the extent of the condition. For example, newborns should be assessed for sucking problems; infants should be assessed for development; and young children should have a vision exam. All males should be evaluated for the presence of cryptorchidism. Other associated conditions for which evaluations may be recommended include hypothyroidism, scoliosis, behavioral problems, psychosis, and respiratory problems and sleep issues.

In infants, special feeding techniques may be needed. Young children often need early intervention, including physical therapy for muscle strength and reaching physical milestones, and speech therapy for language issues. Cryptorchidism may resolve on its own but usually requires hormonal and/or surgical treatment. When excessive eating begins and weight percentiles increase, affected children should be on a program of a well-balanced diet, exercise, and close supervision with food. A consultation with a dietitian is recommended. Behavioral problems may be addressed with special behavioral management programs. Serotonin uptake inhibitors have helped many affected teenagers and adults, particularly those with obsessive-compulsive symptoms.

Growth hormone treatment can normalize height, increase lean body mass, increase mobility, and decrease fat mass. Controlled trials of growth hormone therapies have shown significant benefit from infancy through adulthood. Benefits may include an increase in language and cognitive skills, and better motor performance. Sex hormone replacement helps to produce secondary sex characteristics (those that develop during puberty) but is somewhat controversial due to possible behavior problems in males, risk of stroke, and hygiene concerns related to menstruation in females.

Approved treatments:

  • Somatropin [rDNA] (Genotropin) FDA-approved indication: Long-term treatment of pediatric patients who have growth failure due to Prader-Willi syndrome (PWS). 
  • Recombinant human luteinizing hormone (Luveris(injection)) FDA-approved indication: Luveris (lutropin alfa for injection), concomitantly administered with Gonal-f (follitropin alfa for injection), is indicated for stimulation of follicular development in infertile hypogonadotropic hypogonadal women with profound LH deficiency (LH (less than) 1.2 IU/L). 


Refer to Research Publications.