What is Prader-Willi Syndrome?

Prader-Willi syndrome (PWS) is a genetic disorder that occurs in approximately one out of every 15,000 births. PWS affects males and females with equal frequency and affects all races and ethnicities. PWS is recognized as a common genetic cause of childhood obesity.

PWS was first described by Swiss doctors Andrea Prader, Alexis Labhart and Heinrich Willi in 1956 based on the clinical characteristics of nine children they had examined. Over the years, the syndrome has been known as Prader-Willi, Prader-Labhart-Willi or Prader-Willi-Fanconi syndrome, with Prader-Willi syndrome being most commonly used today.

With the work of doctors Prader, Labhart, and Willi, a common phenotype was developed based on clinical findings of small hands and feet, abnormal growth and body composition (small stature, very low lean body mass and early onset childhood obesity), hypotonia at birth, insatiable hunger, extreme obesity and mental retardation in many.

In recent years, the syndrome has been genetically characterized as an abnormality on the long arm of chromosome 15. The symptoms have since been refined and the outlook today, with more accurate diagnostic tests, earlier detection, and better interventions, can be quite different.

What are the symptoms of Prader-Willi syndrome?

The symptoms of Prader-Willi syndrome are caused by dysfunction of a portion of the brain called the hypothalamus. The hypothalamus is a small endocrine organ at the base of the brain that plays a crucial role in many bodily functions, including hunger and satiety, temperature and pain regulation, fluid balance, puberty, emotions, and fertility.

There are two recognized stages of the symptoms associated with PWS:

Stage 1

In the first stage, infants with PWS are hypotonic or "floppy", with very low muscle tone. Weak cry and a poor suck reflex are typical. Babies with PWS usually are unable to breastfeed and frequently require tube feeding. These infants may suffer from "failure to thrive" if feeding difficulties are not carefully monitored and treated. As these children grow older, strength and muscle tone generally improve. Motor milestones are achieved, but are usually delayed.

Stage 2

An unregulated appetite characterizes the second stage of PWS. This stage most commonly begins between ages 2 and 6 years old. Individuals with PWS lack normal hunger and satiety cues. They usually are not able to control their food intake and will overeat if not closely monitored. Food seeking behaviors are very common. In addition, the metabolic rate of persons with PWS is lower than normal. Left untreated, the combination of these problems will lead to morbid obesity and its many complications.

In addition to obesity, a variety of other symptoms can be associated with Prader-Willi syndrome. Individuals usually exhibit cognitive challenges with measured IQs ranging from low normal to moderate mental retardation. Those with normal IQs usually exhibit learning disabilities. Other issues may include speech apraxia/dyspraxia, short stature, small hands and feet, scoliosis, sleep disturbances with excessive daytime sleepiness, undescended testicles in males, skin picking behavior, high pain threshold, and sterility. Behavioral difficulties may include obsessive-compulsive disorder and difficulty controlling emotions. PWS is a spectrum disorder and symptoms vary in severity and occurrence among individuals.

What causes Prader-Willi syndrome?

PWS is caused by a lack of active genetic material in a particular region of chromosome 15 (15q11-q13). Normally, individuals inherit one copy of chromosome 15 from their mother and one from their father. In PWS, the genetic defect causing inactivity of chromosome 15 can occur in one of three ways:

PWS by Deletion

Most often, part of the chromosome 15 that was inherited from the person's father is missing, or deleted, in this critical region. This small deletion occurs in approximately 70% of cases and usually is not detectable with routine genetic analysis such as amniocentesis.

PWS by UPD

Another 30% or so of cases occur when an individual inherits two chromosome 15's from their mother, and none from the father. This scenario is termed uniparental disomy (UPD).

PWS by Imprinting Mutation

Finally, in a very small percentage of cases, a small genetic mutation in the Prader-Willi region causes the genetic material in that area to be inactive.

Is there a cure for Prader-Willi syndrome?

Currently there is no cure for Prader-Willi syndrome, and most research to date has been targeted toward specific treatments. For many individuals who are affected by the disorder, the elimination of some of the most difficult aspects of the syndrome, such as the insatiable appetite and obesity, would constitute a cure in most cases. The Foundation for Prader-Willi Research is interested in advancing research toward treating specific aspects of the syndrome as well as development of a cure for PWS.

You can change the future for children with Prader-Willi syndrome!
Join the Foundation for Prader-Willi Research (FPWR) and see how a dedicated group of caring individuals can make a difference. The FPWR, started by parents of children with PWS, is making a huge difference in the lives of children with Prader-Willi syndrome. Daily, more people join the FPWR and help further this cause. Go here to read more about the FPWR.

Still have more questions? Keep reading below or visit the links on the left that provide additional information on Prader-Willi syndrome.

Is Prader-Willi syndrome hereditary?

Deletion and UPD are random occurrences and generally are not associated with an increased risk of reoccurrence in future pregnancies. In the case of an imprinting mutation, Prader-Willi syndrome can recur within a family.

How do these genetic defects cause the symptoms seen in Prader-Willi syndrome?

At this time, the mechanism by which the nonfunctioning genetic material on chromosome 15 affects the function of the hypothalamus is unknown.

I don't understand a lot about genetics. Where can I learn more?

There is a host of information on the Internet about Prader-Willi syndrome. One of the best places to start in developing a better understanding of the syndrome is to investigate the genetics.

The Genetics Home Reference is a US National Library of Medicine sponsored site with a vast array of information to help understand genetics and genetic conditions. In addition, they have a home reference guide specifically for Prader-Willi syndrome.

Gene Reviews, targeted at health professionals, contains detailed descriptions of diagnosis and management of Prader-Willi syndrome.

One of the largest sources of information regarding research can be found on PubMed . This is an up-to-date, searchable database of more than 16 million research abstracts, with links to articles in the medical literature. Current research on PWS can be found by searching with the relevant terms of (prader willi, PWS, growth hormone, etc.)

PubMed is updated frequently, and the abstracts are not always understandable by the lay person. The FPWR monitors the PWS research activity very closely, and our very own Theresa Strong, Ph.D. is quick to sift through these abstracts and discuss and explain the most relevant of these in her Research Blog . If you want to stay in close touch with the latest research, you might find it better to subscribe to an RSS feed of Theresa's postings.

There are also some government efforts toward research on rare diseases. The Office of Rare Diseases at the National Institute of Health has established a research consortium , headed by Dr. Art Beaudet, to study Angelman, Rett, and Prader-Willi syndromes. The consortium is looking for help by signing up for their contact registry and agreeing to participate in relevant studies of PWS.

The National Human Genome Research Institute at the National Institutes of Health (NIH) has excellent resources on genetics and can help educate those who are interested on the unique aspects of PWS research. One of the unique features of the site is a talking genetics glossary. In addition, the Department of Energy co-sponsors the Human Genome Project, and they have a general resource for genetics education regarding the human genome.

Finally, Cold Spring Harbor Labs has an excellent resource called DNA from the Beginning for learning about genetics.

Note that Prader-Willi syndrome is sometimes misspelled as "Prada Willi" syndrome, "Prader Labhart Willy" or "Prader Willy" syndrome.