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 the most common genetic cause of life-threatening 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 examined. The common characteristics defined in the initial report included small hands and feet, abnormal growth and body composition (small stature, very low lean body mass, and early-onset childhood obesity), hypotonia (weak muscles) at birth, insatiable hunger, extreme obesity, and intellectual disability.
In recent years, the syndrome has been characterized genetically as an abnormality of chromosome 15, and definitive diagnosis is now based on genetic testing.
Currently, there is no cure for Prader-Willi syndrome, and most research to date has been targeted towards treating specific symptoms. For many individuals affected by the disorder, the elimination of some of the most difficult aspects of the syndrome, such as the insatiable appetite and obesity, would represent a significant improvement in quality of life and the ability to live independently. The Foundation for Prader-Willi Research is interested in advancing research toward understanding and treating specific aspects of the syndrome, with the goal of an eventual cure for PWS.
Deletion and UPD are random occurrences and generally are not associated with an increased risk of recurrence in future pregnancies. In the case of an imprinting mutation, Prader-Willi syndrome can reoccur within a family. Families with concerns about their risk for PWS should speak to a genetic counselor.
The symptoms of Prader-Willi syndrome are thought to be 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, sleep-wake balance, fluid balance, emotions, and fertility. Although hypothalamic dysfunction is believed to lead to the symptoms of PWS, it is not yet clear how the genetic abnormality causes hypothalamic dysfunction.
There are two generally recognized stages of the symptoms associated with PWS:
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.
An unregulated appetite characterizes the second stage of PWS. This stage most commonly begins between ages 2 and 8 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, this combination of problems leads to morbid obesity and its many complications.