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. PWS results from an abnormality of chromosome 15, and definitive diagnosis is based on genetic testing.
The symptoms of Prader‐Willi syndrome are likely due to 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 regulating hunger and satiety, body temperature, pain, 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.
Frequently Asked Questions
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 is the result of an abnormality on chromosome 15. There are three ways that this can happen. In many cases, there is a deletion of critical genes on a portion of the 15th chromosome normally contributed by the father. In most of the remaining cases, the entire chromosome from the father is missing and there are instead, two chromosome 15s from the mother; this is known as uniparental disomy. In a very small percentage of cases (<3%) there is an imprinting mutation on chromosome 15 contributed by the father. The genetic material is present, although inactive.
The symptoms of PWS change over time. At birth and as infants, individuals with PWS have poor muscle tone (hypotonia), are “floppy” and may be considered “failure to thrive”. They often have a weak cry, difficulty sucking from a bottle or latching to breast, and frequently require tube feeding. Muscle tone and strength generally improve with time; however, motor milestones are often delayed. During childhood (and beyond), individuals with PWS lack normal hunger and satiety cues. They often are unable to control their food intake and need close monitoring to prevent overeating. Food seeking behaviors become common but vary in onset and intensity. Coupled with a lower metabolic rate than normal, if left untreated, the combination of problems leads to obesity and obesity-related complications. Individuals with PWS usually have measured IQ scores ranging from low normal to moderate intellectual disability. Those with normal IQs tend to exhibit learning disabilities. Other symptoms may include growth hormone deficiency, small hands and feet, scoliosis, high pain tolerance, speech apraxia/dyspraxia, sleep disturbances and behavioral challenges. PWS is a spectrum disorder and all symptoms vary in severity and occurrence.
PWS is diagnosed using a series of specialized genetic tests. Common chromosome tests such as karyotype do NOT reliably detect genetic changes of PWS. Genetic testing for PWS can be expensive and may require sending blood and saliva samples to specialized laboratories. DNA Methylation Testing is the best initial test for determining PWS. This test detects >99% cases of PWS. It may also be referred to as “Prader-Willi/Angelman DNA methylation Panel”. All three genetic subtypes of PWS will have a positive DNA methylation analysis for PWS. The FISH test can be used to determine if the subtype of PWS is deletion, however, it will not detect the other two subtypes of PWS, therefore it should not be used as the first genetic test. Chromosome Microarray testing can be used to detect chromosome deletions and many cases of uniparental disomy (UPD).
Deletion and uniparental disomy are genetically random occurrences and not hereditary. In the case of an imprinting mutation, PWS can reoccur in families. Families concerned about the risk of PWS should speak to a genetic counselor.
Research continues in an effort to find new and promising treatments to manage symptoms and ensure children and adults with the syndrome high quality of life. However, at this time there is no cure for Prader-Willi syndrome.
Human Growth Hormone (HGH) was approved by the Federal Drug Administration in 2000 for use in patients with PWS. Research indicates that HGH is not only effective in increasing stature, decreasing body fat, increasing stamina and bone mineral density; it has positive effects on development and behavior.
Many individuals with the syndrome participate in a variety of therapies, including physical, occupational, and speech therapies.