Prader-Willi syndrome (PWS) is a variable and complex genetic neurobehavioral disorder resulting from abnormality on the 15th chromosome. It occurs in males and females equally and in all races. Prevalence estimates range from 1:15,000 to 1:25,000.

PWS is felt to be a multistage disorder with decreased fetal movement prenatally and low birth weight. Infants have failure to thrive due to feeding problems and hypotonia. Toddlers have increased weight gain, then hyperphagia and obesity as they get older, if calories are not restricted. Most of the medical problems in Prader-Willi syndrome are related to obesity, hypotonia, and hypothalamic dysfunction. Other factors that may include adverse reactions to medications, high pain tolerance, gastrointestinal and respiratory issues, lack of vomiting, and unstable temperature. Adrenal insufficiency may also occur. The most common and challenging symptom among those diagnosed is hyperphagia, insatiable hunger, and can lead to life-threatening 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.

PWS is a spectrum disorder with symptoms varying in difficulty per individual. PWS affects the functioning of the hypothalamus and other aspects of the brain, and typically causes the following frequent findings:

• Generalized hypotonia
• Decreased ability to suck in infancy leading to failure to thrive if not compensated
• Swallowing abnormalities of oral secretions and food in all ages, often unrecognized
• Hyperphagia due to hypothalamically-driven lack of sense of satiety that can lead to dramatically excessive eating and coupled with body composition abnormalities and metabolism with low caloric needs, can result in morbid obesity. Hyperphagia begins as early as 2-4 years and lasts throughout life.  Those with PWS who are not obese have had food intake carefully controlled by others
• Short stature for the family if not treated with growth hormone
• Hip dysplasia, scoliosis, osteoporosis
• Delayed and incomplete sexual development
• Developmental delay and usually mild to moderate learning/cognitive deficits
• Chronic and significant problem behavior
• Adverse reactions to medications
• High pain tolerance leading to unsuspected issues such as fractures
• Gastrointestinal issues including decreased ability to vomit and chronic constipation. Occasional stomach necrosis and rupture often following binge eating
• Respiratory abnormalities including sleep disordered breathing in the form of obstructive or central sleep apnea
• Temperature regulation abnormalities (hypothermia or hyperthermia)

More information and resources may be found in our Medical A-Z section of our website or by calling PWSA | USA directly at (941) 312-0400.

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).  

Those diagnosed with PWS typically have no history of the disorder in their family.  PWS is caused by lack of expression of a group of genes on the proximal long arm of chromosome 15 (15q11.2-q13).  There are primarily three subtypes:

1. Deletion - In about 2/3 of cases, this expression deficiency is due to absence (deletion) of a segment of the chromosome 15 contributed to the affected individual by the father.
2. Uniparental Disomy (UPD) – is due to the presence of two maternally-contributed and no paternally-contribute chromosome 15
3. Imprinting Defect – this is the least common cause and is a defect in the imprinting center such that both parental copies of the relevant genes in the PWS region of chromosome 15 are suppressed

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.