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Prader-Willi syndrome


Other Names for this Disease
  • Obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet
  • Prader Labhart Willi syndrome
  • PWS
  • Willi-Prader syndrome
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Overview



What is Prader-Willi syndrome?

What are the signs and symptoms of Prader-Willi syndrome?

What causes Prader-Willi syndrome?

How is Prader-Willi syndrome inherited?

How might Prader-Willi syndrome be diagnosed?

How might Prader-Willi syndrome be treated?


What is Prader-Willi syndrome?

Prader-Willi syndrome (PWS) is a complex genetic condition that affects many parts of the body.[1] At birth, babies with PWS have poor muscle tone and a weak cry. Initially, they are slow feeders and appear undernourished. The feeding problems improve after infancy and often between 2 to 4 years of age, children with PWS become very focused on food and have difficulty controlling their appetite. The overeating often results in rapid weight gain and obesity. Individuals with PWS also often have developmental delays and less-than-average adult height. PSW is caused by missing or non-working genes on chromosome 15. Most cases are not inherited, but occur randomly.[2][3]
Last updated: 4/1/2011

What are the signs and symptoms of Prader-Willi syndrome?

Prader-Willi syndrome is considered a spectrum disorder, meaning not all symptoms will occur in everyone affected and the symptoms may range from mild to severe. There are generally two stages of symptoms for people with Prader-Willi syndrome [4]:

  • Stage 1 -- As newborns with Prader-Willi can have low muscle tone, which can affect their ability to suck properly. As a result, these babies may need special feeding techniques to help them eat. Infants may also have problems gaining weight. As these babies grow older, their strength and muscle tone usually get better. They meet motor milestones, but are usually slower in doing so.

  • Stage 2 -- Between the ages of 1 and 6, the disorder changes to one of constant hunger and food seeking. Most people with Prader-Willi syndrome have an insatiable appetite, meaning they never feel full.  In fact, their brains are telling them they are starving.  They may have trouble regulating their own eating and may need external restrictions on food, including locked kitchen and food storage areas. This problem is made worse because people with Prader-Willi syndrome use fewer calories than those without the syndrome because they have less muscle mass.  The combination of eating massive amounts of food and not burning enough calories can lead to life-threatening obesity if the diet is not kept under strict control.[4]

There are other symptoms that may affect people with Prader-Willi, including [4]:

  • Behavioral problems, usually during transitions and unanticipated changes, such as stubbornness or temper tantrums
  • Delayed motor skills and speech due to low muscle tone 
  • Cognitive problems, ranging from near normal intelligence to mild mental retardation; learning disabilities are common
  • Repetitive thoughts and verbalizations
  • Collecting and hoarding of possessions
  • Picking at skin
  • Low sex hormone levels

Many people with this disorder also have distinctive facial features and short stature. The genitals in both males and females are underdeveloped, and most affected individuals are unable to conceive children (infertile). Additionally, some people with Prader-Willi syndrome have unusually fair skin and light-colored hair.[1]
Last updated: 4/1/2011

What causes Prader-Willi syndrome?

Prader-Willi syndrome is caused by the loss of active genes in a specific region of chromosome 15.[1][2][4] People normally inherit one copy of this chromosome from each parent. Some genes are only active on the copy that is inherited from a person's father (the paternal copy). This parent-specific gene activation is called genomic imprinting.

About 70 percent of cases of Prader-Willi syndrome occur when the region of the paternal chromosome 15 containing these genes is missing.[1]  In 25 percent of cases, a person with Prader-Willi syndrome has two copies of chromosome 15 inherited from his or her mother (maternal copies) instead of one copy from each parent, which is called maternal uniparental disomy. Rarely, Prader-Willi syndrome is caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect that abnormally inactivates genes on the paternal chromosome 15. Each of these genetic changes results in a loss of gene function in a critical region of chromosome 15.[1]

Researchers are working to identify genes on chromosome 15 that are responsible for the characteristic features of Prader-Willi syndrome. Researchers have determined, however, that a deletion of the OCA2 gene on chromosome 15 is associated with unusually fair skin and light-colored hair in some affected individuals. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.[1]
Last updated: 4/1/2011

How is Prader-Willi syndrome inherited?

Most cases of Prader-Willi syndrome are not inherited. The genetic changes occur as random events during the formation of reproductive cells or in early fetal development. Affected people typically have no history of the disorder in their family.[1]

Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited. For example, it is possible for a genetic defect that abnormally inactivates genes on the paternal chromosome 15 to be passed from one generation to the next.[1]

To learn more about the genetics of Prader-Willi syndrome, you may wish to visit the following link from the Prader-Willi Syndrome Association.
http://www.pwsausa.org/syndrome/Genetics_of_PWS.htm
Last updated: 4/1/2011

How might Prader-Willi syndrome be diagnosed?

Signs of Prader-Willi syndrome may be seen at birth. Newborns with the condition are often small and very floppy. Male infants may have undescended testicles. As the child grows older, laboratory tests may show signs related to morbid obesity, such as abnormal glucose tolerance, above normal level of insulin in the blood, excessive carbon dioxide levels, and failure to respond to luteinizing hormone releasing factor.[2]

Individuals are usually diagnosed through molecular testing, which consists of DNA-based methylation testing to detect abnormal parent-specific imprinting within the Prader-Willi critical region (PWCR) on chromosome 15. This testing determines whether the region is maternally inherited only (the paternally contributed region is absent) and detects more than 99% of affected individuals. Methylation-specific testing is important to confirm the diagnosis of PWS, especially in those who have atypical findings or are too young to show significant features to make a clinical diagnosis.[3] This testing can be coordinated by a genetics professional at a genetics clinic.
Last updated: 4/1/2011

How might Prader-Willi syndrome be treated?

Prader-Willi syndrome cannot be cured. However, early intervention can help people build skills for adapting to the disorder.  Early diagnosis can also help parents learn about the condition and prepare for future challenges.[4]

Exercise and physical activity can help control weight and help with motor skills. Speech therapy may be needed to help with oral skills.[4]

Human growth hormone has been found to be helpful in treating Prader-Willi syndrome.  It can help to increase height, decrease body fat, and increase muscle mass.  However, no medications have yet been found to control appetite in those with Prader-Willi.[4]
Last updated: 4/1/2011

References
  1. Prader-Willi syndrome. Genetics Home Reference (GHR). July 2009; http://ghr.nlm.nih.gov/condition=praderwillisyndrome. Accessed 3/24/2011.
  2. O'Reilly D. Prader-Willi syndrome. MedlinePlus. November 2, 2009; http://www.nlm.nih.gov/medlineplus/ency/article/001605.htm. Accessed 3/24/2011.
  3. Cassidy SB, Schwartz S. Prader-Willi Syndrome. GeneReviews. September 2009; http://www.ncbi.nlm.nih.gov/books/NBK1330/. Accessed 3/24/2011.
  4. Prader-Willi Syndrome. National Institute of Child Health and Human Development (NICHD). March 24, 2010; http://www.nichd.nih.gov/health/topics/Prader_Willi_Syndrome.cfm. Accessed 3/24/2011.