Prader-Willi syndrome

What causes Prader-Willi syndrome?

Prader-Willi syndrome (PWS) is caused by the loss of active genes in a specific region of chromosome 15. People normally inherit one copy of chromosome 15 from each parent. Some genes on chromosome 15 are only active (or "expressed") on the copy that is inherited from a person's father (the paternal copy). When genes are only active if inherited from a specific parent, it is called genomic imprinting.

About 70% of cases of PWS occur when a person is missing specific genes on the long arm of the paternal copy of chromosome 15. This is called a deletion. While there are copies of these same genes on the maternal copy of chromosome 15, the maternal copies of these genes are not expressed.

In about 25% of cases, PWS is due to a person inheriting only 2 maternal copies of chromosome 15, instead of one copy from each parent. This is called maternal uniparental disomy.

Rarely (in about 2% of cases), PWS is caused by a rearrangement of chromosome material called a translocation, or by a change (mutation) or other defect that abnormally inactivates genes on the paternal chromosome 15.

Each of these genetic changes result in a loss of gene function on part of chromosome 15, likely causing the characteristic features of PWS.

Last updated on 05-01-20

How is Prader-Willi syndrome diagnosed?

There are clinical diagnostic criteria for Prader-Willi syndrome (PWS) that were developed in the past that continue to be useful. These criteria can be viewed on the National Institute of Health's NICHD Web site.

However, the current mainstay of a diagnosis when PWS is suspected is a form of genetic testing called DNA methylation testing. This testing can detect abnormal, parent-specific imprinting on the region of chromosome 15 that is responsible for PWS. It determines whether the region is maternally inherited only (i.e., the paternally contributed region is absent) and confirms a diagnosis in more than 99% of affected people. DNA methylation testing is especially important in people who have non-classic features, or are too young to show enough features to make the diagnosis based on signs and symptoms alone.

Last updated on 05-01-20

Is Prader-Willi syndrome inherited?

Most cases of Prader-Willi syndrome (PWS) are not inherited and are due to random events during the formation of egg or sperm cells, or in early fetal development. This is usually the case when PWS is caused by a deletion in the paternal chromosome 15, or by maternal uniparental disomy. However in rare cases, a genetic change responsible for PWS can be inherited.

The risk to family members of a person with PWS depends on the genetic cause of the condition in the affected person. Because the various genetic causes of PWS are complex, people seeking information about specific risks to themselves or family members are encouraged to speak with a genetics professional.

Last updated on 05-01-20

Can the menstrual cycle happen early in people with Prader-Willi syndrome?

Many people with Prader-Willi syndrome (PWS) experience delayed puberty which fails to reach completion. Most females never have regular menstrual cycles, with spontaneous menarche occurring in only about 50% of cases. Even in those who do experience menstruation, the cycles are often just a periodical vaginal spotting. However, a few cases of precocious puberty with menarche at or before age 8 in people with PWS have been reported.

Last updated on 05-01-20

Is puberty altered in people with Prader-Willi syndrome?

People with Prader-Willi syndrome (PWS) typically have hypogonadism, which can manifest as genital hypoplasia (underdevelopment), incomplete pubertal development, and infertility. A small percentage of people with PWS may have early development of pubic hair; more rarely, precocious puberty (abnormally early onset of puberty, before the age of 8) has been reported.

Last updated on 05-01-20

Is prenatal testing available for Prader-Willi syndrome?

Prenatal testing for Prader-Willi syndrome (PWS) is available but should only be considered after genetic testing has confirmed PWS in a family member and the parents have been counseled about the risk to the fetus. Generally, even parents who have had one child with PWS caused either by deletion or uniparental disomy (and who do not have a chromosomal rearrangement) have a low recurrence risk, but may consider prenatal testing for reassurance. When other genetic changes are responsible, the recurrence risk may be much higher (possibly up to 50%).

For "high risk" pregnancies (i.e., families who have a child with PWS), prenatal testing is possible but most of the genetic changes that lead to PWS are not detected by standard prenatal chromosome analysis. While several types of more specific tests have been used in prenatal diagnosis, only DNA methylation analysis of a specific chromosomal location will identify imprinting defects.

Additionally, while prenatal testing of cells obtained by chorionic villus sampling (CVS) or amniocentesis can be done, only a few clinical labs have the experience to use DNA methylation analysis in prenatal diagnosis - and these labs typically prefer to use cells obtained by amniocentesis.

For low-risk pregnancies (i.e. there is no family history of PWS), PWS may be suspected after previous prenatal testing, in which case further testing may be performed.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which an imprinting center deletion has been identified. PGD may also be used when there is a familial translocation, to rule out uniparental disomy.

It is strongly recommended that people with specific questions about prenatal testing for PWS speak with a genetic counselor or other genetics professional.

Last updated on 05-01-20

Is it possible for people with Prader-Willi syndrome to have high IQs?

Most people with Prader-Willi syndrome (PWS) have mild to moderate intellectual impairment and learning disabilities. One study found that people with PWS have a range of IQs with an overall average IQ of 60, which is 40 points lower than in the general population. Some people with PWS have an IQ that is within the average range; there have been reports of affected people with IQs of 103 and 105. However, even with an IQ in the average range, a person with PWS may have a lack of understanding for abstract concepts, and may still experience difficulty relating to peers. We were not able to find any published case reports or studies, however, reporting a person with PWS in the above average range.

Last updated on 05-01-20

My brother has Prader-Willi syndrome. What is the chance my child will have it?

The exact risk to family members of a person with Prader-Willi syndrome (PWS) depends on the genetic cause of the condition in the affected person. Therefore, it is not possible to estimate the exact chance for someone to be affected. Most cases of PWS are not inherited and the recurrence risk is usually low. Familial PWS (occurring in more than one person in a family) is very rare.

People who are concerned about their risk of having a child with PWS should have genetic counseling, which includes a discussion of potential risks to offspring, whether genetic testing is available and appropriate, and reproductive options.

Last updated on 05-01-20

What is the long-term outlook for people with Prader-Willi syndrome?

Children with Prader-Willi syndrome (PWS) can be mainstreamed into the classroom environment, although they need additional speech therapy and should have additional physical activity periods in place of rest periods. They generally need a structured environment and may need a smaller classroom size for individual attention.

People with PWS usually reach adulthood and are able to function in a group home setting, performing vocational work, or attending community college classes. According to the Prader-Willi Syndrome Association, people with PWS can expect to accomplish many of the things their peers do. However, they do need a significant amount of support from their families and from school, work, and residential service providers. Even those with IQs in the normal range need lifelong diet supervision and protection from food availability.

Complications that could affect the quality of life and potentially shorten life expectancy include those relating to hypogonadism, behavioral or psychological issues, and morbid obesity.

Last updated on 05-01-20

How might Prader-Willi syndrome be treated?

A multidisciplinary team approach is ideal for the treatment of people with Prader-Willi syndrome (PWS). Early diagnosis, early multidisciplinary care, and growth hormone treatment have greatly improved the quality of life of many affected children. In general, management of this condition depends on the affected person's age and symptoms.

When a diagnosis of PWS is made, several evaluations are needed to assess the extent of the condition. For example, newborns should be assessed for sucking problems; infants should be assessed for development; and young children should have a vision exam. All males should be evaluated for the presence of cryptorchidism. Other associated conditions for which evaluations may be recommended include hypothyroidism, scoliosis, behavioral problems, psychosis, and respiratory problems and sleep issues.

In infants, special feeding techniques may be needed. Young children often need early intervention, including physical therapy for muscle strength and reaching physical milestones, and speech therapy for language issues. Cryptorchidism may resolve on its own but usually requires hormonal and/or surgical treatment. When excessive eating begins and weight percentiles increase, affected children should be on a program of a well-balanced diet, exercise, and close supervision with food. A consultation with a dietitian is recommended. Behavioral problems may be addressed with special behavioral management programs. Serotonin uptake inhibitors have helped many affected teenagers and adults, particularly those with obsessive-compulsive symptoms.

Growth hormone treatment can normalize height, increase lean body mass, increase mobility, and decrease fat mass. Controlled trials of growth hormone therapies have shown significant benefit from infancy through adulthood. Benefits may include an increase in language and cognitive skills, and better motor performance. Sex hormone replacement helps to produce secondary sex characteristics (those that develop during puberty) but is somewhat controversial due to possible behavior problems in males, risk of stroke, and hygiene concerns related to menstruation in females.

Clinical trials investigating potential treatment options for people with PWS are ongoing. ClinicalTrials.gov provides patients, family members, and members of the public with current information on clinical research studies for PWS. Use each study's contact information to learn more.

Last updated on 05-01-20

Name: Prader-Willi Syndrome Association 8588 Potter Park Drive, Suite 500
Sarasota, FL, 34238, United States
Phone: 941-312-0400 Toll Free: 800-926-4797 Fax : 941-312-0142 Email: national@pwsausa.org Url: http://www.pwsausa.org/
Name: Foundation for Prader-Willi Research 340 Lemon Ave #3620
Walnut, CA, 91789, United States
Toll Free: 888-322-5487 Fax : 888-559-4105 Email: info@fpwr.org Url: http://www.fpwr.org/
Name: International Prader-Willi Syndrome Organisation IPWSO c/o BIRD Europe Foundation Onlus Via Bartolomeo Bizio 1
Costozza 1-36023
Italy
Phone: 39 0444 555557 Fax : 39 0444 555557 Email: g.fornas@alice.it Url: http://www.ipwso.org

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