Uniparental disomy

Definition

Prader-Willi syndrome (PWS) is caused by a rare birth defect centered on chromosome 15. Characteristics of the syndrome include developmental delays and mental retardation, behavioral problems, and insatiable appetite leading to obesity. Affected individuals also experience incomplete sexual development, poor muscle tone, and short stature as adults.

Description

PWS occurs in 1 in 12,000 to 15,000 births and is regarded as the most common genetic cause of obesity. It affects both genders and all races. Although PWS arises from a genetic defect, it is not an inherited condition--it is a birth defect. The defect occurs spontaneously and specifically involves chromosome 15.

A person normally inherits one copy of chromosome 15 from each parent. In PWS cases, the copy from the father either lacks a specific segment of DNA (70-75% of cases) or is missing altogether (25-30% of cases). If the father's chromosome 15 is absent, a person with PWS has two copies of the mother's chromosome 15. Although the individual has the proper number of chromosomes, inheriting two copies of a chromosome from one parent is an abnormal situation called uniparental disomy. If that parent is the mother, it is called maternal uniparental disomy.

Causes & symptoms

Virtually all parents of individuals with PWS have normal chromosomes; fewer than 2% of cases are linked to an inherited genetic mutation. In most cases, an error occurs during embryo development. This error leads to deletion of part of the father's chromosome 15 or to maternal uniparental disomy for chromosome 15. In either case, genes that should have been inherited from the father are missing and PWS develops.

Newborns with PWS have low birth weight, poor muscle tone, are lethargic, do not feed well, and generally fail to thrive. Their genitalia are abnormally small, a condition that persists lifelong. At about two to four years of age, children with PWS develop an uncontrollable, insatiable appetite. Left to their own devices, they will eat themselves to extreme obesity.

Motor development is delayed 1-2 years, and speech and language problems are common. Mild mental retardation is present in about 63% of cases; moderate mental retardation occurs in 31% of cases. Severe mental retardation is seen in the remainder.

Individuals with PWS often develop behavior problems--ranging from stubbornness to temper tantrums--and are easily upset by unexpected changes. Other common characteristics include a high pain threshold, obsessive/compulsive behavior, dental problems, and breathing difficulties. About two-thirds of individuals cannot vomit even after consumption of spoiled food or other noxious substances.

Puberty may occur early or late, but it is usually incomplete. In addition to the effects on sexual development and fertility, individuals do not undergo the normal adolescent growth spurt and are short as adults. Muscles often remain underdeveloped.

Diagnosis

Symptoms can lead to a diagnosis of PWS. This diagnosis can be confirmed through genetic testing.

Treatment

PWS cannot be cured. Treatment involves speech and language therapy and special education. Stringent control of food intake is vital to prevent obesity-related disease and death. A lifelong restricted-calorie diet accompanied by regular exercise is needed to control weight. Unfortunately, diet drugs do not work for individuals with PWS, but medications may be helpful in treating behavioral and psychological problems. Growth and development of secondary sexual characteristics can be achieved with hormone treatment, but decisions regarding such treatment are made on an individual basis.

Prognosis

Life expectancy may be normal if weight can be controlled. Individuals with PWS typically do best in settings that offer a stable routine and restricted access to food.

Prevention

PWS currently cannot be prevented.

Key Terms

Chromosome

A structure composed of DNA contained within a cell's nucleus. The DNA condenses into these readily recognizable structures only at certain times during cell growth. In humans, DNA is bundled into 23 pairs of chromosomes, each of which has recognizable characteristics--such as length and staining patterns--that allow individual chromosomes to be identified. Identification is assigned by number (1-22) or letter (X or Y).

DNA

Abbreviation for deoxyribonucleic acid, the material that composes genes.

Gene

A DNA sequence that carries the blueprint for a specific product, such as a protein.

Genetic testing

A laboratory procedure that can detect the presence of a gene and possibly whether it has abnormalities.

Hormone treatment

Therapeutic administration of a hormone-- such as growth hormone or a sex hormone--to overcome a deficiency or lack of the hormone in the body.

Mutation

A change in a gene that alters the function or other characteristics of the gene's product.

Uniparental disomy

An unusual condition in which an individual inherits two copies of the same chromosome from one parent rather than one copy from each parent.

Further Reading

For Your Information

Books

• Jones, Kenneth Lyons. "Prader-Willi Syndrome." In Smith's Recognizable Patterns of Human Malformation. 5th edition. Philadelphia: W.B. Saunders, 1997.

  Periodicals

• Cassidy, Suzanne B. "Prader-Willi Syndrome." Journal of Medical Genetics 34 (1997): 917-923.

  Organizations

• The Prader-Willi Foundation. 223 Main Street, Port Washington, NY 11050. (800) 253- 7993. http://www.prader-willi.org/
• Prader-Willi Syndrome Association (USA). 5700 Midnight Pass Rd., Sarasota, FL (800) 926-4797 or (941) 312-0400. http://www.pwsusa.org/

  Other

• The Prader-Willi Connection. Owned and operated by Prader-Willi Perspectives, a division of Visible Ink Incorporated, 40 Holly Ln., Roslyn Heights, NY 11577 http://www.pwsyndrome.com/

Gale Encyclopedia of Medicine. Gale Research, 1999.