Prader-Willi Syndrome Ryan Moore Prader-Willi Syndrome (PWS) is a rare genetic disorder associated with developmental delay, obesity,

and obsessive behavior related to eating. It is the most common genetic cause of life-threatening obesity in children. In 1887, Langdon-Down described the first girl with probable PWS during adolescence manifest by mental impairment, short stature, hypogonadism, and obesity, and he termed the condition polysarcia. Seventy years later, Prader and colleagues reported a series of patients with similar phenotypes. In 1981, Ledbetter, identified microdeletions within chromosome 15 as the site for PWS. Prader-Willi syndrome is caused by absence of expression of the paternally active genes on the long arm of chromosome 15, due to deletions from the paternal chromosome, maternal disomy. The absence of the paternally active genes in the "Prader-Willi syndrome-critical" region of Chromosome 15q11.2-13 creates a dependence of the phenotype on the gender of the parent of origin. Symptoms may include: Almond-shaped eyes, Delayed motor development, Floppy newborn infant, Insatiable appetite, food craving, Irregular areas of skin that look like bands, stripes, or lines, Narrow bi-frontal skull, Rapid weight gain, Skeletal abnormalities, Slow mental development, small, Undecended testicles in the male infant, very small hands and feet in comparison to body. People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper outbursts, stubbornness, and compulsive behavior such as picking at the skin. Many affected individuals also have sleep abnormalities. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children. Affected children have an intense craving for food and will do almost anything to get it. This results in uncontrollable weight gain and morbid obesity. Morbid obesity may lead to lung failure with low blood oxygen levels, right-sided heart failure, and death. Behavioral problems and learning difficulties are commonly seen in PWS. Young children manifest temper tantrums, stubbornness, and obsessive-compulsive behaviors that can impede school performance. Some of these behaviors are similar to those found in pervasive developmental disorder (autism); in one study, autistic-like behaviors were found in 19 percent of individuals with PWS (genetics home reference). Other studies suggest that these behaviors are particularly common in PWS caused by uniparental disomy. A variety of psychiatric

symptoms and disorders have been reported among adults including mood disorders and florid psychotic states. A mild to moderate degree of cognitive impairment is a commonly associated characteristic; in one study the mean IQ of individuals with PWS was 40 points below the population average. Food-seeking behaviors may include eating garbage, eating frozen food, and stealing resources to obtain food. Decreased ability to vomit and increased tolerance of pain can promote binging on spoiled foods and delay treatment for gastrointestinal disease. After episodes of binge eating, both thin and obese individuals with PWS have developed abdominal discomfort with acute gastric dilation seen on radiography. Choking episodes, typically associated with voracious eating habits, have been reported as the cause of death among 8 percent of patients in one series of sudden death cases. A variety of gastrointestinal peptides including pancreatic polypeptide, cholecystokinin and ghrelin have been studied among individuals with PWS. The mechanism that causes impaired satiety in individuals with PWS is unknown. However, levels of ghrelin, an orexigenic peptide, are persistently elevated in individuals with PWS as compared to weight-matched controls, providing a possible mechanism for the increased appetite in these patients. Because this does not appear to be the case for young lean patients with PWS, some authors have proposed that a surge in ghrelin might precede the hyperphagia and obesity observed in older children. Brain-derived neurotropic factor (BDNF) is another potential mediator of hyperphagia in PWS; this neurohormone is decreased among individuals with PWS. The diagnosis of PWS is suspected in patients who have characteristic clinical features and is confirmed by genetic testing. Clinical diagnostic criteria were developed in 1993. However, now that definitive testing is available, it is appropriate to use less rigid clinical criteria to determine who should undergo genetic testing. The risk of PWS in siblings of an affected child depends on the type of molecular defect causing PWS in that individual. Thus, genetic testing is important not only to establish the diagnosis of PWS, but to determine the risk of recurrence in future pregnancies. Prader-Willi-Labhart Syndrome (PWS) is the most common syndromic form of obesity and affects between 350,000 and 400,000 individuals worldwide. Both sexes are affected equally. Although prevalence estimates differ among studies, this is likely due to using different methods for case identification, and there is no strong evidence for increased risk in specific

countries or gene pools. Within the United States, the rate of prevalence has been reported between 1 in 16,062 to 1 in 25,000. PraderWilli syndrome has no cure; however, several treatments are in place to lessen the condition's symptoms. During infancy, subjects should undergo therapies to improve muscle tone. Speech and occupational therapy are also indicated. During the school years, children benefit from a highly structured learning environment as well as extra help. Prescription of daily recombinant growth hormone injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.

Works Cited: 1)"Prader-Willi S yndrome." Genetics Home Reference. US National Library of Medicine, 11 14 2011. Web. 15 Nov 2011. < h t t p : / / g h r . n l m . n i h . g o v / c o n d i t i o n / p r a d e r - w i l l i - s yn d r o m e > .

2) K a n e s h i r o , N e i l . " P r a d e r - W i l l i S yn d r o m e . " Y a h o o H e a l t h . A D A M , 0 2 1 1 2 0 0 9 . W e b . 1 5 N o v 2 0 1 1 . < h t t p : / / h e a l t h . ya h o o . n e t / a d a m c o n t e n t / p r a d e r w i l l i - s yn d r o m e / 2 > .