Genetic Disorders: Prader-Willi Syndrome

Genetic disorders are one or more abnormalities in genomes, a genetic disorder is usually apparent at birth. Genetic disorders are usually rare and impact one in several thousands, if not millions. Prader-Willi Syndrome is a genetic disorder that causes obesity, intellectual disability, and shortness in height. PWS was first described by Swiss doctors Andrea Prader, Alexis Labhart, and Heinrich Willi in 1956 based on the clinical characteristics of nine children they examined. PWS is recognized as the most common genetic cause of life-threatening childhood obesity. It is estimated that in one 12,000 to 15,000 people has Prader-Willi syndrome. Although considered as a “rare” disorder, PWS is one of the most common conditions seen in genetic
clinics. In 1956, Swiss doctors Andrea Prader, Alexis Labhart, and Heinrich Willi examined nine children that had Prader-Willi syndrome. The common characteristics defined in the initial report included small hands and feet, abnormal growth and body composition, hypotonia at birth, insatiable hunger, extreme obesity, and intellectual disability. Prader-Willi syndrome results of an abnormality of chromosome 15, and definitive diagnosis is now based on genetic testing. Prader-Willi Syndrome is a genetic disorder usually caused by deletion a part of chromosome 15 passed down by the father.
The most common symptoms of Prader-Willi syndrome are behavior problems intellectual disability, and short stature. Hormonal symptoms include delayed puberty and constant hunger leading to obesity. There is no cure for Prader-Willi syndrome but many patients will benefit from a supervised diet. Some symptoms can be treated with hormone therapy. Most causes of PWS are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal (relating to the mother) uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells or in early embryonic development. This phenomenon is called maternal uniparental disomy. Rarely, Prader-Willi syndrome can also be caused by a chromosomal rearrangement called a translation, or by a mutation or other defect that abnormally turns off genes on the paternal chromosome
15. Prader-Willi syndrome is not sex-linked due to the sex chromosomes. The disorder lies in a region of chromosome 15. With the exception of genes related to sex characteristics, all genes come in pairs. One copy is inherited from the father and mother.If one copy is active, or expressed, then the other copy is also expressed. Paternal genes on chromosome 15 are missing. The child inherited two copies of chromosome 15 from the mother and no chromosome 15 from the father. There is some error or defect in paterna genes on chromosome 15. Some types genes act alone. With certain genes it’s normal for the paternal gene to be expressed and the maternal gene to be silent, or repressed. Chromosome 15 is located at 15q11.2-q13 and has been designated the PWS region. Males have one X and Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated p and a long arm designated q. They are subdivided into many bands that are numbered. Chromosome 15q11.2-q13 refers to bands 11.2-13 on the long arm of chromosome 15. The numbered bands specify the location of the thousands of genes that are present on each chromosome.` Early diagnosis and treatment can improve quality of life for a person with Prader-Willi syndrome.
A team of health professionals will likely work with you to manage the condition. You need good nutrition for infants, human growth hormone treatment, sex hormone treatment, healthy diet, treatment of sleep disturbances, overall development, mental health care, and transition to adult care. Physical therapy can restore muscle strength and function through exercise. Behavior therapy is focused on modifying harmful behaviors associated with psychological distress. A “FISH” (fluorescent in-situ hybridization) test will identify people with Prader-Willi syndrome due to deletion, but will not identify those who have Prader-Willi syndrome by “UPD” (uniparental disomy) or an imprinting error. A Chromosome Microarray test detects most chromosome deletions, even many small “atypical” sizes, and it will also detect many cases of UPD. It doesn’t detect all cases of Prader-Willi syndrome and specifically those with imprinting defects. UPD and imprinting defect testing is a DNA test that usually requires blood from the patient and both parents for accurate interpretation. The risk to the sibs of an affected child of having Prader-Willi syndrome depends on the genetic mechanism that resulted in the absence of expression of the paternally contributed 15q11.2-q13 region. The risk to sibs is typically less that 1% if the affected has a deletion, up to 50%, if the affected child has an
imprinting defect and up to 25% if a parental chromosome translocation is present. It is estimated than one in 12,000 to 15,000 people have Prader-Willi syndrome. Prader-Willi syndrome is the most common genetic cause of obesity that has been identified to date. Prader-Willi syndrome is found in people of both sexes and in all races worldwide. Prader-Willi syndrome can occur in any family. Fewer than 20,00 US cases per year.