Prader-Willi+Syndrome

toc = = =Prader-Willi Syndrome (PWS)= By Alex Haigh

What is Prader-Willi?
PWS is a genetic disorder of the 15th Chromosome, on the q12 band, more specifically. 1 in 12,000 to 1 in 15,000 people have the disorder, and it is equally likely to happen in people of all races and genders. The main symptoms include low muscle tone (hypotonia), infertile sex organs (hypogonadism), excessive ingestion of food (hyperphagia), learning disabilities or some level of mental retardation (cognitive impairment) and temper issues. If ingestion of food is not controlled, then the disorder may lead to severe obesity or even death. (//Websites 1, 2, 3)//

Causes of Prader-Willi Syndrome
There are 3 main causes of PWS-- Deletion, UPD (Maternal Disomy), and an Imprinting Defect. //(Website 2)//

Deletion
Deletion is the cause of 70% of all cases of PWS, and involves more than one gene. It occurs when the q12 band of the 15th chromosome inherited from the father is deleted. Because of //Genetic Imprinting//, the mother's gene's from the q12 band are turned "off", and the only on genes are in the father's q12 band. Some of the genes on the q12 band are required for normal development, and since there is no q12 band that is on, the child develops abnormally. When the q12 band on the mother's 15th chromosome is deleted, the result is Angelman's Syndrome (AS), which is a completely different disorder. (//Websites 2, 3, 4)//

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UPD (Maternal Disomy)
UPD, or Maternal Disomy, occurs in about 25% of people with PWS. UPD is when both of the 15th chromosomes are from the mother. Since the maternal q12 bands are turned off, the child has no q12 band that is turned on, which is required for normal development. //(Websites 2, 3, 4)// // (Image 1)//

Imprinting Defect
Imprinting defects are the source of 5% of PWS cases. There is an imprinting center in the q12 band, the critical region for PWS. If there is a micro-deletion in the imprinting center on the paternal 15th Chromosome, then parts of the q12 band will not function normally. This also results in PWS. (//Websites 2, 3, 4)//

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//(Image 1)//

Punnett Square
A Punnett Square is a grid that is used to show a cross between two parents to determine the probability of an offspring having a specific trait. PWS is a dominant trait, which means that if a person has any of the three mutations mentioned above, they have the disorder. If PWS was recessive, people would need two of the mutations to happen, which is impossible. However, almost all people who have PWS are infertile, so there is no way to show PWS inheritance on a pedigree or Punnett Square. //(Websites 1, 2)//

The First Stage of PWS-- The Early Years
When a child with PWS is a baby, they have trouble growing and gaining weight; they are failing to thrive. Because of their hypotonia infants with PWS can't drink from a bottle and require special feeding techniques. Sometime between the ages of 1 and 4, the child develops an obsession with food due to a problem with the Hypothalamus, causing it to not function properly. //(Websites 3, 5)//

Appetite Disorders
When a child with PWS becomes obsessed with food, it is impossible to stop their hunger. As mentioned, there is an issue with the Hypothalamus, which is the part of your brain which controls hunger and thirst and also releases hormones that induce the release of substances for sexual development and growth. The Hypothalamus does not function properly, resulting in a lack of ability to realize that they're full. You know that overstuffed, fat feeling that you have after Thanksgiving Dinner? If somebody has PWS, they would feel just as they did before the meal. They will clean out the entire refrigerator and cabinets if they aren't locked, and will eat themselves to death if eating is not strictly monitored. One of the hardest parts of dealing with PWS is that people with the disorder need only 1,000 kcal per day because of their low muscle mass, but they eat more than a normal person. (//Websites 1, 6)//

The Hypothalamus
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Jessica
media type="youtube" key="cNATWsVVwgo" height="344" width="425" //(Youtube Video 1)//

The Diet of a Person With PWS
This is the typical controlled diet of a person at Gretton Homes, a center for PWS patients.  Breakfast: Bran cereal and one slice of wholemeal toast Lunch: Prawn salad pitta bread. A low fat yogurt and apple for desert Tea: Vegetable curry with boiled rice and broccoli. Low fat mousse for desert Supper: Low fat hot chocolate and two plain biscuits. //(Website 7)//

Mental Development
People with PWS generally have some form of mental retardation. Their IQ is typically around 70, ranging from 40 to 105. The average IQ in the general population is 100. Even if they have a normal IQ, a person will almost always have some form of learning disabilities. For PWS patients, special education services should be addressed in preschool. They lack skills such as attention span, auditory memory and abstract thinking. They do, however, sometimes have strengths in long-term memory. //(Website 1)//

Motor Skills
Motor skills development is generally delayed by 1-2 years. Despite the fact that their muscle tone improves, PWS patients still have a lack of balance and coordination. Physical Therapy is recommended for all patients. Part of how Jessica (the child in the video above) lost her weight was by going to Physical Therapy 5 times a week. //(Website 1)//

Life Changes
People with the PWS need constant treatment and care for their entire lives. They need to work out every day, and need their food consumption strictly monitored. In most cases, the kitchen cabinets and fridge are locked, so the people with PWS can't get to the food. There are special homes for adults of all ages with PWS where they can stay, such as Gretton Homes in England. Infants with PWS need special feeding techniques, and some children need speech therapy. All children with PWS should do Physical Therapy. Most of the time, children with PWS can't go to public school, and if they do, they get a lot of extra help because of their learning disabilities. //(Website 1, 5)//

Discovery, Treatments, and Research
PWS was discovered in 1956 by 3 Swiss doctors: Prader, Labhart, and Willi, thus the name Prader-Willi Syndrome. Sadly, there is no treatment for PWS. There is a medicine called Rimonabant, which is supposed to control appetite; however, it is not approved by the FDA in the US. Despite popular support, it hasn't been rigorously tested, so there is no way to tell its effects on PWS patients. Human Growth Hormone (HGH) is sometimes used to help deal with Hypotonia. The largest PWS research foundations are the Prader-Willi Syndrome Association USA (PWSAUSA) and the Foundation for Prader-Willi Research (FPWR). There haven't been any recent medical breakthroughs in PWS since 1989. //(Websites 1, 6, 7)//

media type="youtube" key="Vr5nSFf2p2Y" height="344" width="425" //(Youtube Video 2)// Even Famous people like Rockies' Manager, Clint Hurdle get involved in supporting PWS

**Genetic Testing**
There are two primary tests used to detect PWS: FISH and High Resolution Chromosomal Analysis, which is similar to a Karyotype. Both are used, often at the same time. FISH detects typical deletions, but can't pick UPD, the cause of 25% of all cases. High Resolution Chromosomal Analysis detects all major deletions and extra chromosomes, but can't pick up small deletions or UPD. As you can see, neither test can pick up UPD, a cause of PWS. Because of this, PWS goes highly under diagnosed. //(Website 4)// 