Prader Willi syndrome

IMPRINTING
Prader-Willi syndrome affects between 1/10,000 and 1/30,000 live births. The study of this disease led to the discovery that, for some genes, the origin of the gene may be important. For some loci the gene inherited from the father acts differently from the gene inherited from the mother, even though they may have the same DNA. This phenomenon is called imprinting. About 75% of patients with Prader-Willi syndrome have a small deletion of the long arm of chromosome 15, a small piece of one chromosome 15 is missing while the homologous chromosome remains intact. When this deletion is on the paternal chromosome (the father's genes are missing) Prader-Willi syndrome results. When this deletion is on the maternal chromosome (the mother's genes are missing) Angelman syndrome results. The two diseases have very different clinical symptoms. The other 25% of Prader-Willi syndrome patients are almost all the result of uniparental disomy, a rare chromosomal event in which both chromosomes come from a single parent. (This will be covered later under chromosomal diseases.) When both chromosomes 15 are derived from the mother, Prader-Willi syndrome results. When both chromosomes 15 are derived from the father, Angelman syndrome results. For normal development an individual must inherit one copy of this chromosomal region from his or her father and one from his or her mother. Several other regions have been found to show uniparental disomy without this effect on the phenotype. Small deletions usually affect the phenotype but they produce the same phenotype whether of maternal or paternal origin. Through some unknown mechanism, the gene, or genes, involved in Prader-Willi and Angelman syndrome know their origin and behave according to that origin. At the present time we do not know whether this is a general phenomenon or not. It might be limited to this small region of chromosome 15. It might be quite wide spread. Imprinting represents an exception to Mendel's laws and remains an important area of research.

PRADER-WILLI SYNDROME

Prader-Willi Syndrome (PWS) is an uncommon genetic disorder. It causes poor muscle tone, low levels of sex hormones and a constant feeling of hunger. The part of the brain that controls feelings of fullness or hunger does not work properly in people with PWS. They overeat, leading to obesity.

There are generally two stages of symptoms for people with Prader-Willi syndrome:
Stage 1--As newborns, babies with Prader-Willi can have low muscle tone, which can affect their ability to suck properly. As a result, babies may need special feeding techniques to help them eat, and infants may have problems gaining weight. As these babies grow older, their strength and muscle tone usually get better. They meet motor milestones, but are usually slower in doing so.
Stage 2--Between the ages of 1 and 6 years old, the disorder changes to one of constant hunger and food seeking. Most people with Prader-Willi syndrome have an insatiable appetite, meaning they never feel full. In fact, their brains are telling them they are starving. They may have trouble regulating their own eating and may need external restrictions on food, including locked kitchen and food storage areas.

This problem is made worse because people with Prader-Willi syndrome use fewer calories than those without the syndrome because they have less muscle mass. The combination of eating massive amounts of food and not burning enough calories can lead to life-threatening obesity if the diet is not kept under strict control.


There are other symptoms that may affect people with Prader-Willi, including:
1. Behavioral problems, usually during transitions and unanticipated changes, such as stubbornness or temper tantrums
2. Delayed motor skills and speech due to low muscle tone
3. Cognitive problems, ranging from near normal intelligence to mild mental retardation; learning disabilities are common
4. Repetitive thoughts and verbalizations
5. Collecting and hoarding of possessions
6. Picking at skin
7. Low sex hormone levels

Prader-Willi syndrome is considered a spectrum disorder, meaning not all symptoms will occur in everyone affected and the symptoms may range from mild to severe.

People with Prader-Willi often have some mental strengths as well, such as skills in jigsaw puzzles. If obesity is prevented, people with the syndrome can live a normal lifespan.


Babies with PWS are usually floppy, with poor muscle tone, and have trouble sucking. Boys may have undescended testicles. Later, other signs appear. These include
Short stature
Poor motor skills
Weight gain
Underdeveloped sex organs
Mild mental retardation and learning disabilities

There is no cure for PWS. Growth hormone and exercise can help build muscle mass and control weight.

Complications :

Obesity-related complications
Many of the possible complications of Prader-Willi syndrome result from obesity. In addition to having constant hunger, people with the disorder have low muscle mass, so they require fewer than average calories. This combination of factors makes a person prone to obesity and the medical problems related to obesity, such as:
• Type 2 diabetes. Type 2 diabetes affects the way your body metabolizes blood sugar (glucose), due to your body's inability to use insulin efficiently. Insulin plays a vital role in making blood sugar (your body's fuel) available to your cells. Obesity significantly increases the risk of diabetes.
• Heart disease and stroke. People who are obese are more likely to have high blood pressure, hardened arteries, high cholesterol, and other factors that can lead to heart disease and stroke.
• Sleep apnea. This sleep disorder is characterized by pauses in breathing during sleep. The disorder can cause daytime fatigue, high blood pressure and, rarely, sudden death. People with Prader-Willi syndrome may have sleep apnea or other sleep disorders even if they aren't obese, but obesity can worsen sleep problems.
• Other complications. Obese people, including those with Prader-Willi syndrome, are at increased risk of liver disease and can have pain in their joints due to excessive wear and tear.
Complications of hypogonadism
Complications may also arise from hypogonadism, a condition in which your sex organs don't secrete sufficient amounts of the sex hormones testosterone (males) and estrogen and progesterone (females). These may include:
• Sterility. Although there have been a few reports of women with Prader-Willi syndrome becoming pregnant, most people with this disorder are unable to have children.
• Osteoporosis. Osteoporosis is a condition characterized by weak and brittle bones, which can break easily. People with Prader-Willi syndrome are at an increased risk of developing osteoporosis because they have low levels of sex hormones and may also have low levels of growth hormone — both hormones help maintain strong bones.
Other complications
Other complications can arise from the complex nature of Prader-Willi syndrome:
• Effects of binge eating. Eating large amounts of food quickly, called binge eating, can cause your child's stomach to become abnormally distended (gastric dilatation). Individuals with Prader-Willi syndrome may not report pain and they rarely vomit. Binge eating can also cause choking and any of the other complications associated with obesity. Rarely, a person with Prader-Willi syndrome may eat so much that it causes stomach rupture.
• Significant behavior problems. Behavioral problems can interfere with family functioning and successful education and social participation. They can also reduce the quality of life for children, teenagers and adults with Prader-Willi syndrome.

Treatments
Prader-Willi syndrome cannot be cured. But, early intervention can help people build skills for adapting to the disorder. Early diagnosis can also help parents learn about the condition and prepare for future challenges. A health care provider can do a blood test to check for Prader-Willi syndrome.

Most children with Prader-Willi syndrome will need the following care and treatments:
• Good nutrition for infants. Many infants with Prader-Willi syndrome have difficulty feeding due to decreased muscle tone. Your child's health care provider may recommend a high-calorie formula or special feeding methods to help your baby gain weight and will monitor your child's growth.
• Human growth hormone treatment. Human growth hormone (HGH) stimulates growth and influences the body's conversion of food into energy (metabolism). Growth hormone treatment in children with Prader-Willi syndrome helps increase growth, and likely improves muscle tone and decreases body fat. Long-term effects of HGH treatment aren't known. A doctor who treats hormonal disorders (endocrinologist) can help determine whether your child would benefit from growth hormone treatment.
• Sex hormone treatment. Your endocrinologist may suggest that your child take hormone replacement therapy (testosterone for males or estrogen and progesterone for females) to replenish low levels of sex hormones. Hormone replacement therapy usually starts when your child reaches the normal age for puberty and can help reduce your child's risk of developing thinning of the bones (osteoporosis).
• Healthy diet. As your child gets older, a dietitian may help you develop a healthy, reduced-calorie diet to keep your child's weight under control while ensuring proper nutrition. Restricted access to food and strict supervision of food intake may be required.
• Treatment of sleep disturbances. Treating sleep apnea and other sleep problems can improve daytime sleepiness and behavioral issues. A sleep evaluation should be done before starting growth hormone treatment.
• Overall development. Your child will likely benefit from a range of therapies, including physical therapy to improve movement skills and strength, speech therapy to improve verbal skills, and occupational therapy to learn everyday skills. Developmental therapy to learn age-appropriate behaviors, social skills and interpersonal skills also may help. In the United States, early intervention programs providing these types of therapy are usually available for infants and toddlers through a state's health department.
• Mental health care. A mental health professional, such as a psychologist or a psychiatrist, may help address psychological problems your child may have — for example, obsessive-compulsive behaviors or a mood disorder. Some children may need medication to control behavioral problems.
Other treatments may be necessary, depending on the specific symptoms your child has or complications that develop.
Transition to adult care
Most people with Prader-Willi syndrome will need specialized care and supervision throughout their lives. Many adults with the disorder live in residential care facilities that enable them to eat healthy diets, live safely, work and enjoy leisure activities.
As your child approaches adulthood, consider these strategies:
• Find local resources and services through organizations such as the Prader-Willi Syndrome Association
• Investigate guardianship issues and wills regarding future care and supervision for your child
• Talk to your child's health care provider for suggestions about making the transition to adult medical care