Prader-Willi syndrome

Definition

Prader-Willi syndrome is a rare genetic disorder characterized by decreased muscle tone, mental retardation and an intense desire to eat, which can lead to morbid obesity. Behavioral problems, such as temper tantrums or unusual food-seeking behavior, also are common features of this disorder. Prader-Willi syndrome is usually diagnosed by early childhood.

Initially, infants with Prader-Willi syndrome often have difficulty feeding but at about 1 year of age, children with this disorder develop voracious appetites and will gain weight quickly if their access to food is uncontrolled. Many of the complications from Prader-Willi syndrome are due to obesity.

There's no cure for Prader-Willi syndrome, but a team of specialists may work with you to manage your child's signs and symptoms and reduce the risk of developing complications.

Symptoms

Some signs and symptoms of Prader-Willi syndrome become evident shortly after birth. These may include:

• Poor muscle tone. A classical feature of babies with Prader-Willi syndrome is poor muscle tone (hypotonia). Hypotonic babies rest with their elbows and knees loosely extended instead of fixed and feel floppy or like "rag-dolls" when they're held.
• Distinct facial features. Children with Prader-Willi syndrome are often born with almond-shaped eyes, narrowing at the temples, a turned-down mouth and a thin upper lip.
• Failure to thrive. During the first year of life, children with Prader-Willi syndrome may have a poor sucking reflex due to decreased muscle tone. This makes feeding difficult, so they tend to gain weight slowly.

A weak cry and crossing of the eyes (strabismus) are other signs and symptoms of infants with Prader-Willi syndrome.

After the first year of life and into early childhood, children with Prader-Willi syndrome usually develop voracious appetites. They constantly crave food and tend to become morbidly obese if their food intake is left unchecked. Other signs and symptoms recognizable at this stage may include:

• Underdeveloped sex organs. A condition called hypogonadism occurs when sex organs — the testes in men and the ovaries in women — produce little or no sex hormones. Children with Prader-Willi syndrome have underdeveloped sex organs.
• Learning disabilities. Mild to moderate retardation is a common feature of children with Prader-Willi syndrome.
• Delayed motor development. Toddlers with Prader-Willi syndrome often reach motor milestones, such as sitting at 12 months and walking at 24 months, later than other children.
• Behavioral problems. In general, children with Prader-Willi syndrome are happy and pleasant to be around. However, these children may become very stubborn or throw temper tantrums, especially when denied food. They may also develop obsessive-compulsive disorders or unusual food-seeking behavior, such as eating garbage or frozen food.

Other signs and symptoms of young children with Prader-Willi syndrome may include:

• Short stature
• Small hands and feet
• Nearsightedness (myopia)
• Loss of skin pigmentation
• Stretch marks (stria)
• High pain tolerance
• Skin picking

As children with Prader-Willi syndrome enter adolescence, they may develop pubic and underarm hair, but other secondary sex characteristics, such as testicular development in men or menarche in women, may be delayed or may not occur at all.

Causes

Genes are segments of DNA that provide the "blueprints" for all of your characteristics — everything from hair color to the propensity to develop certain cancers. You receive your genes, which occur in pairs, from your parents. One copy comes from your mother, called the maternal copy, and the other copy comes from your father, the paternal copy.

Usually, both genes in each pair are "active" — meaning that information from both the maternal copy and the paternal copy of each gene pair are used by your cells. But in a small number of genes, only one copy of a gene pair is expressed — and the activity of each gene copy depends on whether it was passed from your mother or from your father. This is called imprinting.

Such is the case with Prader-Willi syndrome. A portion of the paternal gene copy on a region of chromosome 15 is either inactive or defective. Since the maternal gene copy in this pair is usually inactive, no active or normal gene copy remains — and Prader-Willi syndrome results.

Prader-Willi syndrome affects a portion of your child's brain called the hypothalamus. Among its many functions, the hypothalamus controls hunger and thirst and releases hormones that prompt the release of other substances responsible for growth and sexual development. A malfunctioning hypothalamus — caused by the defect on chromosome 15 — interferes with each of these processes, resulting in uncontrollable hunger, stunted growth and sexual underdevelopment in children with Prader-Willi syndrome.

A region in your brain called the hypothalamus controls many functions in your body. A malfunctioning hypothalamus caused by a defect on chromosome 15 results in uncontrollable hunger, stunted growth and sexual underdevelopment, which are common features of Prader-Willi syndrome.

Risk factors

Defective or missing portions of the paternal gene copy responsible for Prader-Willi syndrome usually occur sporadically. This means that in most instances, Prader-Willi syndrome can't be prevented. However, in a small number of cases, a genetic mutation inherited from the father may cause Prader-Willi syndrome. If you have a child with Prader-Willi syndrome and would like to have another baby, consider seeking genetic counseling. A genetic counselor can help determine your risk of having another child with Prader-Willi syndrome.

When to seek medical advice

Call your doctor if your child complains of severe abdominal pain, has a decreased appetite or appears bloated. These may indicate gastric dilatation, a condition in which your child's stomach is stretched beyond its normal capacity to hold food. Rarely, gastric dilatation can cause the stomach wall to rupture and spill its contents into the abdominal cavity, which can be fatal. Some children with Prader-Willi syndrome have a high pain tolerance, so it's important to get your child checked if he or she isn't behaving normally.

Tests and diagnosis

Your doctor may suspect that your child has Prader-Willi syndrome at birth if your child has the characteristic facial features — almond-shaped eyes, a misalignment of the eyes (strabismus), narrowing at the temples, a turned-down mouth and a thin upper lip — and other signs of the disorder, such as floppiness (hypotonia) and underdeveloped reproductive organs.

To confirm the suspected diagnosis, your doctor obtains a blood sample from your child to perform genetic testing. A karyotype is a genetic testing technique in which your child's chromosomes are stained and arranged by pairs in numerical order on film. By examining each chromosome pair, your doctor can determine whether the chromosomes are abnormally shaped or missing. A specialized genetic test called a methylation analysis is very sensitive and can detect nearly every case of Prader-Willi syndrome.

Complications

Many of the major complications of Prader-Willi syndrome result from morbid obesity caused by uncontrolled eating. These complications may include:

• Diabetes. Diabetes is a condition characterized by high blood sugar levels, which occurs when your body doesn't make the hormone insulin or isn't able to use it efficiently. Insulin plays a vital role in making blood sugar (glucose) — your body's fuel — available to your cells. Obesity increases your child's risk of developing diabetes.
• High blood pressure. This commonly occurs in people who are obese because your heart has to work harder to pump blood throughout a body that's carrying extra weight.
• Cor pulmonale. This is a type of right-sided heart failure that results when your heart has difficulty pumping blood to your lungs. Cor pulmonale can occur if your child has lung problems.
• Bone and joint problems. Carrying around extra weight stresses your child's bones and joints.
• Sleep apnea. This is a sleep disorder characterized by pauses in breathing during sleep. Sleep apnea can cause daytime fatigue, high blood pressure and, rarely, lead to sudden death. Obesity increases the risk of developing sleep apnea because excessive fat in the throat and neck can interfere with your child's breathing.

Complications of hypogonadism
Other complications 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 (sterile).
• Osteoporosis. Osteoporosis refers to weakened and brittle bones. Children with Prader-Willi syndrome are at an increased risk of developing osteoporosis because they have low levels of sex hormones, which help maintain strong bones.

Eating large amounts of food quickly, called binge eating, can cause your child's stomach to become abnormally distended (gastric dilatation). Rarely, an abnormally distended stomach can cause the stomach wall to rupture, which can be fatal.

Treatments and drugs

A team of health professionals will likely work with you to manage your child's condition. Depending on your child's signs and symptoms, treatment for Prader-Willi syndrome may involve the following:

• Encouraging feeding during infancy. Many infants with Prader-Willi syndrome have difficulty feeding due to decreased muscle tone. Your pediatrician may recommend a high-calorie formula to help your baby gain weight and will likely monitor your child's development as he or she begins to grow.

• Replenishing hormone deficiencies. Human growth hormone stimulates bone growth and muscle and organ development. Some studies have suggested that growth hormone treatment in children with Prader-Willi syndrome helps increase growth and decrease body fat, but the long-term effects of growth hormone treatment aren't known. A doctor who treats hormonal disorders (endocrinologist) can help determine whether your child would benefit from growth hormone treatment.

  Your endocrinologist may also 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 can help decrease your child's risk of developing thinning of the bones (osteoporosis).

• Following a low-calorie diet. A nutritionist may help you develop a healthy, reduced-calorie diet to keep your child's weight under control. However, to ensure proper nerve cell development in the first few years of life, a low-calorie diet isn't recommended for children under the age of 3.
• Improving motor skills. Physical therapists may guide your child through exercises to help him or her maintain a healthy weight, develop motor skills and strengthen back muscles to help prevent an abnormal curving of the spine (scoliosis).
• Correcting vision problems. Some children with Prader-Willi syndrome have crossed eyes (strabismus). A doctor who specializes in disorders of the eyes (ophthalmologist) may prescribe glasses, eye exercises or a patch that's placed over your child's normal eye to help improve strabismus.
• Treating sleep apnea. Sleep apnea, or pauses in breathing during sleep, can be serious because it can cause high blood pressure and rarely, sudden death. A doctor who specializes in lung problems (pulmonologist) may recommend surgery, an oral device to keep your child's throat open or another therapy.
• Addressing psychological disorders. A mental health professional, such as a psychologist or a psychiatrist, may help address any psychological problems your child may have, such as obsessive-compulsive tendencies or mood disorders. Some children may need medication to control behavioral problems.

Lifestyle and home remedies

Children with Prader-Willi syndrome require lifelong care, but with proper management these children can expect to lead full lives. Here are some tips to help you take care of your child with Prader-Willi syndrome:

• Pick up your child carefully. Children with Prader-Willi syndrome often have poor muscle tone, which increases their risk of slipping between your hands when you lift them under their armpits.
• Take steps to help prevent binge eating. Adhering to a low-calorie diet is essential to keep your child from becoming overweight. Try to avoid purchasing high-calorie snacks. Store food out of your child's reach, lock pantries, refrigerators and cupboards, and use small dishes for serving meals.
• Supplement your child's diet. If your child is on a restricted-calorie diet, ask your doctor if supplemental vitamins or minerals are necessary to ensure balanced nutrition.
• Schedule appropriate screening tests. Be sure to talk to your doctor about having your child screened for complications of Prader-Willi syndrome, including diabetes, osteoporosis and an abnormally curved spine (scoliosis).

Coping and support

Having a child with Prader-Willi syndrome and its associated behavioral problems is challenging and can take a lot of patience. Ask your doctor about support groups in your area for parents dealing with serious behavioral issues stemming from Prader-Willi syndrome.