Prader-Willi syndrome


Prader-Willi syndrome (PWS) is a genetic condition caused by the absence of chromosomal material from chromosome 15. Characteristics of the syndrome include developmental delays, poor muscle tone, short stature, small hands and feet, incomplete sexual development, and unique facial features. Insatiable appetite is a classic feature of PWS. This uncontrollable appetite can lead to morbid obesity and behavior disturbances.


The first patients with features of PWS were described by Dr. Prader, Dr. Willi, and Dr. Lambert in 1956. Since that time, the complex genetic basis of PWS has begun to be understood. Initially, scientists found that individuals with PWS have a portion of genetic material deleted (erased) from chromosome 15. In order to have PWS, the genetic material must be deleted from the chromosome 15 received from one's father. If the deletion is on the chromosome 15 inherited from one's mother, a different syndrome develops. This was an important discovery, for it demonstrated for the first time that the genes inherited from one's mother can be expressed differently than the genes inherited from one's father.

Over time, scientists realized that some individuals with PWS do not have genetic material deleted from chromosome 15. Further studies found that these patients inherit both copies of chromosome 15 from their mother, which is not typical. Normally, an individual receives one chromosome 15 from his or her father and one chromosome 15 from his or her mother. When a person receives both chromosomes from the same parent it is called "uniparental disomy." When a person receives both chromosomes from his or her mother, it is called "maternal uniparental disomy."

Scientists are still discovering other causes of PWS. A small number of patients with PWS have a change (mutation) in the genetic material on the chromosome 15 inherited from their father. This mutation prevents certain genes on chromosome 15 from working properly. PWS develops when these genes do not work normally.

Newborns with PWS generally have poor muscle tone, ( hypotonia ) and do not feed well. This can lead to poor weight gain and failure to thrive . Genitalia can be smaller than normal, and a male with PWS may have undescended testicles. Hands and feet are also typically smaller than normal. Some patients with PWS have unique and subtle facial characteristics that are detectable only by physicians.

As children with PWS age, development is typically slower than normal. Developmental milestones, such as crawling , walking and talking occur later than usual. Developmental delay continues into adulthood for approximately 50 percent of individuals with PWS. At about one to two years of age, children with PWS develop an uncontrollable, insatiable appetite. These children, if not controlled, will eat until they suffer from life-threatening obesity, including respiratory failure with hypoxia (low blood oxygen levels), cor pulmonale (right-sided heart failure), and death. The desire to eat can also lead to significant behavior problems.

The symptoms and features of PWS require lifelong support and care. If food intake is strictly monitored and various therapies provided, individuals with PWS have a normal life expectancy.

Prader-Willi syndrome is also referred to as cryptochidism-dwarfism-subnormal mentality syndrome, Willi-Prader syndrome, Labhart-Willi syndrome, Prader-Labhart-Will Fancone syndrome, and hypotoniahypomentia-hypogonadism-obesity syndrome.


PWS affects approximately one in 12,000 to 15,000 live births. It is the most common genetic cause of life-threatening obesity. It affects both males and females and can be seen in all races and ethnic groups.

Causes and symptoms

Human beings have 46 chromosomes in the cells of their body. Chromosomes contain genes that regulate the function and development of the body. An individual's chromosomes are inherited from his or her parents. Each parent normally gives a child 23 chromosomes. A child receives 23 chromosomes from the egg and 23 chromosomes from the sperm.

The 46 chromosomes in the human body are divided into pairs based on their physical characteristics. Each pair is assigned a number or a letter. When viewed under a microscope, chromosomes within the same pair appear identical because they contain the same genes.

Most chromosomes have a constriction near the center called the centromere. The centromere separates the chromosome into long and short arms. The short arm of a chromosome is called the p arm; the long arm and is called the q arm.

Chromosomes in the same pair contain the same genes. However, some genes work differently depending on if they were inherited from the egg or the sperm. Sometimes, genes are silenced when inherited from the mother. Other times, genes are silenced when inherited from the father. When genes in a certain region on a chromosome are silenced, they are said to be imprinted. Imprinting is a normal process that does not typically cause disease. However, if normal imprinting is disrupted, a genetic disease can develop.

Individuals have two complete copies of chromosome 15. One chromosome 15 is inherited from the mother, or is maternal in origin. The other chromosome 15 is inherited from the father, or is paternal in origin.

Chromosome 15 contains many different genes. There are several genes found on the q arm of chromosome 15 that are imprinted. A gene called SNPRN is an example of one of these genes. It is normally imprinted, or silenced, if inherited from the mother. The imprinting of this group of maternal genes does not typically cause disease. The genes in this region should not be imprinted if paternal in origin. Normal development depends on these paternal genes being present and active. If these genes are deleted, not inherited, or incorrectly imprinted, PWS develops.

Deletion in the paternally contributed chromosome 15

Seventy percent of the cases of PWS are caused when a piece of material is deleted, or erased, from the paternal chromosome 15. This deletion occurs in a specific region on the q arm of chromosome 15. The piece of chromosomal material that is deleted contains genes that must be present for normal development. These paternal genes must be working normally, because the same genes on the chromosome 15 inherited from the mother are imprinted. When these paternal genes are missing, the brain and other parts of the body do not develop as expected. This is what causes the symptoms associated with PWS.

In 99 percent of the cases of PWS, the deletion is sporadic. This means that it happens randomly, there is not an apparent cause, and the condition is not inherited. If a child has PWS due to a sporadic deletion in the paternal chromosome 15, the chance the parents could have another child with PWS is less than 1 percent. In fewer than 1 percent of the cases of PWS there is a chromosomal rearrangement in the family that causes the deletion. This chromosomal rearrangement is called translocation. If a parent has a translocation the risk of having a child with PWS is higher than 1 percent.

Maternal uniparental disomy

PWS can also develop if a child receives both chromosome 15s from his or her mother. This is seen in approximately 25 percent of the cases of PWS. Maternal uniparental disomy for chromosome 15 leads to PWS because the genes on chromosome 15 that should have been inherited from the father are missing, and the genes on both the chromosome 15s inherited from the mother are imprinted.

PWS caused by maternal uniparental is sporadic. This means that it occurs randomly and there is not an apparent cause. If a child has PWS due to maternal uniparental disomy, the chance the parents could have another child with PWS is less than 1 percent.

Error in imprinting process than renders paternal contribution non-functional

Approximately 2–5 percent of patients with PWS have a change (mutation) in a gene located on the q arm of chromosome 15. This mutation leads to incorrect imprinting. This mutation causes genes inherited from the father to be imprinted or silenced, which should not normally be imprinted. If a child has PWS due to a mutation that changes imprinting, the chance the parents could have another child with PWS is approximately 5 percent.

Signs of PWS can be seen at birth. Infants with PWS have weak muscle tone (hypotonia). This hypotonia causes problems with sucking and eating so that infants with PWS may initially have problems gaining weight. Consequently, some infants with PWS may be diagnosed with failure to thrive due to slow growth and development. Hypotonia may also During infancy, babies with PWS may also sleep more than normal and have problems controlling their temperature.

Some of the unique physical features associated with PWS can be seen during infancy. Genitalia ( hypogonadism ) that is smaller than normal is common. This may be more evident in males with PWS. Hands and feet may also be smaller than average. The unique facial features seen in some patients with PWS may be difficult to detect in infancy. These facial features are very mild and do not cause physical problems.

As early as six months, but more commonly at one to two years, a compulsive desire to eat develops. This uncontrollable appetite is a classic feature of PWS. Individuals with PWS lack the ability to feel full or satiated because of a flaw in the hypothalamus part of their brain, which normally registers feelings of hunger and satiety. Over-eating (hyperpahgia), a lack of a desire to exercise , and decreased calorie utilization (typically 1,000–1,200 calories per day for adults, due to low muscle mass and inactivity) places individuals with PWS at high risk for severe obesity. Obesity-related problems include hypoventilation, hyertension, right-sided heart failure, cellulitis, and skin problems with fat folds. Some individuals with PWS may also have a reduced ability to vomit.

Behavior problems are a common feature of PWS. Although infants and young children are typically happy and loving and exhibit few behavior problems, most older children and adults do have difficulties with behavior regulation, such as difficulties with transistions and unanticipated changes. Onset of behavioral problems usually coincides with the onset of the compulsive eating. Difficulties peak in adolescence or early adulthood. Reported problems include obsessive/compulsive behaviors, depression, temper tantrums and violent outbursts, and tendencies to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn. Individuals with PWS may also pick their own skin (skin picking). This unusual behavior may be due to a reduced pain threshold.

IQs range from 40 to 105, with an average of 70. Those with normal IQs typically have learning disabilities. Problem areas may include attention, short-term auditory memory, and abstract thinking. Common strengths include long-term memory, reading ability, and receptive language.

Puberty may occur early or late, but it is usually incomplete. In addition to the effects on sexual development and fertility, individuals do not undergo the normal adolescent growth spurt and may be short as adults. Muscles often remain underdeveloped and body fat is increased.

When to call the doctor

Parents should call a doctor if they notice symptoms that are characteristic of PWS.


During infancy the diagnosis of PWS may be suspected if poor muscle tone, feeding problems, small genitalia, or the unique facial features are present. If an infant has these features, testing for PWS should be performed. This testing should also be offered to children and adults who display features commonly seen in PWS (developmental delays, uncontrollable appetite, small genitalia, etc.). There are several different genetic tests that can detect PWS. All of these tests can be performed usnig a blood sample.

Methylation testing detects 99 percent of the cases of PWS. Methylation testing can detect the absence of the paternal genes that should be normally active on chromosome 15. Although methylation testing can accurately diagnose PWS, it can not determine if the PWS is caused by a deletion, maternal uniparental disomy, or a mutation that disrupts imprinting. This information is important for genetic counseling. Therefore, additional testing should be performed.

Chromosome analysis can determine if the PWS is the result of a deletion in the q arm of chromosome 15. Chromosome analysis, also called karyotyping, involves staining the chromosomes and examining them under a microscope. In some cases the deletion of material from chromosome 15 can be easily seen. In other cases, further testing must be performed. FISH (fluorescence in-situ hybridization) is a special technique that detects small deletions that cause PWS.

More specialized DNA testing is required to detect maternal uniparental disomy or a mutation that disrupts imprinting. This DNA testing identifies unique DNA patterns in the mother and father. The unique DNA patterns are then compared with the DNA from the child with PWS.

PWS can be detected before birth if the mother undergoes amniocentesis testing or chorionic villus sampling (CVS). This testing is only recommended if the mother or father is known to have a chromosome rearrangement, or if they already have a child with PWS syndrome.


There is currently not a cure for PWS. Treatment during infancy includes therapies to improve muscle tone. Some infants with PWS also require special nipples or tube feeding to improve weight gain.

Growth hormone therapy has been shown to improve the poor muscle tone and reduced height typically associated with PWS. Hypogonadism may be corrected at puberty with hormone replacement. Skin picking is best managed by ignoring the behavior, treating and bandaging sores, and providing substitute activities for the hands. Other behavioral problems can be managed through daily routines and structure, firm rules and limits, "time outs," positive rewards, and the use of psychotropic drugs.

Special education may be helpful in treating developmental delays and behavior problems. Individuals with PWS typically excel in highly structured environments. Physical and occupational therapies promote skill development and proper function. Exercise and sport activities should be encouraged, with adaptations made as necessary. Proficiency with jigsaw puzzles have been frequently reported, reflecting strong visual-perceptual skills. The need for speech therapy, due to speech difficulties caused by hypotonia, should be assessed. Sign language and picture communication boards can be used to reduce frustration and to aid communication. Products to increase saliva may help articulation problems. Social skills training can improve pragmatic language use. Verbal ability often becomes an area of strength for children with PWS.

Nutritional concerns

Treatment and management of PWS during childhood, adolescence, and adulthood is typically focused on weight control. Strict control of food intake is vital to prevent severe obesity. In many cases food must be made inaccessible. This may involve unconventional measures such as locking the refrigerator or kitchen cabinets. A lifelong balanced restricted-calorie diet with vitamin and calcium supplementation and a regular exercise program (at least 30 minutes per day) are also suggested. The best meal and snack plan is one that the family or caregiver is able to aply routinely and consistently. Unfortunately, diet medications nor surgery have not been shown to significantly prevent obesity in PWS or eliminate the need for strict dieting and supervision around food.


With help, people with PWS can expect to accomplish many of the things their "normal" peers do: complete school, achieve in their outside areas of interest, be successfully employed, and even move away from their family home. They do, however, need a significant amount of support from their families and from school, work, and residential service providers to both achieve these goals and to avoid obesity and the serious health consequences that accompany it. Even those with IQs in the normal range need lifelong diet supervision and protection from food availability.

Although in the past many people with PWS died in adolescence or young adulthood, prevention of obesity can enable those with the syndrome to live a normal lifespan. New medications, including psychotropic drugs and synthetic growth hormone, are already improving the quality of life for some people with PWS. Ongoing research offers the hope of new discoveries that will enable people affected by this unusual condition to live more independent lives.


Centromere —The constricted region of a chromosome. It performs certain functions during cell division.

Deletion —The absence of genetic material that is normally found in a chromosome. Often, the genetic material is missing due to an error in replication of an egg or sperm cell.

DNA —Deoxyribonucleic acid; the genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.

Fluorescence in situ hybridization (FISH) —A technique for diagnosing genetic disorders before birth by analyzing cells obtained by amniocentesis with DNA probes.

Gene —A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.

Hyperphagia —Over-eating.

Hypotonia —Having reduced or diminished muscle tone or strength.

Imprinting —A process that silences a gene or group of genes. The genes are silenced depending on whether they are inherited through the egg or the sperm.

Maternal uniparental disomy —A chromosome abnormality in which both chromosomes in a pair are inherited from one's mother.

Methylation testing —DNA testing that detects if a gene is active or if it is imprinted.

Mutation —A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease. This change can be transmitted to offspring.

Translocation —The transfer of one part of a chromosome to another chromosome during cell division. A balanced translocation occurs when pieces from two different chromosomes exchange places without loss or gain of any chromosome material. An unbalanced translocation involves the unequal loss or gain of genetic information between two chromosomes.

Uniparental disomy —Chromosome abnormality in which both chromosomes in a pair are inherited from the same parent.


PWS currently cannot be prevented. Genetic counseling is recommended for parents who may be at risk for having a child with PWS.

Parental concerns

While there is no medical prevention or cure, early diagnosis of Prader-Willi syndrome gives parents time to learn about and prepare for the challenges that lie ahead and to establish family routines that will support their child's diet and behavior needs. The constant need for food restriction and behavior management may be stressful for family members. It is also important for the parents to provide basic sex education to promote good health and to protect against abuse. Knowing the cause of their child's developmental delays can facilitate a family's access to important early intervention services and may help program staff identify areas of specific need or risk. Additionally, a diagnosis of PWS opens the doors to a network of information and support from professionals and other families who are dealing with the syndrome. Adolescents and adults with PWS can function well in group and supported living programs, if the necessary diet control and structured environment are provided. Employment in sheltered workshops and other highly structured and supervised settings is successful for many. However, residential and vocational providers must be fully informed regarding management of PWS.



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Alliance of Genetic Support Groups. 4301 Connecticut Ave. NW, Suite 404, Washington DC 20008. (202) 966-5557. Fax: (202) 966-8553.

International Prader-Willi Syndrome Organization.

National Organization for Rare Disorders, Inc. P.O. Box 8923, New Fairfield, CT 06812. (800) 999-6673.

Prader-Willi Foundation. 223 Main Street, Port Washington, NY 11050. (800)253-7993.

Prader-Willi Syndrome Association (USA). 5700 Midnight Pass Rd., Sarasota, FL 34242. (800) 926-4797.


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Judith Sims, MS Holly Ann Ishmael, MS

Also read article about Prader-Willi Syndrome from Wikipedia

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