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Prader-Willi syndrome: causes and therapy

by Josephine Andrews
Published: Last Updated on 232 views

Prader-Willi syndrome (PWS) is the result of a congenital defect in the genetic material . Affected infants are short in stature, mentally underdeveloped, and weak in muscles. In infancy, they develop an insatiable hunger that easily leads to severe obesity. This in turn is associated with numerous secondary diseases. Read more about the symptoms, diagnosis and treatment of Prader-Willi syndrome here.

ICD codes for this disease:

ICD codes are internationally valid codes for medical diagnoses. They can be found, for example, in doctor’s letters or on certificates of incapacity for work.


quick overview

  • Symptoms: Pronounced muscle weakness, lack of feeling of satiety when eating too much, changed facial features, short stature, developmental delays, disturbed puberty development
  • Course and prognosis: Prader-Willi syndrome requires comprehensive medical care to counteract complications. Life expectancy is usually normal if body weight is managed.
  • Causes: The cause of Prader-Willi syndrome is a genetic change in chromosome 15.
  • Diagnosis: The diagnosis can usually be made on the basis of the typical physical symptoms, with confirmation being provided by genetic analysis.
  • Treatment: The treatment is carried out by various specialists, the focus is on controlling food intake, normalizing growth and providing psychosocial support.
  • Prevention: The genetic disease cannot be prevented, but its consequences can be curbed with optimal therapy.

What is Prader-Willi Syndrome?

The Prader-Willi syndrome (incorrectly also Willi-Prader syndrome) was first described in 1956 by the pediatricians Andrea Prader, Alexis Labhart and Heinrich Willi. It is a rare developmental disorder of the nervous system. This leads to a dysfunction of the hypothalamus , an important control center in the brain .

The hypothalamus controls processes such as water and salt balance, breathing , blood pressure, body temperature and food intake, but also emotional behavior. In addition, the hypothalamus produces various hormones . These in turn regulate the formation of other hormones or have a direct effect on their target organs.

These target organs include but are not limited to the thyroid gland, genitals and kidneys. Growth is also under the control of hormones produced in the hypothalamus.

About one in 15,000 newborns is born with Prader-Willi syndrome. The individual manifestation of the PWS is very different and complex.

What are the symptoms of Prader-Willi Syndrome?

Even before birth , affected children are conspicuous because they move very little in the womb. The heart rate is lower than normal. Babies need a lot of support both during and after birth.

Immediately after birth, affected babies are noticed by their lack of movement, (muscle) and a low birth weight. Many newborns do not start crying or cry very weakly. Because of the pronounced muscle weakness and the resulting sucking and swallowing disorders, babies find it difficult to drink. They are often underweight and gain weight slowly.

Overall, the babies are often remarkably quiet and sleep a lot. Babies with Prader-Willi syndrome also look different. Typical external symptoms include a long, narrow face with almond-shaped eyes, a thin upper lip, and a downturned mouth.

The skull is often long (dolidochocephaly), hands and feet are small. Some children have an S-shaped spine (scoliosis ). The bone substance in the whole body shows damage and defects (osteoporosis/osteopenia) in the X-ray image. The pigmentation of skin, hair and retina is partially reduced.

Visual disturbances and squinting ( strabismus ) of the eyes are also possible. The scrotum is small and often empty (undescended testicles). Overall, children’s development is delayed.

By the end of the first year of life, the muscle weakness improves somewhat and the children often become more lively. However, there is always at least a mild weakness.

Normal activities are therefore quickly tiring and tiring for patients with Prader-Willi syndrome. Nevertheless, children enjoy age-appropriate activities just as much as healthy children. In infancy, affected children grow much more slowly.

Uninhibited food intake

The hypothalamus controls food intake, among other things. Due to its malfunction, affected children in infancy begin to eat excessively and uninhibitedly (hyperphagia). The reason for this is that they do not feel full.

Since the children take in far more calories than they need as a result, Prader-Willi syndrome usually leads to severe obesity (obesity) in early childhood. Those affected find it extremely difficult to control their eating habits. Children tend to hoard food and are very resourceful when it comes to finding food.

Being overweight brings with it typical and sometimes serious secondary diseases: the heart and lungs suffer from the stress caused by obesity. A quarter of all those affected develop diabetes mellitus by the age of 20.

Other symptoms of Prader-Willi syndrome include sleep disorders, venous disease (thrombophlebitis) and water retention. In the course of the disease, sleep disturbances are sometimes added. In addition to repeated pauses in breathing, disruptions to the day-night rhythm or even deep sleep are possible.

Puberty development is disturbed

The growth spurt typical of healthy adolescents during puberty is minor in adolescents with Prader-Willi syndrome. Affected children usually do not get taller than 140 to 160 centimeters.

Although puberty sometimes begins prematurely, in many cases the development of puberty does not come to an end. Those affected therefore usually remain infertile.

In boys, the penis and especially the testicles remain small. Pigmentation and wrinkles are absent on the scrotum. The voice may not break.

In girls, the labia and clitoris remain underdeveloped. The first menstrual bleeding does not occur at all, occurs prematurely or very late, sometimes between the ages of 30 and 40.

Mental and intellectual development

Both mental and psychomotor development are disturbed in Prader-Willi syndrome. Affected children often reach the milestones of childhood development later than their healthy peers. Language and motor development sometimes take twice as long.

The intellectual disability in Prader-Willi syndrome is usually mild to moderate, the average intelligence quotient (IQ) is between 60 and 70. Around 40 percent of those affected are on the verge of mental disability. Regardless of IQ, learning disabilities show up as arithmetic difficulties. School performance is usually below average.

Affected children also show abnormalities in emotional development and behavior. You may seem stubborn at times and can be quick-tempered. Tantrums are not uncommon due to lack of impulse control.

Sometimes psychiatric abnormalities appear in early childhood: some children are very possessive and behave defiantly and hostilely towards others (oppositional behavioral disorder). Some children with PWS have compulsive repetition of certain routines. Around 25 percent of those affected show autistic traits. Attention Deficit Disorder (ADD) is also common.

The symptoms usually increase with age and obesity. In older adults, however, Prader-Willi syndrome symptoms often resolve slightly. Around ten percent suffer from psychosis. In addition, epilepsies and forms of “sleep addiction” (narcolepsy) occur in Prader-Willi syndrome.  

What is Prader-Willi Syndrome?

In principle, a fulfilling life is possible for people with Prader-Willi syndrome. Above all, an early diagnosis has a positive influence on the long-term prognosis of people with Prader-Willi syndrome. In particular, the quality of life of children can be improved if parents or caregivers control their eating behavior as much as possible from the start and reduce the risk of obesity.

Taking growth hormones also often contributes to a better quality of life, especially since the body mass index may stabilize as a result of growth.

In children with Prader-Willi syndrome, it is advisable to carefully monitor the development, behavior, growth, and body weight, including looking for psychiatric abnormalities. This makes it possible to react quickly and take countermeasures if problems arise.

The greatest risk for people with Prader-Willi Syndrome is increasing obesity and the complications it causes. The otherwise largely normal life expectancy also decreases in the case of pronounced obesity. The increased mortality is mainly due to secondary diseases of the heart, blood vessels and lungs.

People with Prader-Willi syndrome often achieve some degree of independence, but not full autonomy.

Causes and risk factors

The cause of Prader-Willi syndrome is a dysfunction of the hypothalamus, part of the midbrain. This causes, among other things, a deficiency of the important growth hormone. In around three quarters of cases, the disorder is due to a missing gene segment in chromosome 15 (15q11-q13). The corresponding gene segment is only present once in those affected, instead of twice as is normally the case, namely on the paternal and maternal chromosome.

In Prader-Willi syndrome, the paternal gene copy is usually missing (70 to 75 percent of those affected). While a single intact copy is sufficient for many other genes, this is not the case for the corresponding region on chromosome 15. The remaining maternal copy is not able to replace the missing paternal copy.

The reason for this is a special feature of this chromosome segment: it is normally shut down on the maternal chromosome, so that only the paternal copy is visible, even in healthy people. Doctors refer to this mechanism as “imprinting”. In people who lack the active paternal copy, only the silenced and therefore non-functional maternal gene segment is present.

Another possibility is that people with Prader-Willi syndrome have two copies of the chromosome segment, but both come from the mother (uniparental disomy, 25 to 30 percent). Due to the imprinting of the maternal chromosome segment, both gene copies are silenced in this case.

A so-called “imprinting defect” is even rarer (one percent). Both a maternal and a paternal gene copy are present in those affected, but both copies are erroneously shut down, including those from the father.

In most cases, the disorder is not hereditary. It usually only develops during germ cell development or after fertilization. In rare cases, however, it is also possible that already existing gene mutations cause Prader-Willi syndrome. In these cases, the risk of inheritance is increased. If a child has PWS, it is therefore advisable for parents who wish to have more children to seek advice from a human geneticist.

investigations and diagnosis

Newborns with persistent and unexplained weakness may have Prader-Willi syndrome. A first suspicion usually arises when the newborn doctor (neonatologist) or the pediatrician examines the newborn for the first time.

Physical examination

The main characteristic of the Prader-Willi syndrome is the pronounced weakness, which is particularly evident when drinking. Appearance also gives clues. Various reflexes are poorly developed in newborns with Prader-Willi syndrome.

In older people affected, a lack of growth hormone that can be measured in the blood is diagnostically helpful. The concentration of sex hormones (oestrogen, testosterone, FSH, LH) is also usually reduced. This is accompanied by an underdevelopment of the sex organs. The function of the adrenal cortex is disturbed in many cases. As a result, the formation of sex hormones may begin prematurely.

The examination of the brain waves (electroencephalogram, EEG) is also noticeable in some of those affected.

Genetic examination

Genetic testing is needed to confirm suspicion of Prader-Willi syndrome because some other disorders cause similar symptoms.

These disorders include Martin-Bell syndrome and Angelmann syndrome. However, the disorder in Martin-Bell syndrome is on the X chromosome , one of the two sex chromosomes (fragile X syndrome). In most cases, the same position on chromosome 15 is deleted in Angelmann syndrome – in contrast to PWS, however, only that position on the maternal chromosome.


Prader-Willi syndrome cannot be cured. However, with the help of consistent supportive therapy, the symptoms can be alleviated. The main components of treatment are dietary control, hormone replacement therapy , and treatment of behavioral problems.

For optimal treatment, it makes sense to have the child’s activity and motor development checked regularly by a doctor. If necessary, it is possible to support the development with physiotherapy or similar methods.

Due to the disturbances in bone metabolism, the pediatrician should also check the skeletal development regularly.


Adequate nutrition is important in infancy, especially if the muscle weakness is severe. To facilitate feeding and to ensure that the child grows enough, there is an option to insert probes or special artificial nipples. In addition, a feeding plan is advisable in which calorie intake and weight control are well documented.

As children grow older, they develop an overeating disorder. Then it is important to stick to a meal plan with a precisely defined calorie intake. Parents may need to tightly control access to food.

The eating disorder in PWS has a particularly serious effect on the course of the disease, since those affected move little in addition to the increased calorie intake. Serious obesity with the associated secondary diseases can easily develop.

These sometimes limit the life expectancy of people with Prader-Willi syndrome. It is therefore crucial that affected children learn at an early age, with the help of their parents or carers, how to handle food properly.

Despite strict calorie limitation, it is important that those affected are adequately supplied with vitamins and minerals through food. Bone metabolism disorders are common in Prader-Willi syndrome. Therefore, it may make sense to take vitamin D and calcium.

growth and sex hormones

In the meantime, it is common practice to administer growth hormones in infancy in Prader-Willi syndrome. This therapy has a significant effect on the physical development of the children and is useful until the growth plates in the bones have closed (X-ray control).

As with any therapy, side effects are possible when taking growth hormones. These include water retention on the feet (foot oedema), worsening of the curvature of the spine (scoliosis) or an increase in pressure in the skull. At the beginning of therapy, breathing disorders sometimes occur. During this period, it is important to monitor sleep.

In the case of puberty disorders, the symptoms can be alleviated by sex hormones. These are available as depot injections, hormone patches or gel. Under certain circumstances, the use of sex hormones also improves the behavioral problems. Estrogens also support bone formation, but also have a variety of side effects.

In principle, regular check-ups with the doctor are useful during hormone therapy in order to check the success of the treatment and to identify side effects at an early stage.

psychological promotion

Affected children need help with behavioral development. It is particularly important with Prader-Willi syndrome to train social skills with the child and to promote interactions with peers and caregivers. At school, some children require one-on-one attention.

In the case of adult sufferers, it may be necessary to adapt the living and working environment. In some cases, psychiatric abnormalities require drug therapy. The aim of the intensive support is the best possible independence for those affected.

surgical care

Surgical interventions are sometimes useful in Prader-Willi syndrome to alleviate certain symptoms. For example, children with Prader-Willi syndrome are more likely to suffer from a misalignment of their eyes. A squint position in particular can be treated surgically to prevent visual disturbances. Sometimes it is sufficient to temporarily cover the healthy eye.

Underdevelopment of the sex organs may also require surgery to move the testicle from the lower abdomen into the scrotum. Sometimes hormone treatment helps enlarge the scrotum, allowing the testicle to descend.

In severe cases, an S-position of the spine (scoliosis) requires surgical correction.


Since the Prader-Willi syndrome is based on a genetic defect, the disease cannot be prevented. However, serious secondary diseases and complications can be prevented. Above all, parents and carers should train their children early on in handling food and strictly control their calorie intake.

In addition, the course of the disease can be positively influenced by taking growth and sex hormones and regular check-ups by the appropriate specialists.

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