Brief overview
- Symptoms: Pronounced muscle weakness, lack of satiety with excessive food intake, altered facial features, short stature, developmental delays, impaired pubertal development
- Progression and prognosis: Prader-Willi syndrome requires comprehensive medical care to counteract complications. Life expectancy is usually normal if body weight can be controlled.
- Causes: Prader-Willi syndrome is caused by a genetic change in chromosome 15.
- Diagnosis: Diagnosis is usually possible on the basis of the typical physical symptoms; confirmation is provided by genetic analysis.
- Treatment: Treatment is carried out by various specialists, with the focus on controlling food intake, normalizing growth and providing psychosocial support.
- Prevention: The genetic disease cannot be prevented, but its consequences can be contained through optimal therapy.
What is Prader-Willi syndrome?
The hypothalamus controls processes such as water and salt balance, respiration, blood pressure, body temperature and food intake, as well as emotional behavior. The hypothalamus also produces various hormones. These in turn regulate the production of other hormones or have a direct effect on their target organs.
These target organs include the thyroid gland, the reproductive organs and the kidneys. Growth is also subject to the control of hormones that are produced in the hypothalamus.
Around one in 15,000 newborns is born with Prader-Willi syndrome. The individual manifestations of PWS vary greatly and are complex.
What are the symptoms of Prader-Willi syndrome?
Affected children are conspicuous even before birth, as they move very little in the womb. The heart rate is lower than normal. The babies need a lot of support both during and after birth.
Overall, the babies are often noticeably quiet and sleep a lot. Babies with Prader-Willi syndrome also look different. Typical external symptoms include, for example, a long, narrow face with almond-shaped eyes, a thin upper lip and a downturned mouth.
The skull is often long (dolidochocephaly) and the hands and feet are small. In some children, the spine is bent in an S-shape (scoliosis). The bone substance in the whole body shows damage and deficiencies on X-ray (osteoporosis/osteopenia). The pigmentation of the skin, hair and retina is partially reduced.
Visual disturbances and strabismus of the eyes are also possible. The scrotum is small and often empty (undescended testicles). Overall, the child’s development is delayed.
Towards the end of the first year of life, the muscle weakness improves somewhat and the children often become livelier. However, there is always at least mild weakness.
Uninhibited food intake
Among other things, the hypothalamus controls food intake. Due to its malfunction, affected children begin to eat uninhibitedly and excessively during infancy (hyperphagia). The reason for this is that they do not feel full.
As this causes children to consume far more calories than they need, Prader-Willi syndrome usually leads to severe obesity in early childhood. Those affected find it extremely difficult to control their eating behavior. The children tend to hoard food and are very inventive when it comes to obtaining food.
Obesity brings with it typical and sometimes serious secondary diseases: the heart and lungs suffer from the strain of obesity. A quarter of all those affected develop diabetes mellitus by the age of 20.
Puberty development is disturbed
The growth spurt typical of healthy adolescents during puberty is low in adolescents with Prader-Willi syndrome. Affected children usually do not grow taller than 140 to 160 centimeters.
Although puberty begins prematurely in some cases, pubertal development is not completed in many cases. Those affected therefore usually remain infertile.
In boys, the penis and especially the testicles remain small. There is a lack of pigmentation and folds on the scrotum. The voice may also not break.
In girls, the labia and clitoris remain underdeveloped. The first menstrual period does not occur at all, is premature or very late, sometimes only between the ages of 30 and 40.
Psychological and mental development
Both mental and psychomotor development are impaired 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.
Affected children also show abnormalities in their emotional development and behavior. They sometimes appear stubborn and may be quick-tempered. Tantrums are not uncommon due to a lack of impulse control.
Sometimes psychiatric abnormalities already occur in early childhood: Some children are very possessive and behave defiantly and hostile towards others (oppositional behavior disorder). Some children with PWS have to repeat certain routines compulsively. Around 25 percent of those affected show autistic traits. Attention deficit disorder (ADD) also occurs more frequently.
The symptoms usually increase with age and obesity. In older adults, however, Prader-Willi syndrome symptoms often regress slightly. Around ten percent suffer from psychoses. Epilepsy and forms of “sleep addiction” (narcolepsy) also occur in Prader-Willi syndrome.
How does Prader-Willi syndrome progress?
Taking growth hormones also often contributes to a higher quality of life, especially as growth may stabilize the body mass index.
It is advisable to carefully monitor the development, behavior, growth and body weight of children with Prader-Willi syndrome and also to pay attention to 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 resulting complications. Life expectancy, which is otherwise largely normal, 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 a certain degree of independence, but not complete autonomy.
Causes and risk factors
The reason for this is a special feature of this section of the chromosome: it is normally silenced on the maternal chromosome, so that only the paternal copy ever comes into play – 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 although two copies of the chromosome segment are present in people with Prader-Willi syndrome, they both originate 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). In these affected individuals, both a maternal and a paternal gene copy are present, but both copies are incorrectly silenced, including the one from the father.
Examinations and diagnosis
Newborns with persistent and unexplained weakness may have Prader-Willi syndrome. An initial suspicion usually arises when the neonatologist or pediatrician examines the newborn for the first time.
Physical examination
The main sign of Prader-Willi syndrome is pronounced weakness, which is particularly noticeable when drinking. The appearance also provides clues. Various reflexes are weak in newborns with Prader-Willi syndrome.
In older sufferers, a measurable deficiency of growth hormone in the blood is diagnostically helpful. The concentration of sex hormones (oestrogen, testosterone, FSH, LH) is also usually reduced. This is accompanied by underdevelopment of the sexual organs. The function of the adrenal cortex is impaired in many cases. As a result, the production of sex hormones may begin prematurely.
The examination of brain waves (electroencephalogram, EEG) is also conspicuous in some affected persons.
Genetic examination
These disorders include Martin Bell syndrome and Angelmann syndrome. However, the disorder in Martin-Bell syndrome is located on the X chromosome, one of the two sex chromosomes (fragile X syndrome). In Angelmann syndrome, the same site on chromosome 15 is deleted in most cases – in contrast to PWS, however, only the site on the maternal chromosome is deleted.
Treatment
Prader-Willi syndrome cannot be cured. However, the symptoms can be alleviated with the help of consistent supportive therapy. The most important components of treatment are food control, hormone replacement therapy and the treatment of behavioral problems.
For optimal treatment, it makes sense to have the activity and motor development of the sick child checked regularly by the doctor. If necessary, it is then possible to support development with physiotherapy or similar methods.
Due to the disorders in bone metabolism, the pediatrician should also regularly check the skeletal development.
Nutrition
As children get older, they develop an eating disorder with excessive food intake. It is then important to stick to a meal plan with a precisely defined calorie intake. Parents may need to strictly control access to food.
The eating disorder in PWS has a particularly serious effect on the course of the disease, as those affected do little exercise in addition to the increased calorie intake. As a result, severe obesity can easily develop with corresponding secondary diseases.
These sometimes limit the life expectancy of people with Prader-Willi syndrome. It is therefore crucial that affected children learn how to handle food properly with the help of their parents or caregivers from an early age.
Despite strict calorie restrictions, it is important that those affected are provided with sufficient vitamins and minerals through their diet. In Prader-Willi syndrome, bone metabolism disorders often occur. It may therefore be advisable to take vitamin D and calcium.
Growth and sex hormones
As with any therapy, side effects are also possible when taking growth hormones. These include water retention in the feet (foot oedema), a worsening of the curvature of the spine (scoliosis) or an increase in pressure in the skull. Breathing disorders sometimes occur at the beginning of therapy. During this time, it is important to monitor sleep.
In the case of puberty disorders, the symptoms can be alleviated with sex hormones. These are available as depot injections, hormone patches or gels. Under certain circumstances, the use of sex hormones can also improve behavioral problems. Oestrogens also support bone formation, but also have a number of side effects.
In principle, regular check-ups with the doctor are advisable during hormone therapy in order to check the success of the treatment and identify side effects at an early stage.
Psychological support
For adults affected, it may be necessary to adapt the living and working environment. In some cases, psychiatric abnormalities require medication. The aim of the intensive support is to achieve the best possible independence for those affected.
Surgical care
Surgery is sometimes necessary to alleviate certain symptoms of Prader-Willi syndrome. For example, children with Prader-Willi syndrome often suffer from a misalignment of the eyes. Strabismus in particular can be treated surgically to prevent visual impairment. Sometimes it is sufficient to temporarily cover the healthy eye.
Underdevelopment of the reproductive organs may also require surgery to move the testicles from the lower abdomen to the scrotum. Sometimes hormone treatment helps to enlarge the scrotum, allowing the testicles to descend.
In severe cases, an S-position of the spine (scoliosis) requires surgical correction.
Prevention
In addition, the course of the disease can be positively influenced by taking growth and sex hormones and regular check-ups with the relevant specialists.