Prader-Willi Syndrome
Clemens Gödel is a freelancer for the medical team.
More about the experts All content is checked by medical journalists.The Prader-Willi syndrome (PWS) is the result of a congenital defect in the genetic material. Affected infants are short, mentally underdeveloped and muscular. In early childhood, they develop an insatiable hunger that leads to pronounced obesity. The resulting secondary diseases are to be treated by means of therapy from various medical specialties. Read more about the symptoms, diagnosis and therapy of Prader-Willi syndrome here!
ICD codes for this disease: ICD codes are internationally recognized codes for medical diagnoses. They can be found, for example, in doctor's letters or on certificates of incapacity for work. Q87
Prader-Willi syndrome: description
The Prader-Willi-Syndrome (wrongly also Willi-Prader-Syndrome) was described for the first time in 1956 by the paediatricians Andrea Prader, Alexis Labhart and Heinrich Willi. About one in 20,000 newborns suffers from Prader-Willi syndrome. The cause is a genetically triggered dysfunction of the hypothalamus, an important switching center in the brain. The manifestation of the Prader-Willi syndrome can be very different and complex.
Prader-Willi syndrome: symptoms
Affected fetuses are noticed even before birth. They move noticeably little in the womb. The heart rate is lower than normal. At the time of birth, fetuses with Prader-Willi syndrome are more likely to be in abnormal positions in the mother's body. Babies need a lot of support during and after birth.
Immediately after birth, affected newborns stand out due to a sedentary lifestyle, (muscle) weakness and a low birth weight. The typical screaming after the birth may also be absent or only weak. Due to the pronounced weakness and the resulting sucking and swallowing disorders, the babies find it difficult to drink.
Babies with Prader-Willi syndrome often show certain external characteristics. The narrow face is characterized by almond-shaped eyes and a small mouth with a thin upper lip. The skull is often long (dolidochocephaly), and the hands and feet are small. The spine can be bent into an S-shape (scoliosis). The bone substance in the whole body shows damage and defects (osteoporosis / osteopenia) in the X-ray image. The pigmentation of the skin, hair and retina may be reduced. Visual disturbances and squint positions (strabismus) of the eyes are also possible. The scrotum is small and often empty (undescended testicles). Overall, the development of the sick children is delayed.
At the end of the first year of life, the muscle weakness improves somewhat. However, there is always at least a mild weakness. Normal activities can quickly become tiring and strenuous for patients with Prader-Willi syndrome. Even so, children enjoy typical childhood activities just as much. Growth is significantly reduced in toddler age.
Uninhibited food intake
As the disease progresses, affected children eat more and more (hyperphagia) - without feeling full. Food is hoarded and, even in severe cases, stolen. It is extremely difficult for children to control their eating habits. Therefore they develop a distinct obesity (obesity). They gain weight particularly quickly because there is a marked discrepancy between the high calorie intake and the low energy consumption.
Being overweight has typical secondary diseases: the heart and lungs suffer from the stress of obesity. A quarter of all those affected developed diabetes mellitus by the age of 20. Sleep disorders, venous diseases (thrombophlebitis) and water retention are also among the multitude of possible consequences. In the course of the disease, sleep disturbances can occur. In addition to repeated pauses in breathing, disturbances of the day-night rhythm or deep sleep are possible. Affected children find learning difficult.
The development of puberty is disturbed
The typical growth spurt during puberty is small. Affected children usually do not grow taller than 140 to 160 centimeters. Although puberty can begin prematurely (premature adrenarche), in many cases the development of puberty never ends. Those affected usually remain sterile. In boys, the penis and especially the testicles remain small. There is no pigmentation and wrinkles on the scrotum. There may be no voice breaking. In girls, the labia and clitoris remain underdeveloped. The first menstrual bleeding does not occur at all, prematurely or late, sometimes only between the ages of 30 and 40.
Psychological and spiritual development
Both mental and psychomotor development are disturbed in Prader-Willi syndrome. Milestones in child development are often reached later than in healthy peers. Linguistic and motoric development sometimes take twice as long as in healthy peers.
The average intelligence quotient (IQ) is between 60 and 70 and thus well below the norm. The physical weakness can make speaking difficult. Speech development is delayed and speech understanding is impaired, depending on the low IQ. Around 40 percent of the sick are on the verge of intellectual disability. Independent of the IQ, learning disorders such as arithmetic difficulties also appear. School performance is mostly below average.
Both the development of emotions and the behavior can be noticeable. Affected people are sometimes described as stubborn and quick-tempered. Psychiatric abnormalities can occur even in early childhood: forms of so-called opposition behavior as well as rigid and possessive behavior are described. Routine processes can be difficult. Sometimes processes have to be repeated compulsively. Autistic traits occur in around 25 percent of patients. Attention Deficit Disorder (ADD) is also common.
The symptoms usually increase with age and overweight. In older adults, however, the Prader-Willi syndrome symptoms can easily regress. Around ten percent suffer from psychosis. In addition, epilepsies and forms of "sleep addiction" (narcolepsy) are associated with Prader-Willi syndrome.
Prader-Willi syndrome: causes and risk factors
The cause of Prader-Willi syndrome is believed to be a dysfunction of part of the midbrain known as the hypothalamus. Among other things, this results in a deficiency in the important growth hormone. The disorder is caused in around three quarters of cases by the lack of a gene segment on chromosome 15 (15q11-q13). In Prader-Willi syndrome, a defect in the paternal chromosome copy seems to be of particular importance (70 to 75 Percent) so that there is only one copy of the gene. Another possibility is that both genes of the double set of chromosomes only come from the mother (uniparental disomy, 25 to 30 percent). A so-called “imprinting defect” is less common (one percent). The term “imprinting” describes the fact that genes are read depending on their origin (on the maternal or paternal side).
In most cases, the disorder is not inheritable. It usually only develops during germ cell development or after fertilization. On the other hand, however, it is possible that existing gene mutations (mostly so-called balanced translocations) also cause Prader-Willi syndrome. In these cases the risk of inheritance is increased.
Prader-Willi Syndrome: Investigations and Diagnosis
All newborns with persistent and unexplained weakness should be tested for the PWS. Even the neonatal doctor (neonatologist) or pediatrician (pediatrician) will suspect Prader-Willi syndrome after the birth due to the behavior of the child. No so-called predictive tests are carried out without evidence of the presence of this syndrome. However, it is entirely possible to diagnose Prader-Willi syndrome even before birth.
Physical and technical examinations
In most cases, the physical examination already gives a high level of suspicion of Prader-Willi syndrome (Holms Criteria 1993, 2001). The main characteristic of Prader-Willi syndrome is pronounced weakness, which is particularly evident when drinking. The appearance also gives clues. Normally detectable reflexes are only weakly pronounced.
A measurable deficiency of growth hormone in the blood is also diagnostically helpful. Sex hormones (estrogen, testosterone, FSH, LH) are also mostly reduced in those affected. This is accompanied by an underdevelopment of the sexual organs. The function of the adrenal cortex is disturbed in many cases. The formation of sex hormones (androgens) can also start prematurely (early adrenarche).
The examination of the brain waves (electroencephalogram, EEG) can also be suspicious.
Genetic examination
Genetic tests are performed to confirm the suspicion of Prader-Willi syndrome. In the first step, the methylation of the crucial point on chromosome 15 (15q11.2-q13, "SNRPN locus") is examined. Enzymes can bind so-called methyl groups to the DNA and thereby modify it. In over 99 percent of cases, this examination provides the diagnosis. Otherwise, another common method for detecting chromosome changes, fluorescence in situ hybridization (FISH), is carried out.
Similar diseases are Martin Bell Syndrome or Angelmann Syndrome. The disorder in Martin Bell Syndrome is on the X chromosome (fragile X syndrome). In Angelmann syndrome and Prader-Willi syndrome, the same position on chromosome 15 is deleted in most cases - but in Angelmann syndrome only the one on the maternal chromosome.
Prader-Willi Syndrome: Treatment
There is no cure for Prader-Willi syndrome. However, with the help of strictly guided, supportive therapy, the symptoms can be alleviated. The main components of treatment are food control, hormone replacement therapy, and treatment of the behavioral problems.
nourishment
Adequate nutrition and sufficient growth must be ensured, especially if the muscle weakness is severe. Probes or special artificial nipples can be used to facilitate the intake of food. In addition, a feeding plan with a well-documented calorie intake and weight control should be drawn up.
However, as children get older, they develop an overeating disorder. Then a plan with a strict calorie restriction must be followed. A fat restriction is not always aimed for, as fat is important for horn development. The eating disorder may require strict food access management. The eating disorder in Prader-Willi syndrome has a particularly serious effect on the course of the disease, since those affected move little and there is thus a large discrepancy between calorie intake and requirement. It is crucial to involve the parents intensively and to offer the sick child a solid structure.
At the same time, it must be ensured that enough vitamins and minerals are supplied.In the Prader-Willi syndrome, disorders of the bone metabolism often occur, which can be prevented with vitamin D and calcium intake. Skeletal development, especially the spine, should be monitored regularly.
The activity and motor development of the sick child are regularly examined and, if necessary, supported therapeutically with physiotherapy or similar methods.
Growth hormone
From the age of two, the growth hormone HGH can also be given as a drug. This therapy should be stopped when the growth plates in the bone are closed (X-ray control). Hormone therapy should always be closely monitored. The hormone administration has a positive effect on body development, but side effects are foot edema, worsening of the curvature of the spine (scoliosis) or an increase in pressure in the skull (pseudotumor cerebri). Breathing disorders can occur at the start of therapy. It is therefore important to monitor sleep at the start of therapy. Monitoring HGH hormone therapy also includes regular measurements of thyroid levels and blood levels of the growth factor IGF-1.
In the case of puberty disorders, sex hormones can be administered as depot injections, hormone patches or gel. This can improve the behavioral problems. Estrogens also help build bones, but they also have a number of side effects.
Psychological support
The affected child should receive help to support behavior development and the achievement of developmental milestones. Social skills in particular have to be trained in Prader-Willi syndrome. Interaction with peers and caregivers should also be encouraged. One-on-one supervision may be necessary at school. If necessary, the living and working environment must be adapted. Psychiatric abnormalities may require drug therapy, for example with a serotonin antagonist. The aim of the intensive support is the best possible independence.
Surgical supplies
Any cleft lip and palate that may already exist at birth can be treated by surgeons at an early stage. Misalignments of the eyes, especially squint positions, can also be treated surgically to prevent visual disturbances. First of all, temporarily covering the healthy eye can help.
The underdevelopment of the genital organs may require surgery to move the testicle from the lower abdomen into the scrotum. Beta-hCG (human chorionic gonadotropin) can enlarge the scrotum and allow the testicle to sink.
Skeletal changes in the Prader-Willi syndrome can also be treated surgically. An S-position of the spine (scoliosis) requires surgical correction in severe cases, but is usually treated without surgery (for example with a corset.
Prader-Willi syndrome: disease course and prognosis
The earliest possible diagnosis of “Prader-Willi Syndrome” can have a positive effect on the long-term prognosis. A positive influence on (eating) behavior and the eventual administration of growth hormones can improve the quality of life of the affected child.
Eating behavior, weight and growth should be checked at regular intervals after the diagnosis. Development, function, behavior as well as psychiatric abnormalities are checked. Close observation and care by a specialist who can coordinate and ensure interdisciplinary care is very important.
Sick people have an increased risk of repeatedly contracting infections. Special care must be taken during operations: After anesthesia, the wake-up phase often takes longer and there is an increased risk of breathing disorders.
The biggest problem, however, is increasing obesity. In the course of life, the resulting complications predominate. The mortality is also increased due to the complications. The increased mortality in Prader-Willi syndrome is therefore primarily due to heart, vascular or lung diseases.
The inheritance risk is low. In most cases, the genetic change is spontaneous and not inherited. The risk for parents of having a second child with Prader-Willi syndrome is low. Those affected often remain childless.
Only in rare cases is the Prader-Willi syndrome caused by changes in the genetic information in the parental chromosome set, which are inheritable and also lead to a higher probability of inheritance. If a child has Prader-Willi syndrome, we recommend that parents who wish to have children seek advice from human geneticists.
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