October 26, 2024, 9:51 am | Read time: 8 minutes
Prader-Willi syndrome is a disorder caused by a rare genetic defect that affects a part of the diencephalon (hypothalamus). People born with the syndrome can be short, infertile, and have a lack of satiety – which can lead to the development of other dangerous diseases such as binge eating. They are also limited in their mental development.
A well-known symptom of the disease is pronounced muscle weakness, which can already be noticeable in a newborn baby. As a result, even drinking and swallowing problems can occur in infancy. Those affected by Prader-Willi syndrome also have to contend with conspicuous appearance and behavioral disorders. FITBOOK explains the causes and symptoms and how Prader-Willi syndrome progresses.
Overview
What is Prader-Willi syndrome?
Prader-Willi syndrome (known as “PWS” for short) is a rare disorder that leads to a developmental disorder of the nervous system. The cause is a genetic defect on a chromosome. This genetic change leads to important functions in the hypothalamus (part of the diencephalon) being suppressed, which has dangerous consequences for the person affected. The hypothalamus is responsible for regulating vital processes. These include blood pressure, water and salt balance, body temperature, food intake, and a person’s emotional behavior.1
In addition, various hormones are produced that either act directly on specific target organs (such as the thyroid gland and sex organs) or are responsible for the production of new hormones. The hormones produced in the hypothalamus are also able to influence a person’s growth.
Infants affected by this genetic defect often suffer from mental developmental delay, short stature, and low muscle tone. Additionally, obesity can develop in infancy due to a lack of satiety. This can lead to various secondary diseases.
Discovery of the disorder
Prader-Willi syndrome is a rare disorder that affects approximately one in 15,000 newborns. In 1965, Swiss pediatricians Andrea Prader, Heinrich Willi, and Alexis Labhart described the symptoms of the disorder for the first time.2
What are the causes?
Prader-Willi syndrome manifests as a dysfunction of the hypothalamus caused by a defect on a chromosome. More precisely, this is a missing section of chromosome 15. In healthy people, this gene section is present twice. In Prader-Willi syndrome patients, the gene segment is only present once, as it is missing on one of the two parental chromosomes.
The development of the disease has several causes:
Deletion of the chromosome segment of paternal origin
The term “deletion” refers to the absence of the paternal chromosome segment. At around 75 percent, it is probably the most common cause of Prader-Willi syndrome. Those affected are missing the paternal gene copy of chromosome segment 15.
Maternal disomy
Maternal disomy is the term used when individuals have two maternal chromosomes, which occurs in about 20 percent of cases.
Mutation in the imprinting center
In almost two percent of cases of Prader-Willi syndrome, the cause is a mutation in the imprinting center. In this case, both the maternal and paternal gene copies are present, but both gene copies are non-functional.
Angelman syndrome is also caused by a mutation on chromosome 15 but affects a different region of the chromosome.3
Is Prader-Willi syndrome hereditary?
As a rule, the risk of recurrence is low. Prader-Willi syndrome usually occurs after fertilization or during the development of the germ cells. However, it is also possible for the disease to be triggered by pre-existing genetic mutations. In this case, the risk of possible inheritance increases. Therefore, genetic counseling is recommended for parents who already have a child with Prader-Willi syndrome.4
These are the main characteristics of the disease
Little movement in the womb
The first symptoms of the condition can already become apparent during pregnancy. Children who suffer from Prader-Willi syndrome move very little. They also have a lower heart rate.
Lack of movement, low birth weight, and muscle weakness
Another abnormality occurs after birth: Not only do the babies have a conspicuous lack of movement, but they also suffer from low birth weight and muscle weakness. Most newborns have difficulty crying, sucking, or swallowing due to muscle weakness – and therefore struggle with complications when drinking. They are often underweight and can only gain weight slowly.5
External abnormalities
In addition to the aspects already mentioned, external abnormalities also occur in those affected. Characteristics of the disease are
- Long, narrow face
- Thin upper lip
- Almond-shaped eyes
- Mouth curved downwards
- Elongated skull (also known as “dolichocephaly”)
- Curvature of the spine (scoliosis)
- Osteoporosis (bone loss)
- The pigmentation of the hair and skin may also be slightly reduced
Visual disturbances
In addition, visual disturbances or strabismus of the eyes may develop.
Uncontrolled food intake
One of the functions of the hypothalamus is to control food intake. Due to the malfunction, those affected no longer feel full, which leads to uncontrolled and excessive food intake (hyperphagia). There is, therefore, no proper regulation of eating behavior. In the long term, this can lead to serious illnesses such as diabetes, obesity, cardiovascular disease, or even binge eating.
Disturbed pubertal development
The growth spurt typical of adolescents during puberty is also greatly reduced. Although puberty may start early, pubertal development often remains incomplete in those affected. Or features of physical development (e.g., pubic hair) may be completely absent.6
The disease can lead to underdevelopment of the sexual organs in boys and girls. Due to a lack of sex hormones and the limited function of sexual organs, infertility can be a possible consequence.
Impaired mental and psychological development
Prader-Willi syndrome is capable of affecting the mental and psychological development of the sufferer. The general delayed development of the affected child is also typical of the disease. For example, it can take almost twice as long to develop motor and language skills as it does in healthy children of the same age.
Those affected by the disorder have mild to moderate mental impairment. In addition, those affected often have learning and arithmetic difficulties.7
Abnormal emotional development
Children affected by Prader-Willi syndrome often exhibit abnormalities in their emotional development. A lack of impulse control, tantrums, or defiant, hostile behavior toward other children are just some of the symptoms that can occur. People who suffer from Prader-Willi syndrome are often very gifted in fine motor skills and attach great importance to rituals. They feel particularly secure when everything follows fixed structures. However, those affected by the disorder have difficulty understanding their own feelings and those of others – which can lead to conflicts when living together.
The symptoms worsen over time. In adulthood, however, it is possible for the symptoms to subside slightly. Almost ten percent of those affected develop psychoses. Forms of narcolepsy and epilepsy can also occur. Other symptoms include water retention, sleep disorders, and venous disorders. Breathing pauses or disturbances of the day-night rhythm or depressive phases can also be possible.
Progression of the disease
In principle, it is possible to lead a normal life with the disease. However, this depends on an early diagnosis: the earlier it is made, the more positive the impact on the long-term prognosis. Children’s quality of life, in particular, can be improved by parents controlling their eating habits, for example, and thus minimizing the risk of obesity.
Probably the most dangerous health risk is increasing obesity and the associated complications that can occur. Normal life expectancy can be reduced due to severe obesity and cardiovascular problems. Even though many people affected by Prader-Willi syndrome can be independent to a certain extent, it is not enough to lead an independent life without care.
Diagnosis of Prader-Willi syndrome
An initial examination of newborns who show persistent or unexplained weakness can determine whether Prader-Willi syndrome is present. There are two methods of diagnosing the condition:
Physical examination
One of the most noticeable symptoms of the disease is pronounced muscle weakness. This can be noticeable, for example, if the infant has problems drinking and swallowing. At the same time, the outward appearance of the person can also indicate whether Prader-Willi syndrome is present.
In adults or older children, a blood test can help detect a deficiency in growth hormone if the disease is present. However, the concentration of female sex hormones (such as estrogen) is also sometimes reduced due to the underdevelopment of the sexual organs. By examining brain waves using an electroencephalogram (EEG), abnormalities can also be detected in those affected.
Genetic testing
Genetic testing can confirm a suspected case of Prader-Willi syndrome and rule out other diseases.
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Treatment of Prader-Willi syndrome
Prader-Willi syndrome cannot be cured. Treatment aims to improve the symptoms of the disease as much as possible. This includes hormone replacement therapy, controlling food intake, and dealing with behavioral problems through psychological support. It is also advisable to have the motor activity of those affected examined regularly. Physiotherapy can also be helpful in alleviating physical symptoms. In rare cases, surgical interventions are necessary to provide relief. However, the exact therapeutic measures should be individually tailored to the person affected and must be discussed with the responsible doctor.