Prader Willi Syndrome: Symptoms, Causes, Diagnosis, Treatment, Prevention and Prediction

SPW is a genetic disorder that occurs because of the loss of function of specific genes.

Beginning in childhood, a person constantly suffers from hunger, which often leads to obesity and type 2 diabetes.

There is also an intellectual deterioration that ranges from mild to moderate and behavioral problems.

About 70% of cases occur when part of the father’s chromosome 15 is removed.

In another 25% of cases, the person has two copies of chromosome 15 from his mother and none from his father.

As parts of the mother’s chromosome go out, they end up without copies of certain genes.

SPW is not usually inherited, but genetic changes occur during the formation of the ovum, sperm or early development.

There are no known risk factors. Those who have a child with Prader Willi Syndrome have less than a 1% chance that the next child will inherit this genetic condition.

Prader-Willi syndrome has no cure and affects 1 in 30,000 people.

Both men and women are affected equally. The condition is named after Andrea Prader, Heinrich Willi and Alexis Labhart, who described it in detail in 1956.

An earlier description occurred in 1887 by John Langdon Down.

Signs and symptoms

There are many recognized signs and symptoms of Prader-Willi syndrome.

Symptoms can range from poor muscle tone to behavioral problems during childhood.

Some symptoms that are usually found more easily in babies, in addition to poor muscle tone, would be the lack of visual coordination; some are born with almond-shaped eyes; and due to poor muscle tone, the baby may not have a strong sucking reflex.

Their cry is weak, and they have difficulty waking up. Another sign of this condition is a thin upper lip.

More aspects seen in a clinical description include hypotonia and abnormal neurological function, hypogonadism , cognitive and developmental delays, hyperphagia and obesity , short stature and behavioral and psychiatric disorders.

Holm and Al. (1993) describe the following characteristics and signs as SPW test indicators, although not all will be present at the same time.

Uterus and birth

  • Reduced fetal movement.
  • Frequent abnormal fetal position.
  • Excess of amniotic fluid
  • Lethargy.
  • Hypotonia .
  • Feeding difficulties (due to poor muscle tone that affects the suction reflex).
  • Difficulty breathing
  • Hipogonadismo.

Childhood

  • Intellectual delay
  • Sleeping excessively
  • Strabismus (crossed eyes).
  • Scoliosis (often not detected at birth)
  • Cryptorchidism .
  • Speech retardation
  • Poor physical coordination
  • Hyperphagia: (overeating) begins between 2 and 8 years, and continues into adulthood.
  • Over weight.
  • Sleep disorders.
  • Delayed puberty.
  • Short stature.
  • Obesity.
  • Extreme flexibility.

Adulthood

  • Infertility (men and women).
  • Hipogonadismo.
  • Scarce pubic hair.
  • Obesity.
  • Hypotonia (low muscle tone)
  • Learning disabilities (in some cases average intelligence).
  • High predisposition to diabetes mellitus.

Physical appearance

  • Prominent nasal bridge.
  • Small hands and feet with sharp fingers.
  • Soft skin, which bruises easily.
  • Excess fat, especially in the central part of the body.
  • High and narrow front.
  • Thin upper lip.
  • Mouth down.
  • Almond eyes.
  • Clear skin and hair in relation to other members of the family.
  • Lack of complete sexual development.
  • Stretch marks.
  • Delayed motor development.

Causes

Prader-Willi syndrome is a genetic disorder caused by an error in one or more genes.

Although the exact mechanisms responsible for Prader-Willi syndrome have not been identified, the problem lies in genes located in a particular region of chromosome 15.

With the exception of genes related to sexual characteristics, all genes are presented in pairs: a copy inherited from their father and a copy inherited from their mother.

For most types of genes, if one copy is “active” or manifests itself, then the other copy will do so, although it is normal for some types of genes to act alone.

Prader-Willi syndrome occurs because certain paternal genes that must be expressed do not do so for one of these reasons:

  • The paternal genes on chromosome 15 are missing.
  • The child inherited two copies of chromosome 15 from the mother and not one from the father and another from the mother.
  • There is some failure or error in the paternal genes on chromosome 15.

In this syndrome, an irregularity in chromosome 15 interrupts the normal functions of a portion of the brain called the hypothalamus , which controls the release of hormones to our body.

If the hypothalamus does not work properly it can cause the obstruction of processes that cause problems of sexual development, growth, hunger, body temperature, sleep and mood.

Determining which genetic defect caused Prader-Willi syndrome may be useful for genetic counseling.

Heritage:

Most cases of Prader-Willi syndrome (PWS) are not inherited and are due to random events during the formation of ovules or sperm, or early fetal development.

This is usually the case when the syndrome is caused by a maternal uniparental disomy or by a deletion in the father’s chromosome 15.

However, in rare cases, a genetic change responsible for SPW can be inherited.

The risk to family members of a person with PWS depends on the genetic cause of the condition in the affected person.

Because the various genetic causes of PWS are complex, people seeking information about specific risks for themselves or their family members are encouraged to speak with a genetic professional.

Diagnosis

The diagnosis of suspected Prader-Willi syndrome (PWS) is usually made by a doctor based on clinical symptoms.

SPW should be suspected in any child born with significant hypotonia (muscle weakness). The diagnosis is confirmed by a blood test.

The preferred test method is a “methylation analysis” that detects 99% of cases, including all major genetic subtypes of SPW (deletion, uniparental disomy or imprinting mutation).

A “FISH” test (Fluorescent In Situ Hybridization) will identify those patients with PWS due to a deletion, but will not identify those who have Prader-Willi syndrome due to “UPD” (uniparental disomy) or a printing error.

Almost all cases of PWS can be confirmed with one of the previous tests.

However, in the rare case that laboratory tests do not confirm SPW, a clinical diagnosis may be useful for the development of a management plan for this syndrome.

Treatment

The treatment of PWS is currently based on the treatment of the symptoms of the disorder as they arise.

Growth hormone deficiency is present in almost all children and in many adults with PWS.

In multiple studies, it has been discovered that human growth hormone (HGH) is beneficial for people with Prader-Willi syndrome.

In June 2000, HGH was officially approved by the Federal Drug Administration (FDA) in the United States for use in patients with Prader-Willi syndrome.

HGH is effective not only to increase height, but also to decrease body fat, increase muscle mass, improve weight distribution, increase strength and bone mineral density.

In addition, studies suggest its positive effects on development and behavior.

In 2013, guidelines for the use of HGH in SPW were developed as part of an international meeting of experts.

Despite treatment with HGH, many challenging symptoms associated with PWS are still difficult to treat.

The inability to control food intake is often the biggest obstacle for people with PWS to live independently.

To date, no medication has proven effective in regulating appetite in SPW, and therefore, strict environmental control and constant monitoring are the only ways to prevent overweight and extreme obesity that threaten the life of a patient. with SPW today.

However, there are a number of new anti-obesity drugs in clinical development, some of which may benefit the SPW population, and the evaluation of these drugs in clinical trials is an important priority for FPWR.

Meanwhile, a well-balanced diet is recommended along with careful control of the environment to minimize uncontrolled access to food.

Additional challenges in PWS include sleep disturbances, hormonal abnormalities, scoliosis, dental problems and skin bites.

Breathing problems during sleep are common and periodic sleep studies are suggested for all ages, including infants.

Excessive daytime sleepiness can be improved with the medication that stimulates wakefulness, modafinil.

This medication also improves cognitive performance and decreases appetite in typical individuals.

The common hormonal abnormalities in PWS (low thyroid hormones, testosterone, estrogen, etc.) can be treated by an endocrinologist with standard medications.

The scoliosis is also very common in PWS and should be treated by an orthopedic doctor familiar with this syndrome.

Skin flares are common in those with PWS, and can be helped with the use of N-acetylcysteine.

Finally, the management and treatment of psychiatric and behavioral problems associated with PWS can also be very challenging.

A combination of behavioral therapy, environmental control, and medication may be needed.

It is recommended to consult with mental health professionals familiar with Prader Willi Syndrome.

Prevention

If you already have a child with this condition and would like to have another baby, it is best to seek genetic counseling.

A genetic counselor can help determine your risk of having another child with Prader-Willi syndrome.

Forecast

Children with Prader-Willi syndrome can be integrated into the classroom setting, although they need additional speech therapy and should have additional periods of physical activity instead of rest periods.

In general, they need a structured environment and may need a smaller class for individual attention.

People with PWS usually reach adulthood and can function in a group home setting, doing vocational work or attending classes at community colleges.

According to the Prader-Willi Syndrome Association, people with the syndrome can hope to achieve many of the things their peers do.

However, they do need a significant amount of support from their families and from school, work and residential service providers.

Even those with IQ in the normal range need dietary supervision throughout life and protection against food availability.

Complications that could affect quality of life and potentially shorten life expectancy include those related to hypogonadism, behavioral or psychological problems and morbid obesity.