Prader-Willi syndrome in children: causes and symptoms of the disease

Prader-Willi syndrome is a rare genetic disorder that causes a wide range of physical symptoms, learning difficulties and behavioral problems. The disease can usually be noticed soon after birth.

Symptoms of Prader-Willi syndrome

Prader-Willi syndrome can cause a wide range of symptoms and affect a child's physical, psychological and behavioral development.

Lethargy

Fatigue caused by muscle weakness usually occurs soon after birth and is medically known as hypotonia. With it, the child may not have a full range of movement, cry less, suck incorrectly, and also lose weight before one year.

Poor sexual development

Boys may have an abnormally small penis, or one or both testicles may still be inside their abdomen (undescended testicles). Little girls will also have underdeveloped genitals.

Children with Prader-Willi syndrome experience puberty later than usual and may not go through full development into adulthood. For example: boys may have a high-pitched voice and little facial and body hair. Girls often don't start menstruating until they're 30, and their breasts remain underdeveloped. When periods do occur, they are usually irregular and very light.

It is almost unknown whether men or women with Prader-Willi syndrome have children. People with this condition are usually infertile due to underdeveloped testicles and ovaries. However, sexual activity is usually possible.

Distinctive external features

Children with Prader-Willi syndrome have several distinctive features, including:

almond-shaped eyes;
strabismus;
narrow forehead;
at the temples there is a narrow bridge of the nose;
thin upper lip and downturned mouth;
unusually light hair, skin and eyes;
small hands and feet.

These features are usually noticeable immediately after birth.

Increased appetite

Children with Prader-Willi syndrome have an increased appetite, a condition called hyperphagia.

Between the ages of 1 and 4 years, the child begins to show increased interest in food, ask for extra food and misbehave in order to get more. This behavior increases during childhood and is observed in all patients with Prader-Willi syndrome.

Behaviors may include:

tantrums and aggression to get food;
interest in pictures of food, food-related games, or discussions of food;
food theft;
eating unsuitable foods, frozen or raw foods, or food waste.

Children with Prader-Willi syndrome can tolerate much larger amounts of food before the body automatically vomits it back, and they are not as sensitive to pain. Therefore, patients can even eat things that a person would not normally consider as food. Because of this, children with Prader-Willi syndrome are at increased risk of:

food poisoning;
strangulation;
stomach rupture.

Vomiting and abdominal pain are the two most common signs of gastric rupture.

Children with Prader-Willi syndrome do not always become obese and can remain slim if diet and nutritional issues are controlled. Such patients will never learn to control their food intake themselves. They also have a slow metabolism, and require less food and calories than their peers.

Decreased muscle tone means they are less physically active and do not burn as much energy as others.

Learning difficulties and developmental delays

Most children with Prader-Willi syndrome have mild to moderate learning difficulties and low IQs. This means it will take longer for your child to reach important developmental milestones. For example, children with Prader-Willi syndrome typically begin sitting at about 12 months and walking at about 24 months. Many people start speaking later and have difficulty pronouncing some sounds.

Most children with Prader-Willi syndrome can attend regular school with additional support, although some may require specialized schooling.

Patients are distinguished by weak short-term memory, which cannot be said about long-term memory. Despite these problems, children with Prader-Willi syndrome tend to be good at solving puzzles such as word searches.

Short stature

Children with Prader-Willi syndrome are usually much shorter than their peers. This usually becomes obvious by the time they are 2 years old.

Low levels of human growth hormone (hCG) promote short stature, and children will not go through the typical growth spurt during puberty. If the hCG is not replaced, the average adult height for people with Prader-Willi syndrome is 159 cm for men and 149 cm for women.

Children may be prescribed an artificial version of growth hormone to stimulate growth.

Behavioral problems

Most children with Prader-Willi syndrome have difficult behaviors such as tantrums and stubbornness. Typical behavioral problems include:

short temper and sudden attacks of rage, which can be triggered by minor events;
stubbornness and tendency to argue;
behavior manipulation;
asking the same question over and over again or returning to the same topic in conversation;
repeating the same action (for example, playing the same game or watching the same video over and over again);
keeping a very strict daily routine - any unexpected disruption to the routine can throw the child off balance.

Although these behavioral problems can be challenging for parents, children with Prader-Willi syndrome also have many positive aspects to their personality, such as gentleness, kindness, caring, and a cheerful disposition.

Skin picking

Four out of five children with Prader-Willi syndrome are obsessed with skin. They may scratch, puncture or pull at the face or hands, sometimes using paper clips or tweezers. This can lead to open sores, scarring and infection.

Sleep disturbance

Many children with Prader-Willi syndrome have problems sleeping. They may be tired and sleep during the day, but then wake up at night or very early in the morning. Some children have interrupted breathing during sleep (sleep apnea).

These episodes cause excessive sleepiness during the day, which only worsens physical inactivity and obesity.

Sleep apnea gets worse as the child gains weight.

High tolerance to pain and vomiting

Children with Prader-Willi syndrome have a high tolerance to pain, which can be potentially dangerous. For example, a serious condition such as appendicitis causes severe pain in most people, but may go unnoticed in a child with Prader-Willi syndrome. Therefore, if a child does complain of pain, it should be taken seriously.

Abnormal curvature of the spine

Poor muscle tone means an increased likelihood of developing a curvature of the spine (scoliosis).

Other diseases

Children with Prader-Willi syndrome may develop:

vision problems - myopia or farsightedness, strabismus;
poor muscle tone in the intestines, which can cause constipation or bloating;
caries due to a small amount of saliva;
weakening of bones (osteoporosis).

Causes of Prader-Willi syndrome

Prader-Willi syndrome is caused by a genetic defect on chromosome 15. Genes contain the instructions for creating a person. They are made of DNA and are packaged in strands called chromosomes. A person has 2 copies of all his genes, which means that the chromosomes are divided in pairs.

Humans have 46 chromosomes (23 pairs). One of the chromosomes, belonging to pair No. 15, is abnormal in Prader-Willi syndrome. About 70% of cases of Prader-Willi syndrome result from missing genetic information from the copy of chromosome 15 inherited from the father. This defect is called "paternal ablation". Paternal ablation is thought to be completely random, so it is virtually impossible to have more than one child with Prader-Willi syndrome caused by paternal ablation.

However, if the condition is caused by another type of problem with chromosome 15, there is a very small chance that the parents may have another child with the syndrome.

The defect in chromosome 15 is thought to disrupt the normal development and functioning of a part of the brain called the hypothalamus. It plays an important role in many body functions, such as producing hormones and helping regulate appetite. Problems with the hypothalamus may explain some of the typical features of Prader-Willi syndrome, such as slow growth and constant hunger.

Studies using advanced brain imaging technology have shown that after eating, people with Prader-Willi syndrome have very high levels of electrical activity in a part of the brain known as the frontal cortex. It is associated with physical pleasure and a feeling of satisfaction. It is possible that people with Prader-Willi syndrome find the act of eating extremely rewarding and enjoyable and constantly seek out food to achieve this pleasure.

Another theory is that in Prader-Willi syndrome, the hypothalamus cannot judge the level of food in the body as well as normal. This means that a person with the disease always feels hungry, no matter how much food they eat.

Establishing diagnosis

A definitive diagnosis of Prader-Willi syndrome can usually be made through a series of genetic tests.

Genetic testing

Genetic testing can be used to check the chromosomes in a child's blood sample for abnormalities known to cause Prader-Willi syndrome. In addition to confirming the diagnosis, the results should also help determine the likelihood of having another child with the syndrome.

Checklist for diagnosing Prader-Willi syndrome

A checklist of symptoms known to be typical of Prader-Willi syndrome is also used to determine which children should be tested. This checklist may also be helpful to parents who are concerned about their child's development, behavior and eating habits, or to those who want to know whether their child may have Prader-Willi syndrome.

Basic criteria (one point is scored for each of the following symptoms the child has):

flaccidity and weakness of muscles that appear during or shortly after birth;
feeding problems and failure to grow during the first year of life;
rapid weight gain between 1 and 6 years of age;
characteristic facial features such as almond-shaped eyes and thin upper lips;
insufficient activity of the testicles or ovaries (hypogonadism), leading to delayed sexual development;
delayed physical development or learning difficulties.

Minor criteria (and each of the following symptoms counts half a point):

lack of movement during pregnancy, such as kicking your legs in the womb, or an unusual lack of energy after birth;
sleep disorders such as apnea;
delayed or absent puberty;
unusually light hair, skin and eyes;
narrow hands;
thick and sticky saliva;
strabismus or farsightedness;
problems with correct pronunciation of words and sounds;
picking at the skin.

Total score:

If a child is under 3 years old and scores 5 points, including at least 3 points from the main criteria, we may be talking about Prader-Willi syndrome - in this case, genetic testing is recommended.
If the child is over 3 years old and scores 8 points, of which at least 4 points are from the main criteria, we can also talk about Prader-Willi syndrome - in this case genetic testing is also recommended.

There is no cure for Prader-Willi syndrome, but your child may receive medical support to help them cope.

Treatment of diseases in children

Poor nutrition

Babies with Prader-Willi syndrome have difficulty feeding at birth and may need to be fed through a tube that goes up the nose and down the throat into the stomach. After a few months, you can usually feed your baby normally using breast milk or bottle milk.

Dietitians and speech therapists can help with advice on what formula to give and how to encourage your baby to feed.

Undescended testicle (cryptorchidism)

For cryptorchidism in boys, surgical intervention is recommended to help correct this feature in the first or second year of life. Treatment is recommended because:

a boy may have an increased risk of developing testicular cancer;
The child may have problems with self-esteem.

Weight and Diet Management

The most important aspect of caring for a child with Prader-Willi syndrome is trying to manage his diet and prevent him from gaining too much weight. Your baby will never learn to control his food intake on his own, so you need to do it for him.

Nutrition tips:

Instill good habits with a healthy diet and regular meals as soon as your baby starts eating solids - don't wait until he shows signs of increased appetite;
do not give your child sweets and high-calorie foods;
provide smaller portions of carbohydrates such as potatoes, rice or pasta;
increase the amount of low-calorie foods such as vegetables, salads and fruits.

The child will not learn to control his food intake on his own, and you need to take control of everything:

Make sure your child eats regularly.
Cut off access to food outside of meal times. You may need to lock cabinets or the refrigerator.
Make sure your child cannot get food from trash cans or the freezer.
Keep food out of your child's sight.

Various medications can be used to suppress appetite, but studies have shown that all of these drugs are ineffective.

Weight loss surgery is not recommended for children with Prader-Willi syndrome because they do not have the willpower to adhere to the strict diet required after surgery.

Exercise plays an important role in maintaining a healthy weight. Children should get at least 60 minutes of exercise per day.

Many children with Prader-Willi syndrome have low energy levels, so exercise should be broken up into 5-10 minute sessions throughout the day.

Children with Prader-Willi syndrome usually prefer individual activities to team sports, such as swimming, walking, and training in the gym.

It is important not to promise food as a reward to encourage your child to participate in exercise because this may promote unhealthy behavior.

Hormone therapy

Treatment with an artificial version of human growth hormone (hCG) is usually recommended for children with Prader-Willi syndrome. HCG also has a number of other important health benefits. For example:

increases muscle size while reducing body fat;
increases muscle strength, which helps with developmental progress such as walking and running;
Helps normalize facial appearance, making the distinctive facial features associated with Prader-Willi syndrome less noticeable.

It is generally recommended that growth hormone treatment be started in early childhood, between 6 months and 2 years of age.

Before you start taking it, a test to check for breathing problems (sleep study) is usually done.

Managing Behavioral Problems

Most children with Prader-Willi syndrome do best if they have a very structured environment and routine.

Tips for parents:

Establish a regular daily routine and communicate planned changes promptly.
Don't rush your child.
Make sure that other people, relatives and teachers, are informed about how to interact with the child.
Avoid eating in front of your child to prevent him from thinking about food.

Parents often learn to recognize the warning signs of a tantrum. Sometimes you can stop a tantrum before it starts by using several approaches.

For example:

try to divert attention from the situation by doing or saying something unexpected, or by talking about a subject that interests the child;
Invite your child to go to a quiet place for a few minutes and take a few deep breaths or listen to soothing music;
Avoid saying things like “you better not throw a tantrum about this”;
After a tantrum, try to remain as calm as possible.

Eating

Many children with Prader-Willi syndrome will try to eat if given the opportunity. This is not because they are naughty, but because they are unable to control their impulses when it comes to food. However, eating is a behavioral issue that must be addressed or the child may become obese.

For younger children, a verbal agreement such as “if you stick to your diet, you can play extra hours with your puzzles” is sufficient.

In older children and adolescents, a written contract may be more appropriate, especially if children with Prader-Willi syndrome respond well to clear instructions.

Most children with the syndrome will automatically lie about eating, even if the evidence is overwhelming. So instead of asking, "Did you steal that food?", say something like, "I know what you ate, and we need to talk about why it's wrong."

It is important that the child understands the consequences of his actions and what is considered acceptable behavior. If they steal food or money to buy it, always insist that they apologize and return the money.

Skin care

Frequently picking at the skin can lead to scarring and skin infections such as cellulitis, an infection of the underlying tissue. It is very important that cellulitis is detected early and treated with high doses of antibiotics.

It is recommended that your child's nails be kept as short as possible. This should help minimize skin damage.

Try to keep any affected body part covered.

Keep all areas of damaged skin as clean as possible. If your child has a history of frequent skin infections, he or she may be prescribed an antibacterial cream.

Two types of treatment that are moderately effective in preventing skin problems are cognitive behavioral therapy (CBT) and medication.

Cognitive behavioral therapy CBT is a type of talk therapy. It aims to change unhelpful and unhealthy behavior patterns by changing the way people think. People with Prader-Willi syndrome are thought to choose the skin as a way to cope with situations such as feelings of unhappiness or boredom. CBT can help people cope with these situations.
Medication type. A type of antidepressant—selective serotonin reuptake inhibitors (SSRIs) or antipsychotics (medicines commonly used to treat psychosis)—is sometimes recommended to treat Prader-Willi syndrome. However, these drugs may cause side effects and are usually not recommended for children under 18 years of age. Drug treatment is usually only considered if the symptoms of the skin lesion are severe enough to justify the associated risks of treatment.

Treatment of psychosis

A small number of people with Prader-Willi syndrome develop psychosis, usually in adolescence or adulthood.

Psychosis is a mental health problem that causes people to perceive or interpret things differently than those around them. Symptoms of psychosis usually begin suddenly and cause a person to act in ways that are uncharacteristic.

Psychosis can be treated with CBT or medications such as antipsychotics.

Adults with Prader-Willi syndrome

Most adults with Prader-Willi syndrome are unable to live fully independent lives, such as in their own home and have a regular job, due to behavioral and eating problems. However, they can lead an active social life and participate in volunteering. Adults with the syndrome who do not live with their parents are likely to require residential care.

Long-term problems caused by Prader-Willi syndrome

Prader-Willi syndrome in itself is not life-threatening. However, binge eating and weight gain can cause young people with the disease to develop obesity-related conditions such as:

diabetes mellitus type 2;
heart failure;
difficulty breathing.

Reference - nhs.uk/conditions/prader-willi-syndrome/living-with/

Genetics [edit]

PWS is associated with an epigenetic phenomenon known as imprinting. Typically, the fetus inherits an imprinted maternal copy of PW genes and a functional paternal copy of PW genes. Because of imprinting, the maternally inherited copies of these genes have little function, and so the fetus relies on the expression of the paternal copies of the genes. [26] [27] However, in PWS there is a mutation/deletion of the paternal copies of the PW genes, resulting in the fetus lacking functioning PW genes. The PW genes are SNRPN and NDN necdin genes, along with groups of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109, 29 copies of SNORD116(HBII-85) and 48 copies of SNORD115 (HBII-52). These genes are located on chromosome 15, located in the region 15q11-13. [28][29][30][31] This so-called PWS/AS region on paternal chromosome 15 can be lost by one of several genetic mechanisms, which in most cases occurs through random mutation. Other, less common mechanisms include uniparental disomy, sporadic mutations, chromosomal translocations, and gene deletions.

The 15q11-13 region is involved in both PWS and Angelman syndrome (AS). While PWS results from the loss of PW genes in this region on the paternal chromosome, loss of another gene (UBE3A) in the same region on the maternal chromosome causes AS. [32] PWS and AS represent the first reported cases of imprinting disorders in humans.

The risk of PWS for a sibling of the affected child depends on the genetic mechanism causing the disease. The risk to siblings is <1% if the affected child has a gene deletion or uniparental disomy, up to 50% if the affected child has an imprinting control region mutation, and up to 25% if a parental chromosomal translocation is present. Prenatal testing is possible for any of the known genetic mechanisms.

Microdeletion in one family of snoRNA HBII-52 eliminated it from playing an important role in the development of this disease. [33]

Studies in human and mouse model systems have shown that the main cause of PWS is the deletion of 29 copies of the C/D box snoRNA SNORD116 (HBII-85). [34] [35] [36] [37] [38]

How is Robert and Christina’s relationship with your other children?

Marina A.: The eldest son, Leon, was waiting for his brother. Kissed my belly when I was pregnant. He has treated him with such tenderness since birth. During feedings, when I poured milk into Robert through the tube, Leon sat next to him and held his brother’s hand, and approached this process very responsibly. But their age difference is less than two years. And now he is so happy about his brother’s success. For example, when Rob is trying to stand, Leon comes running and tells me: “Can you imagine, Robert was standing! I counted to three, and he stood there!” I am very glad that Robert has an older brother, he is a huge support for everyone.

Leon with his younger brother Robert

Marina V.: Christina is my fifth child, and other children see that she is different and ask questions. I believe that the main thing in relationships with children is honesty, so I explain everything to them. They help me look after her, play with her, and do educational exercises together. They worry about her when she needs injections. We call them power shots. The whole family is involved.

The fund has only recently existed, has anyone already applied for help?

Marina V.: Yes, the first contract has already been signed to pay for an important study for children with this diagnosis - polysomnography. We did this for one beautiful little girl from St. Petersburg. This is an expensive study, it is unlikely that it will ever be included in the compulsory medical insurance system, but if such data on the child’s condition is not obtained, it can really lead to death. Today we are ready to pay for several more such studies, but for now our activities are mainly informational.

Diagnosis[edit]

It is traditionally characterized by hypotonia, short stature, hyperphagia, obesity, behavioral problems (particularly obsessive-compulsive disorder-like behavior), small hands and feet, hypogonadism, and mild mental retardation. [39] However, with early diagnosis and early treatment (eg, growth hormone therapy), the prognosis for people with PWS begins to change. Like autism, PWS is a spectrum disorder whose symptoms can range from mild to severe and can change throughout a person's life. Various organ systems are affected.

Traditionally, PWS was diagnosed based on clinical manifestations. Currently, the syndrome is diagnosed using genetic testing; Testing is recommended for newborns with severe hypotension. Early diagnosis of PWS allows timely intervention and administration of growth hormone. Children with PWS are advised to receive daily injections of recombinant growth hormone (GH). GH supports linear growth and muscle mass gain, and may also reduce food preoccupation and weight gain.

The mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternal PWS/AS region on chromosome 15q11-q13. Such testing detects more than 97% of cases. Methylation-specific testing is important to confirm the diagnosis of PWS in all people, but especially in those who are too young to show signs sufficient to make a clinical diagnosis or in those people who have atypical findings.

PWS is often misdiagnosed as other syndromes due to the lack of familiarity with it among many in the medical community. [21] It is sometimes mistaken for Down syndrome simply because of the relative frequency of Down syndrome compared to Down syndrome. [21]

What would you say to families experiencing the syndrome?

Marina V.: When parents first learn about the diagnosis, they try to predict the future: what will happen to us, will we get better or will our condition worsen? I really want people not to waste time, accept the situation and spend time with their children. Children grow up quickly, the love that is here and now should occupy one hundred percent of our time and one hundred percent of our attention.

Marina A.: There is a phrase: “What you can perceive calmly no longer controls you.” I think it applies to our situation: it is important to take time for your feelings, but not to let them control you.

I advise you to study the information, analyze it and understand that this is not a problem, not a terrible problem, but circumstances. They have developed this way, and we cannot influence this fact in any way. But we can love children deeply, we can make every effort to ensure that they have a full life. I believe that a child’s progress, despite the initial data, depends 50% on the parents’ attitude.

Help the fund

Is it easy for such children to socialize?

Marina A.: These children have complex delays in psychomotor and speech development; at an older age they are diagnosed with “mental retardation” (most often of moderate or mild degree), many with disabilities. There is also delayed puberty: fifteen-year-olds look eight years old. Therefore, there is a delay in social development. And here it’s either home schooling or correctional kindergartens and schools. Much depends on the environment and family. Everything is individual: there are cases when children are thin, and in development they are almost as good as ordinary children.

Society and culture[edit]

1680 Painting of Juan Carreño de Miranda from Eugenia Martínez Vallejo, a girl allegedly having PWS [45]

Despite its rarity, PWS is often mentioned in popular culture, partly due to curiosity surrounding the insatiable appetite and fascination with the signature obesity that is a symptom of the syndrome.

The syndrome has been shown and documented on television several times. Fictional person with PWS featured in the episode "Dog Eat Dog" of the television series CSI: Crime Scene Investigation

, which aired in the United States on November 24, 2005.
[46] In July 2007, Channel 4 aired a 2006 documentary entitled Can't Stop Eating
, surrounding the daily lives of two people with PWS, Joe and Tamara.
[47] In the 2010 episode
Extreme

Makeover : Home Edition, Sheryl Crow helped Ty Pennington rebuild a home for a family whose youngest son, Ethan Starkweather, suffered from the syndrome.
[48] In a 2012 episode of Mystery Diagnosis
on the Discovery Health Channel, Conor Heibach, who suffers from Prader-Willi syndrome, shared his diagnosis. [49]

How do your husbands support you?

Marina A.: I couldn’t have done it without my husband and his support. When I found out about the diagnosis, I called him and cried, and he said: “I don’t understand why you react this way, nothing bad happened, we’ll handle everything.” At that moment he gave me incredible strength. My husband is my biggest support. And we have a very large and loving family, it gives an unshakable feeling of care and protection, endless love and tenderness. Robert definitely feels this.

Marina V.: My husband helps me both psychologically and physically. Always ready to pick up. He is very active with children, and they are not afraid of anything in this life. He does not treat Christina like some unhealthy child - he plays, tickles, and throws her in the same way. But we understand that there are families who do not have this, and men leave. We want to show positive experience that you can still live like this.

Treatment[edit]

PWS has no cure; Several treatments are available to reduce symptoms of the disease. During infancy, subjects must undergo treatment to improve muscle strength. Speech therapy and occupational therapy are also indicated. During their school years, children benefit from a well-structured learning environment and extra help. The biggest problem associated with the syndrome is severe obesity. Access to food must be strictly controlled and restricted, usually by installing locks on all food storage areas, including refrigerators. [20] Physical activity for people with PWS of any age is essential to increase strength and promote a healthy lifestyle. [13]

Daily injections of recombinant GH are indicated for children with PWS. GH supports linear growth and muscle mass gain, and may also reduce food preoccupation and weight gain. [40] [41] [42]

Due to severe obesity, obstructive sleep apnea is a common complication, and positive airway pressure placement is often required. A person who has been diagnosed with PWS may have to undergo surgery. One surgery that has failed to treat obesity is gastric bypass. [43]

Behavioral and mental health problems must be identified early for best results. These problems are best addressed through parental education and training. Sometimes medications are also administered. Serotonin agonists have been shown to be most effective in reducing anger attacks and improving compulsivity. [13]