Prader-Willi Syndrome

Introduction

A rare genetic condition known as Prader-Willi Syndrome (PWS) manifests from birth. It typically causes poor muscle tone (hypotonia) in infancy, followed by a constant feeling of hunger (hyperphagia) that begins in early childhood and persists throughout life. This can lead to chronic overeating and obesity if not carefully managed.

People with PWS may also experience behavioral challenges and hormone-related issues. Early diagnosis and management through a multidisciplinary approach can significantly improve the quality of life for individuals with the condition.

Growth, behavior, and learning are all impacted, and ongoing care is necessary to prevent possibly fatal complications.

Here are some essential facts regarding PWS, including its causes and potential remedies.

Your child’s behavior and physical condition may also be affected. Your child has an intense appetite and struggles to feel satisfied after meals due to this problem. Supportive therapy and food management help treat PWS and avoid issues that could harm your child’s health. One of Prader-Willi syndrome’s main symptoms is feeling hungry all the time.

Those who suffer from Prader-Willi syndrome are constantly hungry because they never feel satisfied. We call this hyperphagia. They so typically struggle to control their weight. Obesity is a contributing factor in many Prader-Willi syndrome consequences.

The most effective way to treat Prader-Willi syndrome symptoms is with a multidisciplinary team of experts. The collaborative approach to this complicated ailment enhances quality of life and reduces the likelihood of complications.

Prader-Willi syndrome: What is it?

PWS is a hereditary syndrome that manifests randomly or may be carried in certain individuals. It develops when a section of chromosome 15 is removed or changed. Scientists have discovered that PWS is a complex, multisystem illness because it impacts multiple body systems.

No matter what they eat, patients may not feel full, which is a prominent symptom of the disease. Overeating, morbid obesity, and potentially fatal consequences like diabetes, heart disease, and sleep apnea can result from this condition.

Early infancy is characterized by inadequate feeding and extreme muscle tone, but between the ages of two and six, they develop an intense appetite. If excessive eating is not managed, severe obesity may ensue.

Additionally, PWS usually delays puberty and other developmental milestones in children. Although they are uncommon, life-threatening side effects might happen and include diabetes, sleep apnea, cardiovascular issues linked to obesity, and respiratory disorders.

Prader-Willi syndrome affects whom?

Prader-Willi syndrome is a genetic disorder that occurs randomly during the formation of reproductive cells, meaning that anyone can get it. If the ailment is rare and runs in your biological family, you might carry it.

How frequently does Prader-Willi syndrome occur?

Research indicates that 1 in 10,000 to 30,000 people worldwide suffer from PWS.

Prader-Willi syndrome genetics

The first human condition linked to genetic forming was Prader-Willi syndrome. It arises when the genes acquired from the paternal chromosome’s 15q11–q13 region are not expressed for the following reasons:

• Approximately 60% of paternal 15q11-q13 deletions
• either the mother’s 15s or both of her 15s (about 35%).
• On the other hand, either maternal elimination or paternal uniparental disomy causes Angelman’s syndrome.

Prader-Willi syndrome epidemiology

While all ethnic groups are represented, PWS is said to be significantly more common among white people.

Symptoms

The symptoms of Prader-Willi syndrome can vary greatly and progressively change as a person grows older.

Infants

Among the symptoms that could exist from birth are:

Poor muscle tone. One of the primary indicators in infancy is hypotonia or low muscular tone. Babies may lie with their legs and elbows bent rather than straight. When hugged, they could also feel floppy or like rag dolls.

Distinct facial features. Babies may have almond-shaped eyes, a narrowed skull at the temples, a turned-down mouth, and a thin upper lip when they are born.

Poor sucking reflex. Because their muscles are less toned, infants may have a poor sucking reflex. Poor sucking makes it more difficult for them to feed and reduces the likelihood that they will gain weight at the expected rate.

Generally poor responsiveness. A baby may appear extremely exhausted, react badly to stimulation, struggle to wake up or cry weakly.

Underdeveloped genitals. Men may have a small penis and scrotum. The testicles may or may not be small when they descend from the abdomen into the scrotum. Cryptorchidism is the term for this. The clitoris and labia may be tiny in females.

Early infancy through adulthood

The following are additional Prader-Willi syndrome symptoms that start to show in very early childhood and last throughout life:

Weight growth and food cravings. Prader-Willi syndrome is characterized by a constant need to eat throughout early life. Constant hunger causes people to eat frequently and in huge quantities. This causes rapid weight gain. Eating frozen food or trash, or storing food, are examples of unusual food-seeking habits.

underdeveloped sex organs. A disorder known as hypogonadism happens when the ovaries in women and the testes in men produce little to no sex hormones. This results in delayed or incomplete puberty and sex organ development. The majority of people with Prader-Willi syndrome are unable to conceive. Women may never get a period or may not have one until their 30s if treatment is not received. Men’s voices might never get completely deep, and they might not have much facial hair.

Poor physical development and growth. Insufficient production of growth hormone can result in inadequate muscle mass, high body fat, and a reduction in adult height. Hypothyroidism, or insufficient thyroid hormone production, is one of the several endocrine issues that may arise. A further endocrine issue is central adrenal insufficiency, which prevents the body from reacting appropriately to infections or stress. Insufficient production of growth hormone can result in inadequate muscle mass, high body fat, and a reduction in adult height. Hypothyroidism, or insufficient thyroid hormone production, is one of the several endocrine issues that may arise. A further endocrine issue is central adrenal insufficiency, which prevents the body from reacting appropriately to infections or stress.

Having trouble learning, thinking, and solving difficulties. Cognitive impairment is the term for this. People with learning impairments can be adults or children without cognitive disability. Cognitive impairment is the term for this. People with learning impairments can be adults or children without cognitive disability.

Delayed motor skills. Walking and sitting up are two physical milestones that toddlers with Prader-Willi syndrome frequently achieve later than typical kids.

Speech problems. Speech delays are common. The inability to talk clearly and choose words may persist into adulthood.

Behavioral problems. When they aren’t given nourishment, they could have tantrums. They might object to routine modifications. Other mental health issues could arise, like skin removal and anxiety.

Sleep conditions. Prader-Willi syndrome can cause sleep disorders in both adults and children, including irregularities in the normal sleep cycle. They might also have sleep apnea, a condition that stops breathing while you’re asleep. In addition to making kids extremely drowsy during the day, these factors may worsen behavioral issues.

Other symptoms. They may also have dental issues, close vision, hip issues, decreased salivary flow, and other visual issues. Additional symptoms include hypopigmentation, or a loss of pigment, which results in pale skin, eyes, and hair. It’s possible that they can tolerate more discomfort than the typical individual.

When to see a doctor

Early detection of problems, such as stunted growth and development, which may be a sign of Prader-Willi syndrome or other disorders, can be facilitated by routine well-baby exams. If you have any worries about your child’s health in between well-baby checkups, schedule a visit with their doctor.

Causes

The cause of Prader-Willi syndrome is unknown, but it is thought to be related to genes in a section of chromosome 15.

Every gene is found in pairs, except those linked to sex traits. On the other hand, some gene types usually function alone.

A gene on chromosome 15 that is either missing or changed disrupts the hypothalamus’s ability to function normally. Ineffective hypothalamic function can impact appetite, growth, sexual development, body temperature, mood, and sleep.

Identifying the gene mutation that produced Prader-Willi syndrome can aid in genetic counseling.

Risk factors

One of the genes, for instance, may be absent. This error may be inherited. Determining the likelihood of having another kid with Prader-Willi syndrome might be aided by a genetic counselor.

Complications

Obesity-related complications

In addition to having poor muscular mass, persons with Prader-Willi disease are constantly hungry. They may therefore consume fewer calories and engage in less physical activity. They are susceptible to obesity and the associated medical issues because of several variables, including:

• Type 2 diabetes.
• High blood pressure.
• High cholesterol.
• Heart disease.
• Sleep apnea.
• Additional issues include a higher risk of gallstones and liver damage.

Complications of not making enough hormones

Inadequate hormone production can lead to the following complications:

Sterility. The majority of women with Prader-Willi syndrome are unable to conceive, though some have been known to do so.
Osteoporosis. Osteoporosis makes bones weaker. Both hormones promote healthy bones.

Other complications

Additional issues caused by Prader-Willi syndrome include:

Choking and stomach rupture. The stomach might swell more than usual with binge eating, which is the practice of consuming huge quantities of food quickly. Choking is another risk of binge eating. Rarely, overeating can cause people’s stomachs to explode.

Dental problems. When these issues are coupled with inadequate oral care, gum disease, and cavities may result.

Reduced quality of life. Participating in social activities, receiving a quality education, and family functioning can all be impacted by behavioral issues. These problems lower the quality.

Diagnostic criteria

With the availability of diagnostic tests, they should assist in raising suspicions and guarantee that all suitable individuals are examined without suffering the costs and concerns associated with needless testing.

• Five points, comprising four main criteria, are needed from birth to age three.
• Eight total points, comprising five primary requirements, are needed from age three to adulthood.

Major criteria (1 point each):

• Central hypotonia in newborns or infants with a weak suck. With age, this gradually becomes better.
• Feeding issues during infancy or failure to flourish.
• Excessive weight increase in children aged one to six. Significant variations in obesity have been seen among patients from various nations. The differences are believed to be explained by variations in management.
• Facial characteristics (almond-shaped eyes, narrow face, etc.).
• Genital hypoplasia and/or delayed or incomplete gonadal development are symptoms of hypogonadism, which is not invariably linked to infertility in males.
• Cryptorchidism is widespread.
• They might not be able to walk or sit until 12 or 24 months.
• Any suitable molecular deviation in this chromosomal region, such as deletion 15q 11-13, is considered a chromosomal abnormality.

Minor criteria (0.5 points each):

• Reduced fetal activity, slowness, or feeble crying in infancy, which becomes better with age.
• Defining behavioral issues (usually obsessive/compulsive behavior or outbursts).
• A sleep disorder or sleep apnea.
• Fair skin and hair, or hypopigmentation.
• Tiny feet and hands.
• Small hands with a uniform ulnar border.
• Irregularities of the eyes (esotropia, myopia).
• Speech articulation issues.
• Picking at the skin.

Other potential Prader-Willi syndrome symptoms, many of which are linked to hypothalamic issues:

• Elevated threshold for pain.
• Less vomiting.
• In one group of 145 patients, 66.7% had either kyphosis or scoliosis at skeletal maturity.
• Despite other sexual development being delayed, early adrenarche (pubic or axillary hair before age 8) occurs.
• Early-onset type 2 diabetes, sometimes referred to as “maturity-onset diabetes of the young” (MODY), has been associated with obesity.
• Hypogonadism-related osteoporosis. This can result in pathological fractures that are difficult to identify right away, in addition to having a high pain threshold.
• They show a unique ability for jigsaw puzzles.
• Different IQ strengths—verbal vs performance IQ—are present in genetic variants of the disorder.
• Compared to people who are just obese, PWS patients walk differently.

How is a diagnosis of Prader-Willi syndrome made?

During the examination, a healthcare professional will check for physical indications of the illness and ask you about your child’s behavior and feeding patterns. Your doctor will perform a genetic test, a blood test that looks for abnormalities caused by alterations in your child’s DNA if they suspect PWS.

Identification of Prader-Willi syndrome

Fluorescence in situ hybridization (FISH) and DNA methylation analysis can distinguish PWS from Angelman’s syndrome in deletion instances and diagnose PWS in all three kinds of PWS.

Endocrinopathies, including growth hormone deficiency, hypogonadism, hypothyroidism, central adrenal insufficiency, and bone health/vitamin D inadequacy, should be monitored and screened for.

HbA1c, lipids, and transaminases should be measured in all patients at puberty and then every year if the patient is obese. All PWS patients receiving GH medication should have their HbA1c levels tested once a year.

Educational and/or psychological assessment is also necessary.

Differential diagnosis

• Obesity.
• Fragile X syndrome.
• Cryptorchidism.
• Short stature.
• Hyperphagic short stature syndrome.

Treating and managing Prader-Willi syndrome

Speech therapy, psychiatric care, intense rehabilitation, and, if the right conditions are met, growth hormone treatment are the methods used to treat Prader-Willi syndrome. Preventing malnutrition in the early stages of childhood and the development of excessive weight in later years requires careful planning and implementation of nutritional management, which is a crucial component of management.

A balanced strategy is necessary:

To deal with behavioral issues that arise throughout childhood, family support is crucial. To prevent future obesity, the child must be kept from consuming excessive amounts of food. Their energy needs are only around 75% of those of a typical child, and hyperphagia can occasionally be harmful due to its tendency to cause large dilatation of the stomach. Regular exercise is really important.

It could be beneficial to get advice from a pediatric gastroenterologist, endocrinologist, psychologist, psychiatrist, dietitian, occupational therapist, speech therapist, exercise adviser, and orthopedic specialist. The outcomes of bariatric surgery have been poor when compared to typical, obese teenagers.

It is crucial to manage the period of transition from childhood to maturity, and placement in a residential home might need to be taken into account. The general practitioner will continue to offer treatment during the transition and as an adult. Among the specific PWS-related factors to take into account during a health examination are:

• Obstructive, central, or mixed sleep apnea—even in cases where weight is not an issue.
• Scoliosis, kyphosis.
• Osteoporosis.
• Oedema.
• Cellulitis.
• Hypothyroidism.
• Gastroparesis.
• Type 2 diabetes.
• Skin infections (a consequence of skin-picking).
• Squint, myopia.

Pharmacological

It was once believed that growth hormone therapy could worsen scoliosis, however, this has now been disproved.

Drugs that restrict appetite don’t work. Although it has little effect on behavior or weight, long-acting octreotide decreases ghrelin secretion.

Although a lot of medications have been employed to change behavior, they are usually ineffective or even harmful. The drug olanzapine might work.

Fluoxetine with haloperidol can be useful at times.

Although they don’t have an antidepressant effect, selective serotonin reuptake inhibitors (SSRIs) appear to have a generic behavior-stabilizing impact, reducing outbursts, irritability, and perseverance.

With caution, you can try any of these medications.

Genetic counselling

• The deletion occurs rarely and has a ≤1% recurrence incidence (unless the father has a rare chromosomal rearrangement).
• Maternal uniparental disomy 15, which usually develops de novo, has a ≤1% recurrence probability unless either parent has a Robertsonian translocation.
• When a microdeletion in the bonding center occurs in some individuals with imprinting defects, it may be familial and has a 50% chance of recurrence.

People with Prader-Willi syndrome may have a higher quality of life if they receive early diagnosis and therapy. Most likely, the ailment will be managed by a group of medical experts.

An endocrinologist, a physician who treats hormone disorders, may be on your child’s team along with a behavior specialist, a dietician, an occupational and physical therapist, and a speech and language therapist.

Even though particular therapies vary based on symptoms, the majority of kids with Prader-Willi syndrome will require:

Good nutrition. Because they have decreased muscular tone, many babies with Prader-Willi syndrome struggle to eat. The development of your child will be monitored by them.

Human growth hormone (HGH) treatment. Prader-Willi syndrome patients benefit from HGH medication as they grow. Additionally, it improves muscle tone and reduces body fat. Adults may also be treated with HGH. You can discuss potential dangers and determine whether your child would benefit from HGH with an endocrinologist, a physician who handles hormone disorders.

Sex hormone treatment. Because of the low levels of sex hormones in your child, your endocrinologist may suggest hormone replacement therapy, which includes testosterone for males and estrogen and progesterone for females. Typically, hormone replacement therapy begins when your child reaches the typical puberty age. Osteoporosis, another name for bone weakening, may be prevented by it.

Weight management. A dietician can assist you in developing a nutritious, low-calorie diet that will help you control your child’s weight while guaranteeing adequate nourishment. To maintain balanced nutrition on a low-calorie diet, extra vitamins or minerals can be needed. Your child’s physical functioning and weight control can be enhanced by increasing physical activity and exercising.

Treatment of sleep disturbances. Daytime drowsiness and behavioral problems can be resolved by treating sleep apnea and other sleep disorders.

Various therapies. Learning social skills, interpersonal abilities, and age-appropriate behaviors through developmental therapy may also be beneficial. These kinds of therapy are typically offered in early intervention programs for infants and toddlers in the United States through the health department of a state. Educational planning and support can help improve learning throughout the school year.

Behavior management. It could be necessary to establish timetables for your child and impose strict limits on their access to and consumption of food. It’s critical to be explicit about your expectations for your child’s behavior. Occasionally, medication is required to treat behavioral issues.

Mental healthcare. Skin picking, anxiety, obsessive-compulsive behaviors, and mood disorders can all be treated by a mental health expert, such as a psychologist or psychiatrist. Mental health symptoms may be alleviated by medication.

Other treatments. Managing particular symptoms or problems may be one of them. Screenings for scoliosis or vision issues, for instance, may reveal abnormalities, as may tests for diabetes or hypothyroidism.

Feeding and weight management

For babies with PWS to acquire weight, unique feeding techniques are frequently required.

The inability of older children and adults with PWS to regulate their hunger is typically caused by their brains’ inability to recognize when they have had enough to eat.

Controlling weight and eating requires weight management.

Obesity-related problems can be lessened with weight control.

Change to adult care

In residential care facilities, many persons with the disease can work, eat well, live comfortably, and engage in recreational activities.

As your child gets closer to adulthood, think about these plans:

• Look for adult resources and services in your area through your child’s school and groups like the Prader-Willi Syndrome Association in the United States.
• To ensure your child is looked after and watched over in the future, research guardianship matters, wills, and special needs trusts.

Lifestyle and home remedies

To assist you in caring for your kid who has Prader-Willi syndrome, consider the following advice:

Learn about Prader-Willi syndrome. Learn about the disease and develop a care plan with your child’s medical team to address any problems or symptoms. Controlling weight and hormone levels can enhance behavior and development while reducing issues.

Stick to a strict meal plan. To assist your child learn expectations and establish routines, plan mealtimes and the kinds of food that are offered at meals. When serving meals, use small servings and avoid purchasing high-calorie snacks. Garbage cans, cabinets, refrigerators, and pantries should all be locked.

Encourage regular daily activity. Your child can improve their physical functioning and manage their weight by exercising and increasing their physical activity.

Set limits. Set clear expectations for behavior and a strict routine. If required, ask your healthcare team for advice on problem-solving strategies.

Schedule regular medical care. Consult your healthcare provider about scheduling routine check-ups and tests to look for issues or consequences.

Coping and support

It can be challenging and time-consuming to raise a child with Prader-Willi syndrome. The entire family may be impacted by managing behavioral, medical, and eating disorders.

Consider doing the following actions for assistance and coping:

Talk to a mental health professional. See a mental health counselor or therapist if you’re struggling to cope or feel overburdened.

Join a support group. It can be beneficial for some people to speak with others who have gone through similar things. Ask your healthcare provider about nearby family support groups.

Getting ready for your visit

Your child may see your family doctor initially. It may be necessary for your child to see a pediatric endocrinologist in addition to other physicians.

The following details can help you get ready for your child’s appointment.

Actions you can take

To get ready for the meeting, make a list of the following:

• What symptoms has your child been experiencing, and how long has it lasted?
• The names and dosages of any medications, vitamins, herbs, or other supplements, as well as your child’s recent illnesses and medical conditions, are all important medical details.
• Questions to pose to the medical practitioner caring for your kid.

The following are some fundamental inquiries to make of your healthcare provider:

• What’s probably the cause of my child’s symptoms?
• What tests is my child required to take?
• Which therapeutic strategy would you suggest?
• What outcomes can one anticipate from treatment?
• What adverse therapeutic effects are possible?
• What kind and frequency of follow-up is required?
• How likely are long-term issues for my child?
• Could you recommend some educational resources and nearby support services?

Your doctor’s expectations

The doctor or other healthcare provider will probably ask you several questions. Be prepared to respond to them so that you can review the issues you wish to emphasize.

Some inquiries concerning your child are:

• What is the frequency and amount of your baby’s meals?
• Does your infant struggle to suck?
• How does your infant wake up?
• Do you think your infant is weak, exhausted, or ill?

Among the queries concerning young children are:

• What is your child’s daily intake?
• Does your child constantly search for food?
• Does your child steal or sneak food, or does he or she eat anything out of the ordinary?
• Does your kid throw fits?
• Are there any other concerning behaviors that your child exhibits?

You can maximize your time with the healthcare provider by being prepared for these inquiries.

What are some ways to avoid Prader-Willi syndrome?

In many instances, the cause is an unplanned, random genetic alteration rather than an action taken by the biological parents before or during pregnancy. Consult your healthcare practitioner about genetic testing to find out more about your chances of having a child with a genetic problem.

What is the prognosis for those who have Prader-Willi syndrome?

It is not just children who apply helpful tactics. A large number of adults with PWS may require specialist care and may be admitted to residential homes for individuals with comparable disorders. It’s possible that some PWS individuals can work in supportive settings.

In maturity, the emphasis of supportive interventions moves to behavioral challenges, such as maintaining muscle mass with growth hormone medication and managing weight to prevent obesity and obesity-related disorders. The death rate for people with PWS has dropped by roughly 1.25% a year as care has improved.

If my child is diagnosed with Prader-Willi syndrome, what can I expect?

A normal lifetime is achievable for many people with Prader-Willi syndrome if they get early and continuous therapy. It’s usual to need extra school aid. To help your child control their eating, your provider may advise you to see a nutritionist to help create a diet and meal plan. One excellent resource for parents and families is to join a support group or schedule an appointment with a mental health expert. It can assist them in adjusting and learning how to support their child’s development and reach their greatest potential.

Can Prader-Willi syndrome be cured?

A cure for Prader-Willi syndrome does not exist. Research on the illness is still being conducted.

Prognosis

According to demographic surveys, the annual death rate in PWS is believed to be 3%.

Living With

When should I consult a medical professional?

If kids miss developmental milestones throughout infancy, it’s extremely critical that they see their provider. Early diagnosis allows the doctor to assist you manage your child’s illness, help them reach developmental goals, and help them control their food to lessen the condition’s effects.

Which queries should I pose to my physician?

• How can I prevent my child from being obese?
• How is my child going to be treated?
• Which behavioral disorders could my child be experiencing?
• Do we have access to support groups to help us understand and manage PWS?
• Should I get genetic testing for other members of my family?

Conclusion

PWS is an uncommon genetic condition that impacts individuals from birth till the end of their lives. Sufficient assistance may reduce symptoms, prevent complications, and enhance an individual’s general quality of life. People with PWS may require continuous help, yet they can live well into adulthood.

FAQs

Reference

• Prader-Willi Syndrome. (2025, March 19). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21016-prader-willi-syndrome
• Prader-Willi syndrome – Symptoms and causes. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997
• Prader-Willi syndrome – Diagnosis and treatment – Mayo Clinic. (n.d.). https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/diagnosis-treatment/drc-20356002
• Prader-Willi syndrome. (2021, December 17). https://patient.info/doctor/prader-willi-syndrome-pro
• Healthdirect Australia. (n.d.). Prader-Willi syndrome. Healthdirect. https://www.healthdirect.gov.au/prader-willi-syndrome
• Marcin, A. (2024, April 12). Understanding Prader-Willi syndrome. Healthline. https://www.healthline.com/health/prader-willi-syndrome