Introduction

Prader-Willi syndrome (PWS) has been identified as the most common genetic cause of childhood morbid obesity with life-threatening outcomes.¹ Early diagnosis is critical and thankfully, due to its distinctive symptoms, this is usually possible within the first few months of life. 

Present from birth, a key symptom of PWS is their weak muscles (hypotonia) which leads to the babies being called “floppy”.² These infants struggle to latch and feed from their mothers, this must be recognised, as a feeding tube may be necessary to ensure their nutritional intake.

Prader-Willi symptoms change and develop as the individual ages. The appropriate routines and interventions must be in place to support the individual with symptoms such as their uncontrollable appetites (hyperphagia).² Without diet restrictions, individuals with PWS have a higher risk of hyperphagia-related complications and higher mortality rates.³

Although PWS does not currently have a life-altering treatment, with early intervention and effective management strategies, the affected persons can live a relatively normal life. 

What is prader-willi syndrome?

Prader-Willi syndrome is a rare genetic imprinting disorder affecting approximately one in every 15,000 births.⁴

Causes of prader-willi syndrome

PWS is caused by abnormalities on chromosome 15 where the normal expression of several genes in a critical region (15q11-q13) is lost.⁵ The genes in this region are normally expressed by only the father’s chromosome and this is because of a phenomenon called imprinting.⁵ Approximately 60% of cases are caused by random mutations in this region of the father’s chromosome and the other 40% are as a result of anomalous inheritance, for example, two copies from the mother, of the chromosome 15 critical region.⁶

Research is still ongoing to understand the role of the genes in this critical region of chromosome 15 and how the loss of them contributes to the Prader-Willi symptoms. Current theories have highlighted the dysfunctional activity of the hypothalamus in individuals with Prader-Willi – the hypothalamus is an important regulatory organ in the brain for hunger, sleeping, emotions and many more crucial behaviours.⁷ Advancements in our understanding of Prader-Willi help the development of routines and strategies to support individuals with their symptoms.

Signs and symptoms in children

The PWS symptoms will change during the life of the affected person. Some of the symptoms will improve, others will worsen. There are several cardinal symptoms of Prader-Willi which are found in the majority of cases whilst other symptoms, for example, psychiatric ones, will vary across individuals.⁸ 

Image generated by Lauren Bailey with canva.com

Symptoms present from infancy (birth - 2 years old)

Floppiness (hypotonia)

The characteristic “floppiness” found in Prader-Willi babies is caused by their weak muscles and this is usually the first warning sign for their guardians.² 

Weak muscles can have a noticeable effect on the babies:

• Difficulty suckling and therefore feeding, leading to underweight babies
• Weak cries
• Limited movements
• Poor reflexes

As the Prader-Willi babies age, especially with feeding interventions, they typically gain weight and their muscles strengthen. Their range of movements may still be limited for some time, with developmental milestones such as walking delayed until they reach 2 years old, but they are achievable.⁸ 

Children with Prader-Willi will also have delayed speech and language development; infants struggle with producing sounds until they reach 6 months.⁹ 

Distinctive features

It has been noticed that individuals with Prader-Willi share some common distinctive physical features including:¹⁰

• Narrow foreheads
• Almond-shaped eyes
• Vision problems: short or long-sightedness  
• Flat nose bridge
• Thin upper lips and downturned mouths 
• Fair hair, skin and eyes
• Short stature
• Abnormally small hands and feet

Under-developed genitals

Children with Prader-Willi experience delayed puberty (hypogonadism) and this is apparent from birth as they typically have underdeveloped genitals and sex organs. Babies assigned male at birth (AMAB) often have unusually small penises and may have undescended testicles, which may require surgical intervention.² The external genitals and ovaries of babies assigned female at birth (AFAB) are also smaller and under-developed. 

The delayed puberty is severe, with AFAB individuals often starting their periods in their 30s which is much later than the average age of menstruation: between 12 and 17 years old.² AMAB individuals also have delayed development; their high-pitched voices may never deepen and there may be difficulties growing facial and body hair.

Due to the delayed development of their sexual organs, adults with Prader-Willi are typically infertile.² They can engage in normal sexual activities, especially if sex hormone replacement therapies are used to supplement any hormone deficits. 

Symptoms present from childhood (2 years old - 8 years old)

By the age of 8, most individuals with Prader-Willi will present with the symptoms described below. These symptoms can be managed with routines and nutritional interventions to ensure affected adults have a relatively normal life. However, this is a neurological condition with a relatively unknown cause and there aren’t any disease-modifying treatments so individuals with PWS will struggle with these symptoms for their entire lives. 

Abnormal appetites (hyperphagia)

A hallmark feature of Prader-Willi syndrome is hyperphagia: an insatiable appetite.²

This symptom is believed to be caused by the dysfunctional hypothalamus which has a critical role in appetite and the ability to feel full after eating.¹¹ Individuals with Prader-Willi have no control over their appetite and, if unrestricted, will eat whenever food is available. 

In children, this symptom results in a high risk of choking and stomach rupture. This is highly dangerous as, combined with their lower metabolism, individuals with PWS can quickly become morbidly obese which increases their risk of developing heart and blood vessel issues and diabetes.

With strict routines and nutritional intervention, individuals with Prader-Willi are less likely to become obese and develop further health conditions. However, due to the lack of hunger regulation in their brains, they exhibit ‘food-seeking’ behaviours which can be dangerous.¹² For example, individuals may hide or steal food when given the opportunity and may eat inappropriate food such as raw, frozen or rancid food. This puts them at a higher risk of food poisoning. Denying and restricting their food intake can cause violent and aggressive outbursts.

Learning difficulties

Children with Prader-Willi syndrome typically have intellectual disabilities; most PWS individuals have an IQ of less than 70 whilst the current average is above 90.¹³ This likely contributes to their delayed developmental milestones, such as walking and talking. However, it should be noted that they can still attend and achieve in a school environment with appropriate support. 

Challenging behaviour

Whilst children with Prader-Willi are loving, kind and funny, their behaviour can also be very challenging at times. These challenging behaviours will vary across individuals and throughout a child’s lifetime. 

A common trigger for this is when parents restrict their eating habits, as their uncontrollable hunger can cause them to lash out in frustration.¹² If their environment is too noisy or busy, they may feel overstimulated which can also lead to challenging behaviours.

Children with Prader-Willi syndrome may have underlying neurodevelopmental diseases, such as autism, which can also affect their behaviour and development.¹¹

Typical challenging behaviours PWS children exhibit are:

• Verbally such as screaming, yelling and crying
• Physically lashing out
• Stubbornness and being argumentative 
• Repetitive questions or an inability to move on from a particular topic
• Skin-picking

It’s recommended to give children with Prader-Willi syndrome a structured environment and routine and to communicate with patience and empathy. It can be beneficial to give your child space and allow them to calm down by themselves, for example by listening to soothing music and taking deep breaths, before attempting to discuss what upset them. To avoid potential temper tantrums caused by their insatiable appetites, it’s recommended that food is kept out of sight of the individual.¹⁰ 

Skin-picking can lead to the serious concern of cellulitis so children should be monitored and access to their skin reduced by wearing full-length trousers and tops.² It can also be beneficial to keep the child’s nails short and blunt to prevent the damage they can cause. 

High tolerance for pain

Individuals with Prader-Willi syndrome are known for having a high tolerance for pain and for vomiting.¹⁰ This is particularly dangerous as, when combined with their uncontrollable drive to eat, they won’t stop eating even if they are choking or vomiting from eating too much. This also means that they can disregard what others would consider severely painful, for example, appendicitis which requires prompt treatment. 

FAQs

Can prader-willi syndrome go undiagnosed?

The physical characteristics of PWS are quite distinctive in babies and physicians can typically make a diagnosis based on their clinical symptoms such as hypotonia. This can be confirmed in 99% of cases with a blood test which can detect the abnormality on chromosome 15. Due to the distinctive and severe symptoms of PWS, it would be highly unlikely for an affected individual to go through life without a diagnosis.

How can I prevent prader-willi syndrome?

As PWS is a genetic condition, sometimes inherited but mostly due to random defects on chromosome 15 during development, it cannot be prevented. If a family has concerns about passing down a PWS-causing mutation to their children, they can speak to a genetic counsellor for advice.

Can people with prader-willi syndrome live a normal life?

With appropriate diet management and strict routines, individuals with PWS can live a relatively normal life including living up to 60 years. However, due to the critical symptom of uncontrollable hunger, they will likely never be fully independent in their own home. 

Summary

Prader-Willi syndrome is a complex and distinctive disorder which, if undiagnosed or managed incorrectly, can severely impact an individual’s quality of life and life expectancy. 

Critical symptoms which need to be managed are:

• Low muscle tone (hypotonia): This affects a baby’s ability to latch and feed from their mothers and they may require a feeding tube. If this isn’t recognised, the baby may suffer from being under-fed
• Uncontrollable appetite (hyperphagia): The brain systems involved in regulating hunger and appetite are disrupted in individuals with PWS. To stop them from over-eating and becoming morbidly obese in their childhood, their food intake must be strictly controlled

Although there aren’t any effective treatment options for Prader-Willi syndrome, with strict routines and dietary interventions, individuals can live relatively normal lives with an average life expectancy of 60.