Introduction

Prader-Willi syndrome (PWS) is a rare neurodevelopmental condition that causes physical, mental and behavioural problems. It is defined as a genetic disease and has implications on the metabolic, endocrine (hormonal) and neurological systems. It can also cause behavioural and intellectual problems.¹

PWS occurs in 1 in 15,000-25,000 live births and is caused by a DNA mutation in a specific region on chromosome 15. This mutation may be due to a genetic error (like a deletion), maternal uniparental disomy (when both sets of a chromosome are inherited from the mother, rather than one copy coming from each parent), or imprinting defects.^1,2

Most cases of PWS are diagnosed during childhood via genetic testing, but it is not uncommon for PWS patients to be adults, especially with the increased improvement in medical care and understanding of the medical condition.² However, the early diagnosis of PWS is important to improve patients' quality of life. 

Physical symptoms of PWS

Symptoms of PWS do vary depending on the patient and they can develop slowly over time.³ Due to defects in chromosome 15, there are malfunctions in the hypothalamus, an important gland in the brain that regulates the production and release of various hormones.³ For example, the hypothalamus produces hormones that influence body temperature, hunger levels, mood, sleep, and sex drive.³ The disruption within the hypothalamus can lead to the following symptoms:

• Obesity and insatiable appetite
• Hypotonia (low muscle tone)
• Growth hormone deficiency

Obesity and insatiable appetite

A common feature of adult PWS is obesity, which is often a consequence of the insatiable appetite (hypergia) triggered by the disrupted hypothalamus. PWS patients may also be overly interested in food and may even exhibit food-seeking behaviour, steal food, or hide it from others. This leads to weight gain and can lead to obesity if not managed.¹

Obesity is associated with the following health risks:⁴

• Heart disease, such as high blood pressure and high blood cholesterol, which can cause heart attacks
• Strokes, where a blood vessels in the brain is blocked or bursts - causing the blood flow to be cut off to a part of the brain, causing brain damage and could lead to partial paralysis
• Diabetes is a disease where the blood glucose levels are too high and the body is unresponsive to insulin being produced. This leads to damage to blood vessels and causes damage to organs
• Breathing problems, such as sleep apnea and asthma
• Osteoarthritis is a long-lasting condition where the joints get swollen and stiff, leading to reduced motion in the joints
• Gallbladder disease due to the high cholesterol levels in the blood
• Kidney disease, is when the kidneys become damaged and can no longer filter the blood properly

Hypotonia (low muscle tone)

Hypotonia is a physical symptom where the patient has a decreased muscle mass and strength.¹ In infants, PWS patients will have poor suck reflex and difficulties in feeding, so medical intervention will be needed. Having a history of hypotonia at birth or during infancy and poor sucking and feeding problems are the main clinical features used to diagnose PWS in adults. 

Hypotonia causes a reduction in muscle strength and this can impact the patient's ability to perform physical activities.⁵ It can also have an impact on patients mobility and coordination, affecting tasks such as walking, standing or climbing the stairs - and this can affect the way they live. Low muscle tone can also lead to orthopaedic (bone) issues like joint dislocation, or scoliosis.

Therefore, management strategies are important to address hypotonia in individuals. These are usually included in occupational therapy and physiotherapy.⁵ Early intervention and ongoing therapy is crucial to optimise motor function and independence which is an important element for adult patients. 

Growth hormone deficiency

Growth hormone deficiency is the most common hormonal symptom of PWS. PWS patients are deficient in IGF-1 (insulin growth factor 1), a hormone that plays an important role in tissue and bone growth during childhood. Its main function is to manage and regulate the effects of growth hormones in the body.¹ As such, PWS patients will often not have a growth spurt during puberty and will be shorter than other adults.¹

Growth hormone treatments therapy options are available and it is used to improve the body’s composition, the patients’ quality of life, and their cognitive function. However, these treatments do have some side effects like joint and muscle pain, burning or numbing feelings, blurred vision and severe headaches.² Both physical and emotional therapy will be needed to manage adult PWS patients. 

Behavioural and psychological symptoms

Motor developmental delay is present in the majority of PWS patients, leading them to suffer from behavioural and learning problems. 

Obsessive-compulsive behaviours

Obsessive compulsive disorder (OCD) is a mental health condition where patients display compulsive behaviour and obsessive thoughts. OCD is commonly seen in PWS patients, with many exhibiting repetitive actions such as picking their skin or hand-flapping. These are thought to act as a coping mechanism in emotional or stressful situations. PWS patients may also follow strict ‘rituals’, such as following the same schedule every day or having specific routines before going to sleep or eating meals. 

As mentioned above, PWS patients may experience ‘insatiable appetite’ which, given their predisposition to OCD, can often lead to obsessive behaviour surrounding food.¹ OCD can cause anxiety and present challenges in daily life for both the patient and their families. It can also affect how the patient interacts with others at school or work. Treatments such as therapy or medicines are often prescribed to manage OCD.

Cognitive impairment

All PWS patients will have some cognitive impairments that can range in severity from low normal intelligence with learning disabilities to full-fledged intellectual disability.³ This can mean that patients with PWS have difficulties with memory and focus. Adaptive therapeutic strategies can be used to help with cognitive challenges.³

Medical complications

PWS patients can suffer from the following medical complications as a result of PWS:

• Sleep disturbances
• Endocrine abnormalities
• Psychiatric disorders

Sleep disturbances

Sleep problems are a common medical condition accompanying PWS. Inability to sleep through the night, disruption of a normal sleeping cycle, reduced rapid eye movement and sleep apnea are examples of what PWS patients may face. Sleep disturbances can have an impact on the overall health of the patient and impact their quality of life.

Endocrine abnormalities

Hormonal distribution is a symptom of PWS. Type 2 diabetes is a medical complication characterised by high blood glucose levels and the body’s unresponsiveness to the hormone insulin. Diabetes is a dangerous medical complication that can cause damage to tissues and surrounding organs and will need to be treated to prevent further health decline. 

Psychiatric disorders 

As described earlier, PWS causes patients to have behavioural and learning difficulties and these can include psychiatric disorders such as anxiety, depression, eating disorders and OCD.

Social implications

The social implications of PWS must be considered for adult patients and their families. Social interactions may be difficult due to cognitive impairment and behavioural problems, and they may struggle with forming friendships and understanding social cues. This can lead to PWS patients becoming isolated, and loneliness is a concern that can impact the patients quality of life.

Independent living for PWS patients will need to be considered, as many PWS patients will need support and assistance with daily routine chores such as cleaning, cooking and managing finances. Independent living can be possible with ongoing training and support from professionals and caregivers. 

Summary

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental condition that causes physical, mental and behavioural problems. PWS is usually diagnosed during infancy or early childhood, but with the improvement in medical care and diagnostic tools, PWS is now being diagnosed in adults too.

PWS is a life-long condition that affects both adults and children and all patients will require medical treatment and management throughout their lives. Early diagnosis of adult PWS is important to improve patients' quality of life and allow them to live healthy and independent lives.