Musculoskeletal abnormalities are one of the most common symptoms of Prader-Willi Syndrome (PWS). Manifesting from birth, these symptoms have important implications for the health and lifestyle management of individuals with PWS. Therefore, it is not only important to identify the types of musculoskeletal conditions that are frequently observed but also to understand the impacts and treatment options of each.

In this article, we will understand how PWS results in various musculoskeletal issues, along with a general introduction to the PWS disease. The recommended treatment and management of musculoskeletal conditions will also be described.

Introduction to Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a rare genetic disorder that affects about 400,000 people around the world. Diagnosed in 1 out of every 15,000 individuals, PWS is recognised as the leading genetic cause of obesity in children and equally affects the population regardless of gender or ethnicity.¹

Genetic cause

PWS occurs in individuals who lack genetic material in a specific q11-q13 region of chromosome 15. Healthy individuals contain this chromosome region which they inherited from their father. However, PWS patients most commonly have this region deleted. It is important to note that while PWS has a genetic cause, most PWS cases are random and not inherited from either parent. PWS can be diagnosed through a blood test that detects certain genetic signals that differ from those in healthy individuals.

Due to the complexity of chromosome 15, it is still not clear which genes in this region result in PWS symptoms. Despite this, it is known that loss of the chromosome 15q11-q13 region affects the hypothalamus of our brains. The hypothalamus is responsible for producing important hormones that influence an individual’s growth and eating behaviours. This explains many common symptoms of PWS, including the main presentations of delayed developmental growth and uncontrollable appetite.

Symptoms

The symptoms of PWS present all around the body and change over an individual's lifetime. In infancy, the main symptom is hypotonia, which describes very low muscle tone. Due to this, infants with PWS tend to exhibit difficulties feeding and crying, often requiring tube feeding to aid in nutrition. Importantly, their lack of muscle tone delays their development and growth. PWS infants are therefore often described as “floppy” as they are unable to support their weight.

In early childhood, between around 3-8 years of age, PWS individuals start to show an extreme appetite that leads to overeating and rapid weight gain. They do not experience feelings of satiety from eating and therefore severely overeat if not monitored by others.

Alongside the main symptoms of low muscle tone and obesity, individuals with PWS can also have learning or intellectual disabilities. Irregular sleep patterns, speech impairments, infertility, and a high tolerance to pain are also observed in some PWS patients.

Due to their eating habits, behavioural traits such as sudden anger, stubbornness, and compulsive habits can also manifest over time. Physical traits are also shared among some PWS individuals. These include a narrow forehead, small hands and feet, a triangular mouth, as well as very fair skin and hair.

Musculoskeletal issues in PWS

Musculoskeletal issues are common in PWS. They manifest from infancy and impact the health and lifestyle of PWS patients for their whole lifetime. This includes abnormal muscle tone, but also a variety of skeletal anomalies such as scoliosis, hip dysplasia, and osteoporosis.² Together, these greatly impact the motor abilities of individuals with PWS. We will discuss the most common musculoskeletal issues in PWS and the up-to-date treatment guidance for each.

Muscular abnormalities in PWS

As previously mentioned, low muscle tone (hypotonia) is the first presenting symptom in infants with PWS. Paired with muscle weakness in PWS individuals, infants tend to be very inactive and are late to meet developmental milestones such as sitting or crawling.

While muscle tone and strength improve naturally over time in PWS individuals, up to 37% of PWS adults still suffer from decreased muscle mass.³ An abnormal walking gait and low motor performance are also common in people with PWS. This is partly attributed to the lowered levels of growth hormone (GH) compared to healthy individuals. Additionally, structural and functional differences are observed in PWS patients that could further explain the discrepancy in motor development. Structural differences in muscle fibres have been described across different studies.³ Decreased physical activity in PWS patients can also contribute to low muscle mass and strength.⁴ This is greatly linked to the low muscle tone and high body fat percentage in PWS, although cause-and-effect relationships can be difficult to determine.

Skeletal abnormalities in PWS

Abnormalities in the skeletal structure and bone function are also found in PWS. Together, these are referred to as orthopaedic symptoms of the disease. The most common orthopaedic symptoms of PWS include:

Scoliosis

Scoliosis is where the spine is misshapen and has a twisted or curved structure. For individuals with PWS, there is a large 70% risk of developing scoliosis in their lifetime.⁵ In studies comparing the frequency of scoliosis in PWS patients compared to healthy individuals, scoliosis was detected in over 40% of PWS, while only found in 1-3% of the general population.⁶

It is believed that the lack of muscle tone surrounding the spine leads to an increased likelihood of developing scoliosis. It most commonly develops in young children or during the adolescent period of growth.⁵

Hip dysplasia

Hip dysplasia is a condition where the joint between the hip and the upper thighbone is not properly aligned. The ball and socket joint found in the area becomes partially dislocated in individuals with hip dysplasia.

Almost 40% of PWS patients have hip dysplasia and it is normally diagnosed in children at around 2 years of age.⁶ The age of diagnosis is becoming increasingly early as awareness and screening for hip dysplasia in PWS patients have improved. While hip dysplasia is more common in children with PWS, the condition normally improves over time and with increased physical activity. Therefore, its severity and incidence decrease in adults with PWS.⁶

Lower limb malalignment

Lower limb malalignment describes how the bones in your legs become misaligned. Commonly, it is when your upper leg rotates inward while the bones in your lower leg rotate. This is one of the most frequent orthopaedic malformations found in about 3 out of 4 PWS patients.⁷ The misalignment of the bones in the lower limbs not only causes an irregular walking gait, but also knee, hip, and/or ankle pain.

Foot abnormalities

Differences in foot shape are also observed in individuals with PWS. This includes flat feet, high arch and forefoot irregularities.⁷

Osteoporosis

Osteoporosis describes the condition where bones become weaker, more brittle and prone to breakage. This is commonly found in PWS patients.²

Treatment and management

Screening

Screening is essential in detecting these musculoskeletal conditions in PWS patients, especially as obesity in PWS can sometimes mask skeletal abnormalities. As these conditions manifest from birth, early intervention through physical therapy can be greatly beneficial in PWS individuals. Currently, it is recommended that musculoskeletal screening should start when PWS infants begin sitting up independently and be repeated annually until developmental maturity.⁵ Different types of musculoskeletal abnormalities are also correlated with one another and therefore comprehensive screening of PWS individuals with known musculoskeletal issues remains crucial.²

Notably, scoliosis presents less obviously in PWS patients than in other individuals.⁷ Therefore, screening for scoliosis through routine radiography is essential for the detection of scoliosis in PWS. Hip dysplasia in PWS is also important to screen for due to its early onset in PWS infants.⁶ Recently, due to increased screening and awareness, hip dysplasia has been diagnosed more frequently in PWS infants.

Physical therapy

All individuals with PWS should undergo physical therapy from childhood. This not only can strengthen the low muscle tone found in PWS individuals but also do so without promoting the likelihood of developing skeletal abnormalities over the crucial developmental period.

Physical therapy training has been shown to improve body muscle and fat composition of PWS patients. Developing the correct form in performing skills also prevents low physical activity which is associated with poor outcomes in PWS.⁸

Casts and braces

Casting and bracing can correct for skeletal abnormalities, most commonly scoliosis, by correcting posture in children with PWS. Casting is typically used in younger children and is replaced every few months to account for an individual’s growth and skeletal changes. Bracing is used in older children with severe scoliosis to prevent worsening of the condition. In children awaiting surgical treatment for scoliosis, braces help control the extent of scoliosis until surgery.⁵

Growth hormone therapy

The low levels of growth hormone in PWS individuals are associated with low muscle tone, increased fat mass and decreased bone mineral density. Supplementing PWS patients with growth hormone therapy has been shown to improve their body composition and positively affect muscle strength.⁹ However, more research needs to be conducted on GH therapy to better understand its effects on musculoskeletal issues in PWS.

Surgery

Surgery may be recommended for individuals with severe orthopaedic conditions. Braces can be inadequate in treating scoliosis in patients with PWS. In such cases, a healthcare professional may offer surgical treatment to correct scoliosis or hip dysplasia.⁵

Summary

In conclusion, musculoskeletal issues are found in most PWS patients. These symptoms are caused by low muscle tone and skeletal abnormalities in PWS individuals. Individuals with PWS have an increased risk of scoliosis, hip dysplasia, lower limb malalignment, and osteoporosis than people in the general population. Currently, early detection, physical therapy, growth hormone therapy, and surgery are common treatment options to manage these symptoms in the PWS population.