Overview
Prader-Willi Syndrome is a genetic disorder that affects a person physically, cognitively and behaviourally. It is estimated that around 350,000- 400,000 people worldwide have the condition1 and it affects genders and all ethnicities equally.2 The syndrome was first described in Switzerland in 1956.3
One of the main features of Prader-Willi syndrome is over-eating which leads to obesity and has serious effects on health and life expectancy. Other symptoms include low muscle tone and poor feeding as an infant then short stature, certain facial features, delays in intellectual development, and behavioural problems as the person gets older.4
There is currently no cure for Prader-Willi syndrome but symptoms can be managed to enhance health, life expectancy and quality of life.
In this article, we look at the features of Prader-Willi syndrome and focus on the impact of obesity and why it is important to manage this in terms of health and quality of life.
What is Prader-Willi Syndrome?
Prader-Willi syndrome is a complex genetic disorder which occurs in approximately 1/10000- 1/300000 births.5 It was first described in 1956 in Switzerland by Andrea Prader, Alexis Labhart, and Heinrich Willi.3
Symptoms of Prader-Willi Syndrome
The syndrome can have many features to differing extents including:
- Obesity
- Short stature
- Overeating or hyperphagia
- Developmental delay
- Learning disability
- Behavioural problems
- Hypogonadism
- Altered pain threshold
- Inability to vomit
These issues develop over time. Generally, in infancy, the parents or caregivers will seek medical help because the baby is not sucking, has hypotonia, and appears to be failing to thrive.
Obesity is one of the main symptoms associated with the condition and the key cause of poor health and reduced life expectancy. This is mainly the result of over-eating, or hyperphagia, due to insatiable appetite.
Genetic basis and inheritance patterns of Prader-Willis Syndrom
The condition is caused by a genetic mutation at chromosome 15 and diagnosis is made by genetic screening, a full patient history and observation of the specific features of the condition.5
The risk factors for Prader-Willi syndrome are not known and the genetic error is thought to manifest randomly and is not believed to be hereditary.
Clinical features and symptoms of Prader-Willis Syndrome
The clinical features of Prader-Willi syndrome progress from infancy to adult.
Infancy
In a young baby, the initial presenting problems tend to be low muscle tone (hypotonia), poor sucking, and failure to thrive. These problems will usually be the reason a parent seeks medical advice in the first instance.
Childhood into adulthood
As the child with Prader-Willi syndrome gets older, the following issues may develop:
- Short stature
- Recognisable facial features
- Overeating or hyperphagia
- Obesity
- Learning disability
- Behavioural issues
The most serious symptom of the condition is obesity due to over-eating and low physical activity, and this can become life-threatening.
The association between Obesity and Prader-Willi Syndrome
One of the main issues associated with Prader-Willi syndrome is obesity. It is believed that the prevalence of obesity is zero in infancy due to feeding problems, but it increases to around 90% in adulthood6 as appetite increases.
Obesity develops due to hyperphagia, poor appetite control, and reduced mobility due to low muscle tone and learning disability.
Importance of understanding and managing obesity in individuals with Prader-Willi Syndrome
It is important to look at obesity in relation to Prader-Willi syndrome because the main cause of reduced life expectancy in those with the syndrome is obesity.
Why is obesity a problem?
In any population, obesity can lead to
- hypertension
- diabetes
- heart disease
- reduced mobility
- joint problems
- increased risk of some cancers
These are all serious conditions which can seriously affect health, quality of life and life expectancy.
Therefore, in Prader-Willi syndrome, where obesity is a predominant feature, these health problems are prevalent. For example, it is estimated that 25% of adults with Prader-Willi syndrome have type 2 diabetes.6 A study in Japan showed that 19.4% of adults with Prader-Willi syndrome had hypertension and 40% of people had Type 2 diabetes.7
Management of Prader-Willi Syndrome
Management and treatment aim to enhance health and quality of life for people with Prader-Willi Syndrome and their families or caregivers. Quality of life is also adversely affected by Prader-Willi syndrome. In one study, increased weight was identified as significantly impacting family functioning, social activities and relationships.8
Multidisciplinary care team for individuals with Prader-Willi Syndrome
The approach to the management of Prader-Willi Syndrome should be multidisciplinary and ideally could include the input of a GP, paediatrician, geneticist, dietitian, specialist nurse, physiotherapist, occupational therapist, and psychologist working with the child and the family holistically.
Treatment of obesity
After around two years of age, the child with Prader-Willi Syndrome usually begins to gain weight as their appetite increases, often becoming uncontrollable into adolescence.
Managing this change in appetite is vital and can delay the early onset of severe obesity. Calorie intake must be restricted along with the promotion of physical activity to prevent life-threatening obesity.
Currently, the main treatment for over-eating or hyperphagia associated with Prader-Willi syndrome is to control the environment in which there is access to food. This can include strategies such as locked kitchens or kitchen cupboards and continuous supervision.
This can be extremely difficult when the individual has an insatiable appetite but also a learning disability and challenging behaviour. Support from the multidisciplinary team is vital in these instances.
The approaches to dietary control which can be used individually or as part of a tailored treatment plan established with multidisciplinary input will include:
- Calorie restriction
- Nutritionally balanced diets
- Meal structure
- Supervision
- Physical activity and exercise programs
Medication
Growth hormone therapy is the recommended standard treatment for children with Prader-Willi syndrome because it is found to improve body composition of body fat and lean body mass by increasing muscle mass and energy expenditure, linear growth and IQ development.9
Other drugs
There are several studies on anti-obesity medications for use in Prader-Willi syndrome. Unfortunately, there are no definitive conclusions on the effectiveness of their use yet.
Surgical options for extreme cases
Bariatric surgery for extreme obesity – such as gastric bypass, gastric balloon or band – has been shown to have limited efficacy in terms of benefit over risk.10
Future directions and research
Currently, there is no effective treatment for obesity in Prader-Willi syndrome other than dietary restriction and physical exercise along with behavioural modification. There is no drug or surgery which currently helps consistently.
This area requires more input in terms of research and development.
Reduction in obesity will improve the health and quality of life for the person with Prader-Willi syndrome and improve that of their families or caregivers.
Summary
Prader-Willi syndrome is a genetic condition which significantly impacts health and life expectancy due to an insatiable appetite and over-eating, which leads to obesity and further health complications. It can also affect the quality of life for the individual and their caregivers. Currently, the only treatment for obesity is dietary restriction and supervision of intake.
Until there is a specific treatment for overeating and weight gain in Prader-Willi syndrome, weight should be controlled with the help of a well-balanced diet and exercise. Multidisciplinary approaches are crucial to supporting caregivers in facilitating these strategies and to the lifelong follow-up and treatment which will enhance the quality of life of individuals with Prader-Willi syndrome.
As of yet, there are not any truly effective medical or surgical treatments for obesity in Prader-Willi syndrome. Some drugs show promise in early research but further investigation is required to improve the health and quality of life of people with the condition and their families.
References
- Butler MG, Thompson T. Prader-Willi Syndrome: Clinical and Genetic Findings. The Endocrinologist 2000;10:3S-16S. https://doi.org/10.1097/00019616-200010041-00002.
- Bohonowych J, Miller J, McCandless SE, Strong TV. The Global Prader–Willi Syndrome Registry: Development, Launch, and Early Demographics. Genes 2019;10:713. https://doi.org/10.3390/genes10090713.
- Prader A, Labhart A, Willi H. A syndrome characterised by obesity, short stature, cryptorchidism, and oligophrenia following a myotonia-like conditioning infancy. Schweirzerische Medizinische Wochenschrift 1956;86:1260.
- Hurren BJ, Flack NAMS. Prader–Willi Syndrome: A spectrum of anatomical and clinical features. Clinical Anatomy 2016;29:590–605. https://doi.org/10.1002/ca.22686
- Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Invest 2015;38:1249–63. https://doi.org/10.1007/s40618-015-0312-9
- Höybye C, Tauber M. Approach to the Patient With Prader–Willi Syndrome. The Journal of Clinical Endocrinology & Metabolism 2022;107:1698–705. https://doi.org/10.1210/clinem/dgac082.
- Kawai M, Muroya K, Murakami N, Ihara H, Takahashi Y, Horikawa R, et al. A questionnaire-based survey of medical conditions in adults with Prader-Willi syndrome in Japan: implications for transitional care. Endocr J 2023;70:519–28. https://doi.org/10.1507/endocrj.EJ22-0561.
- Erhardt É, Molnár D. Prader–Willi Syndrome: Possibilities of Weight Gain Prevention and Treatment. Nutrients 2022;14:1950. https://doi.org/10.3390/nu14091950.
- Meade C, Martin R, McCrann A, Lyons J, Meehan J, Hoey H, et al. Prader‐Willi Syndrome in children: Quality of life and caregiver burden. Acta Paediatrica 2021;110:1665–70. https://doi.org/10.1111/apa.15738.
- Passone CDGB, Franco RR, Ito SS, Trindade E, Polak M, Damiani D, et al. Growth hormone treatment in Prader-Willi syndrome patients: systematic review and meta-analysis. Bmjpo 2020;4:e000630. http://dx.doi.org/10.1136/bmjpo-2019-000630.
- Scheimann A, Butler M, Gourash L, Cuffari C, Klish W. Critical Analysis of Bariatric Procedures in Prader‐Willi Syndrome. J Pediatr Gastroenterol Nutr 2008;46:80–3. https://doi.org/10.1097/01.mpg.0000304458.30294.31.
