Introduction

Prader-Willi syndrome (PWS) was first described by Prader, Labhart, and Willi in 1956 as a complex neurodevelopmental disorder that occurs in around 1 in 15,000 to 30,000 of births. It is considered as a rare genetic condition where paternally expressed imprinted genes on chromosome 15; q11.2– q13 are absent.¹

PWS affects how the human body functions as multiple systems are involved. Associations with certain clinical features include growth hormone deficiency, hypotonia, hypogonadotropic hypogonadism, sleep disturbances, reduced pain sensitivity, decreased gastrointestinal motility, and scoliosis . A clinical feature which is well-defined in PWS is the significant change in eating behaviour over time. On the other hand, PWS in infants may exhibit a poor diet and fail to thrive; a continuing and unregulated desire to eat (hyperphagia) develops during childhood. If access to food is not strictly controlled individuals may portray an overwhelming drive to eat. Alongside decreased energy output in individuals with PWS leads to morbid obesity.² 

Characteristics of Prader-Willi Syndrome

Typical features that individuals with PWS possess are being short in height and obese with small hands and feet. As well as dysmorphic facial features including a narrow bifrontal diameter (above the eyes), almond-shaped eyes and fuller cheeks. There is also an impairment in growth hormone regulation in PWS due to the growth hormone deficiency (GHD) in abnormal hypothalamic functioning. 

In children, there is no enhancement in growth due to obesity and during adolescence due to inefficient testosterone and oestrogen levels growth rate declines. This leads to an absence of pubertal growth spurt. Those that suffer from severe GHD from other etiologies suffer from a negative quality of life and possibly psychological symptoms such as poor memory, social withdrawal, and depression.¹

There are certain behavioural phenotypes (traits) and behavioural disturbances in PWS such as a heightened interest in food, skin picking, temper tantrums, managing a change in routine and obsessive compulsive behaviours as well as mood fluctuations. Elevated compulsions in older children and adults with PWS can be measured by Yale-Brown Obsessive Compulsive Scale. 

Children aged between 2 and 7 with the condition engage in more compulsive behaviours in comparison to other children with developmental delay. These behaviours are known to be in relation to the severity of hyperphagia. The behaviours found in PWS that are obsessive and compulsive tend to be ritualistic behaviours of which include arranging objects, ordering, and hoarding.

In PWS the development of speech and language skills are often delayed and problematic, however, the severity does vary between individuals. Some individuals with PWS may be non-verbal while others may develop normal speech and language skills by adulthood. In a typical developing child understanding words begins from birth with expressive language following after three months. At 12 months, most infants can say two words such as ‘mama’ and ‘dada’, however, infants with PWS do not display verbal vocabulary until 18 months and up to six years of age. 

Some of the common features in the condition are reduced oral motor skills, poor speech and sound development and language deficits. The language problems that are seen in PWS are narrative abilities and pragmatics and also deficits in grammar. Poor speech and sound development could possibly be a result of abnormal saliva (thick saliva), cognitive deficits, and hypotonia. 

Reduced oral motor skills as a result of hypotonia also contribute to speech and sound development as the quality of voice, rate of speech and the ability to formulate words are affected. Receptive and expressive language is also poorly developed, such as narrative skills; this affects communication with others in a social and work environment.⁴ 

The explanation for developing poor language skills may be the result of various factors such as a deficit in auditory short-term memory auditory processing skills and temporal sequencing skills. Also in PWS individuals may have difficulty in maintaining a topic, the ability to portray appropriate empathetic speech as well as turn-taking in a conversation.¹

There are numerous health issues that develop due to PWS, these include hyperphagia, obesity, sleep disorders, and diabetes. Accelerated weight gain is commonly seen in individuals with PWS, if food access is not restricted individuals may consume foods around three times more than individuals of their age and body mass index. This is mainly due to having a stronger preference to high caloric diet such as high fat and carbohydrate foods. As well as having a sweeter tooth for sugary foods in comparison to plain, salty or sour foods. 

Additionally, when food is unavailable, inedible food such as pet food may be consumed. Which is due to abnormalities in satiety response (the feeling of being satisfied after eating food) and earlier returns of hunger after meals. If overeating remains uncontrolled this may lead to life threatening obesity and increasing the prevalence to various conditions such as type 2 diabetes, respiratory problems and cardiovascular disease. 

Neuroimaging data of those with PWS has suggested impairment of normal satiety response as a result of hypothalamic dysfunction; and an increase neural activation in the regions of the brain that are associated with appetite, food motivation, and reward. This is due to the constant overeating and the persistent elevated interest in high-calorie-based foods. Research has suggested individuals with PWS require 24 hour supervision due to not having the mental ability to make decisions on healthy eating.¹

Specific independence skills

Independence in individuals with PWS is fairly limited and they require constant supervision. Due to the hallmarks of PWS, such as hyperphagia, temper outbursts, obsessive and rigid behaviours and anxiety.² Personal hygiene is often poorly maintained in those with PWS, particularly oral health. A dry mouth, grinding of teeth and poor overall oral hygiene is often seen in children and adults. 

They are also at a greater risk of experiencing constipation as drinking water is often disliked by those with PWS, likewise it is important to encourage a high fibre based diet alongside water and fluids. Individuals may not wear weather appropriate clothing at times due to having temperature regulation sensitivity. 

They are also sensitive to high and low external temperatures and may not show symptoms of a fever when an infection is present. Another characteristic of PWS is an altered pain response and individuals are not able to feel pain as usual. This can make it challenging to know of a serious injury and a healthcare professional may need to take intervention.³

Although regardless of the genetic subtypes in PWS weakness in socialisation is significant in the condition, it is a relative strength in the daily living skills occupied by those with PWS. This is due to a heightened interest in activities relating to food and food preparation. Research has also found other daily routines are found these include washing and cleaning compulsions.¹

Due to a varied spectrum of PWS some individuals may exhibit high intellectual abilities. For example, a case study of which has been discussed by Schwartz et al of a 23 year old male (P) graduated with a diploma and would like to attain long term employment. However, due to the P’s rigid behaviour patterns he was unable to keep employment. P wanted tasks to be completed in a certain way as well as arguing with colleagues and managers when he felt they were ‘wrong’.²

The hallmarks of PWS including maladaptive behaviour, cognitive impairment and speech language development in childhood may have an effect on the long term functioning of an individual. Hence it is crucial to understand the cognitive strengths and difficulties that underlies the maladaptive behaviour. This will potentially allow better management and reduce significant stressors for family and caregivers. It has been noted emotional and behavioural characteristics in children and developmental disabilities in adults. 

Therefore it is a priority to manage and treat the most striking symptoms of PWS such as hyperphagia to manage weight but also have an awareness of behavioural; and cognitive implications that are due to behavioural therapy as well as medical treatments including growth hormone and psychotic medications.¹

Managing behaviour in PWS is age-dependent due to the range of problems caregivers and healthcare professionals must utilise a problem based approach to cater each individual accordingly as the severity of symptoms vary across the spectrum of PWS. 

There is no cure for PWS, however early diagnosis and handling the condition with a proactive approach, individuals can lead a full and meaningful lifestyle. And early assessment is needed as well as intervention by a speech-language pathologist to allow the development of future communication skills. For example, in infancy, an early intervention that focuses on improving oral motor skills can potentially improve feeding. Continued assessments are required of speech/sounds and receptive/expressive language skills that will affect voice and creating throughout an individual’s development through life. 

Therapeutic methods could be utilised to improve articulation and language skills. This includes exercises of the mouth, tongue, and throat to improve muscle control as well as techniques to increase vocabulary skills, sentence formation, and improve pronunciation. Other forms of communication could be used such as sign language and communication boards in most severe cases where speech skills are poor. This is important because the inability to communicate may cause greater frustration and problematic behaviours.¹

Future directions and research

In 1993 a diagnosis criteria of listing symptoms and a scoring system was created for PWS. This is still useful today in terms of informing and detecting the syndrome. However, now cytogenetic and molecular techniques are used to diagnose. An example of a cytogenetic technique is Fluorescent in situ hybridization (FISH) is utilised to identify specific DNA sequences on chromosomes. This technique detects mostly all individuals with deletions in the chromosome 15 (q11–q13 region). 

DNA methylation analysis detects methylation pattern and has a sensitivity of around 100%. Currently, practitioners have recommended newborns with persistent hypotonia to first undergo methylation analysis to test for the condition. If methylation analysis is shown positive, this should be followed up with a FISH test to determine whether PWS is a cause of paternal deletion or m-UPD.¹

Summary

The symptoms in PWS all have crucial implications on childhood and long-term functioning of an individual. It is a priority to understand the cognitive strengths and difficulties that underlie the maladaptive behaviour; allowing for better management of PWS. One of the most striking stressors for family, caregivers, and healthcare professionals is the emotional and behavioural problems shown by children and developmental disabilities in adults. Behavioural issues often have a major impact on family and individuals with PWS more than any other aspect of the condition. 

Therefore, it is important to not only manage and treat the most striking features of PWS such as hyperphagia and weight-related issues first, but to also be aware of the secondary behavioural, cognitive implications of behavioural therapy as well as medical treatments including growth hormone and psychotropic medications. Food-related incidents may underlie other behaviours and emotional disturbances, hence it is essential those with PWS work alongside with a dietitian.

Independence in individuals is limited with PWS despite the strengths that have been mentioned. Managing food-related issues are fundamental and do require 24 hour environmental control including keeping food under a lock and key, a disciplined supervision of food access with a low-calorie well well-balanced diet and regular exercise.

Further research is required to completely explore and understand PWS as currently studies have been small, controlled and randomised. Future research should explore the differential treatment effects of individuals with PWS that are based on subtyping and the efficacy of combining psychotherapy and pharmacology to improve outcome in individuals with PWS.