Prader-Willi Syndrome (PWS) is a complex medical condition with lifelong and, if unmanaged, life threatening implications. First described by doctors Prader, Willi and Labhart in 1956, it affects both sexes and people from all over the world. PWS is a birth defect affecting chromosome 15 and is usually due to an accidental and therefore unpreventable occurrence at conception, which could happen in any family. Rarely is it inherited. Its cause is unknown and neither parent is to blame. Its estimated incidence is approximately 1:15000 births, but it is thought that many people are still undiagnosed.

People with PWS have multiple disabilities during their life. Many of these are thought to be due partly to a hypothalamic dysfunction involving the growth hormone and sex hormone systems, which in turn affect growth, body composition, bone mineral density, hypotonia, sleep, hunger, emotional and sexual development. All of which are affected in PWS.

The syndrome is usually characterised by two distinct stages in childhood and a less distinct third stage later with adolescence. In the absence of treatments the following key features may be recognized. It is important to realise that every child is an individual and there is a wide variation in the expression of each of these key features due to genetic and environmental variability.

Early features: birth to toddler

As a baby they tend to be at or below average birth weight and of average length. Growth rate tends to slow following birth, so that many approach or fall below the 10 % subsequently. Genitals appear underdeveloped, which is especially a concern for boys. Infants usually have very low muscle tone (hypotonia) with a poor developed sucking reflex, necessitating gavage (tube) feeding or use of special teats in most cases. Crying may be absent or weak and feeble in the first year. The infant may therefore be unable to express itself in distressing situations. They may sleep a lot and sleep apneas and other respiratory problems may be present. Waking up infants from excessive daytime naps may be necessary for feeding and play. They seem happy most of the time and it is tempting to leave them by themselves. However, it is important to stimulate the child from as young an age as possible so that physical, visual, auditory and social skills may develop.

Motor milestones, such as sitting, crawling and walking are generally delayed and physiotherapy, occupational and speech therapies are advised. The muscle tone may improve somewhat over time. The infant's failure to thrive and the difficulty feeding are the major concerns of parents at this stage. They are also the cutest, loveliest and friendliest toddlers you may know!

Early childhood
Food: At some stage between one and four years or sometimes later an obsession with food and compulsion to eat develops (hyperphagia). In the absence of a consistent and strict dietary management they may rapidly become overweight and obese. The estimated caloric intake for maintaining a healthy weight for a child with PWS is around 50-70% of that of a normal recommended diet - depending on their activity level. Children with PWS are always hungry and can be very convincing. However, any casually given sweets or snacks may compromise the daily quantity of healthy food at meal times. Also restriction of access to food is generally recommended.
Cooperation of all relations, friends and school personnel is therefore of utmost importance.

Development: At this stage coordination and physical development may have improved and many have learned to walk and ride a tricycle. Some learn to run, skip or even ride a bike at some stage during the primary school years. Yet they may fall more frequently and bruise easily. Fractures are not uncommon and may be overlooked initially. People with PWS often have a high pain threshold and may thus fail to attract attention to the severity of the injury or infection. Speech may be slow to develop in some and learning alternative ways of communication are advised to overcome this period. Once speech develops, most love to chat with you.

Behaviour: Changes in behaviour may also become evident over time with tantrums, stubbornness, argumentativeness, non-compliance and perseverance occurring. Obsessive compulsive behaviours are also frequently noted. Time out, redirection or use of humour is frequently helpful while arguing has little effect and may only cause escalation of the conflict. The person with PWS likes a predictable routine and advance warnings of changes is recommended. People with PWS often regret their uncontrollable temper tantrums; they don't seem to be able to help themselves at the time. Later the issue may be discussed.

Intellectual development: People with PWS usually have mild to moderate learning difficulties. The average IQ is around 70, but this may vary from as low as 40 to normal at 100. Adaptive functioning in society is often below the measured IQ level, probably due to the behaviour and food related problems associated with this syndrome. Some form of special educational support is recommended. Presently many children are successfully integrated in the local kindergarten, preschool and occasionally early primary school. Some may continue at high school, but most will attend special classes or units in Australia at some stage. It is important that the child attends the right educational facility and is not in a stressful environment as this may exacerbate the behavioural problems. Most can learn to read and write to some extent and do simple operations in math. Abstract thinking, comprehension and problem solving may remain difficult. Learning may be improved by using visual and kinetic (hands on) rather than auditory methods. Educational computer games at an appropriate level are often enjoyed, thriving on repetition and praise they can be used for additional learning. Children with PWS often like puzzles and crosswords, and may enjoy a variety of card and board games.

Adolescence
Body composition: Short stature, small hands and feet, and special facial features are characteristic of the syndrome. Yet, outsiders rarely note the typical facial features as the child blends in with the family characteristics. The absence of a pubertal growth spurt reduces final height even more and scoliosis, which may develop, may further reduce appearance. In adolescence, dietary management for a healthy weight is even more difficult to maintain than before. Central obesity (obesity more concentrated in the stomach and trunk areas) may result with all its concomitant cardio-vascular and respiratory risks of early mortality. Weight may be managed, but lapses in control have been associated with rapid increases in weight of a kg/day or more at this age. Diabetes may develop with increasing obesity.

Emotional development: Behavioural problems and mood swings may increase as does the psychosocial burden associated with their short stature, limited physical ability and lack of full sexual development. Psychological problems and depressive symptoms may surface. Although people with PWS are generally warm, friendly and loving, especially towards the young, old and pets, social isolation and dependency on their carers may increase.

Sexual development: Gonadal function is low in both males and females. Boys may have cryptorchidism (lack of descend of the testes), for which they can be treated. Puberty may start early with acne, sweat odour, facial, axillary and pubic hair, but further development may be absent or delayed. Breasts and genitals may be underdeveloped, which may cause great concern to those affected. Periods in girls may be absent, irregular or delayed. Sex hormone replacement therapy may be suggested. Infertility was thought to be universal, but recently two women with PWS have had babies. In one of them fertility was accidentally induced by medication for another problem. Sex education is advised. A mother with PWS may not be able to care independently for her infant and the risk of getting a baby with Angelman syndrome is high.

Treatments
To date there is no cure for PWS. There is also no treatment for the hyperphagia. Behavioural and psychological problems are dealt with in a variety of ways and with a wide diversity of medications.

The only well documented treatment is that of growth hormone (GH) therapy in children, which is currently subsidised in the USA and the European Union. Growth hormone treatment may normalise height, hand and feet size when introduced early. It also has benefits in reducing the excessive fat mass, which is even present in children of normal weight, increasing the muscle mass and bone mineral density, and improving physical ability. Recently, improvements in sleep and respiration and a reduction in depressive symptoms are also contributed to the use of GH therapy. Children on the therapy seem to have a greatly improved quality of life. The therapy has to be closely monitored for any side effects and is still being refined to establish the appropriate minimum recommended dose. Its use in infants and adults is currently investigated.

In conclusion
Life expectancy has greatly improved with early diagnosis and intervention from the teens to the forties.
Weight control is essential to prevent the morbid obesity and its associated risks of early mortality. If weight control is achieved life expectancy may improve although early aging may become an issue.
We are hopeful though, that with the recent increase in research in this syndrome, new treatments will be developed and applied to improve the quality of life of people with PWS.

E. Scheermeyer PhD
Coordinator of the Prader-Willi Syndrome Association of Queensland (Australia) Inc. With thanks to the following pediatric specialists on PWS: Dr B. Y. Whitman (USA) and Dr M. O'Callaghan (Australia) for a review of this documentation.