PWS is characterised by hyptonia and feeding problems in infancy, hypogonadism, characteristic facial features, short stature, developmental delay, obesity and an obsession with food and eating.

Joyce Whittington (UK)

(This is a revised version of Ann Aspinall’s article, published in 2002. It was further updated in 2017.)

What is Prader-Willi Syndrome?
PWS is a genetic disorder with pronounced behavioural characteristics.  Except in rare cases, the genetic fault is new, is not inherited, and arises in the first cell formation at conception.  The characteristic symptoms and behaviours of PWS were first identified by Prader, Willi and Labhart in 1956 (Prader et al, 1956).

PWS is characterised by hyptonia and feeding problems in infancy, hypogonadism, characteristic facial features, short stature, developmental delay, obesity and an obsession with food and eating.

Most people with PWS have mild intellectual disabilities (mean IQ 60-65), with approximately 20% having IQ > 70 and about 22% having IQ < 50. Regardless of measured IQ, most children with PWS have multiple severe intellectual disabilities, and their academic performance is poor for their mental abilities (Whittington and Holland, 2004, 2017).

Genetic information

Prevalence:
The estimated prevalence of PWS is 1 in 22,000 to 1 in 25,000 births (Whittington et al, 2001; Smith et al, 2003; Vogels et al, 2003, Diene et al. 2010))

Recurrence Risk:
In the vast majority of cases, the risk of having another child with PWS is very slight indeed.

Genetics:
Current research has shown that PWS results mainly from one of four genetic abnormalities:

  1. A small deletion of Chromosome 15 (most common; 50-70% of cases)
  2. Chromosome 15 maternal disomy (associated with older mothers; 25-50% of cases)
  3. A translocation of chromosomes involving Chromosome 15
  4. An error in the imprinting of Chromosome 15

Research shows that there are important differences between (1 & 3) and (2 & 4), for example in cognitive abilities and susceptibility to psychiatric illnesses (Whittington and Holland, 2004, 2017)

Clinical diagnosis:
Consensus diagnostic criteria for PWS developed in 1993 (Holm et al) have proven to be useful in arousing suspicion but a blood test is necessary for accurate diagnosis.

New-born baby

  • Usually small, weak and floppy with feeble cry
  • Poor or no suck, leading to feeding problems
  • Reflexes which are usually present at birth may not appear until later
  • Physical features may include: narrow face, almond shaped eyes, small mouth, feet and hands, fair skin and hair (in types 1&3), and small genitalia (more apparent in male babies who often have undescended testes)

Early infancy

  • During the first year of life, the degree of floppiness reduces and motor functions begin to improve (although they are likely to remain delayed or weak)
  • Most infants will sit, stand and walk late
  • Muscle tone is likely to cause later problems with speech
  • A wide range of IQ; maternal disomy has higher verbal ability, deletion has higher visuo-spatial ability
  • Most display a degree of stubbornness
  • Generally placid, cheerful and affectionate babies

Late infancy

  • Most are better at concrete, rather than abstract, concepts (e.g. jigsaw puzzles/ wordsearch)
  • Preoccupation with food:  This can be lessened by good management and strict dietary control but if not monitored weight gain is rapid
  • In many ways food becomes central to their lives as they enjoy:
    • Thinking about it
    • Talking about it
    • Looking at it
    • Preparing it
    • And most of all, eating it

Weight gain in infancy

  • Babies are slow to put on weight but usually catch up in the first year (Butler et al, 2010)
  • Between the ages of 2 and 4 their appetite increases dramatically (believed to be due to hypothalamic abnormality resulting in lack of satiety)
  • Many consume everything that is put in front of them (hyperphagia)
  • This is the beginning of a life-long problem

This weight gain is not only due to excessive food intake, but also to the need for fewer calories than the norm to maintain an acceptable weight because of a low metabolism. Thus there is a combination of seemingly insatiable appetite and a reduced biological need for food.

Primary years
Problems which may begin to appear include:

  • Perseveration
  • Temper tantrums
  • Obsessive and compulsive behaviour
  • Stubbornness
  • Rigidity; intolerance of changes in routine
  • Skin picking
  • Many have poor auditory processing

Teenage years

  • Puberty is usually delayed and incomplete in both sexes
  • Infertility (only 3 recorded cases of babies born to PWS mothers)
  • Tendency to be shorter in height (compared to other family members)
  • The risk of scoliosis is increased
  • Social skill deficiencies become even more apparent

Adulthood

  • All problems from childhood remain, especially those relating to food
  • Sleep problems/sleep apnoea especially in those who are overweight
  • Life expectancy has increased in recent years but few individuals live past their forties
  • Diabetes is frequent in those who are obese or have a family history
  • Psychiatric illness may develop; affective disorder in deletion cases and psychosis in maternal disomy cases.

Interventions

  • Professionals should be involved at an early age:
    • Paediatricians, health visitors, portage workers, physiotherapists, psychologists, speech therapists, dentists, opticians and dieticians
  • Educational intervention is also considered to address cognitive, physical and other developmental delays; teachers should be aware of cognitive differences between genetic subtypes
  • Exercise to improve poor muscle tone
  • Children should be taught to recognise a sensible portion size
  • Visual aids and cues to learning should be used because of poor auditory processing
  • Children cannot estimate the passage of time – they should be given concrete explanations (not ‘in an hour’ but ‘when the clock says…’)
  • Children should be given limits as to how long they can go on repeating questions
  • Strategies for coping with change in routine should be taught
  • Assistance in making simple choices
  • Growth hormone therapy should be considered at an early age to help ameliorate small stature, facial appearance, abnormal body composition and poor muscle tone and be continued in adulthood
  • Repeated revision and consolidation is necessary (because of poor short-term memory)
  • Many find it difficult to work in groups but make progress in 1:1 situations
  • Medication to control psychiatric illness

REFERENCES

Butler JV, Whittington JE, Holland AJ, McAllister CJ, Goldstone AP. (2010)  The Transition between the Phenotypes of Prader-Willi Syndrome during Infancy and Early Childhood. Developmental Medicine and Child Neurology. 52:e88-93

Diene G, Mimoun E, Feigerlova E, Caula S, Molinas C, Grandjean H, Tauber M. (2010) Endocrine disorders in children with Prader-Willi syndrome – data from 142 children of the French database. Hormone Research in Paediatrics 74:121-128

Holm .A, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY & Greenberg F. (1993). Prader-Willi syndrome: consensus diagnostic criteria. Paediatrics, 91:398-402

Prader A, Labhart A & Willi H, (1956). Ein Syndrom vom Adipositas, Kleinwuchs Kryptorchismus und Oligophenie nach myatonieartigem Zustand im Neugeborenalter. Schweizerische Medicinische Wochwenschrift, 86:12601

Smith A, Egan J, Ridley G, Haan E, Montgomery P, Williams K, Elliott E. (2003). Birth prevalence of Prader–Willi syndrome in Australia. Archives of Diseases in Childhood 88:263–264.

Vogels A, Van Den Ende J, Keymolen K, Mortier G, Devriendt K, Legius E, (2003) ‘Minimum prevalence, birth incidence and cause of death for Prader–Willi syndrome in Flanders’, European Journal of  Human Genetics, 12:238–240.

Whittington JE, Holland AJ. Prader-Willi Syndrome: Development and Manifestations. Cambridge University Press, Cambridge 2004

Whittington JE , Holland AJ, Webb T, Butler JV, Clarke DJ, Boer H. (2001) Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi Syndrome in one UK Health Region Journal of  Medical Genetics 38:792-798

Whittington J, Holland A (2017) Cognition in people with Prader-Willi syndrome: insights into genetic influences on cognitive and social development. Neuroscience and Biobehavioural Reviews 72:153-167

Websites:

International Prader-Willi Syndrome Organisation www.ipwso.org/

Prader-Willi Syndrome Association (UK): www.pwsa.co.uk/

GeneClinics: www.geneclinics.org

This article was first published on the site in 2002. It was revised and updated in 2011, and further updated in 2017.