Guidelines for Medical Professionals

(Reference: Management of Prader-Willi Syndrome Third edition, edited by Merlin G. Butler, Phillip D.K. Lee, Barbara Y. Whitman. Published by Springer 2006

Prader-Willi Syndrome is a recognisable pattern of altered growth and development. While the etiology and pathogenesis remain unclear, it is beginning to yield to the application of molecular-genetic technology. Affected persons face life as potentially overweight, short, sexually immature, developmentally delayed individuals with poor gross motor skills. Usually at least mildly intellectually delayed, stubborn, egocentric and emotionally labile, they rarely develop the ability to cope independently with their insatiable hunger and require environmental restrictions to prevent life-threatening obesity.

Although PWS is not a common disorder, it is no longer considered rare. Estimates of the incidence vary between 1:10,000 and 1:25,000 [the NZ PWS Association knows of approximately 100 persons in NZ]

This unique disorder manifests abnormalities of growth, learning, and physical development that may provide clues to understanding many larger issues such as eating disorders and weight control, the neurophysiology of behaviour, patterns of genetic inheritance and the genetic control of morphogenesis.

Genetic Diagnosis

see also Genetic Diagnosis

Approximately 70% of patients with the clinical presentation of PWS have been shown to have a deletion of the proximal part of the long arm of chromosome 15, described as 15Q11,q13. The remaining 30% have an apparently normal 15th chromosome. Molecular studies have shown that for patients with PWS who have deletions these deletions are from the paternally derived chromosome 15. In individuals with nondeletion, they have been shown to have two maternally derived chromosome 15.

Although the vast majority of cases occur as sporadic events in families, several familial recurrences have been documented around the world. Genetically, these show an imprinting mutation.

Clinical Diagnosis

"Many clinical features in PWS may be subtle or non-specific while other features are more characteristic for the disorder. The primary features of PWS include infantile hypotonia, feeding difficulties, mental deficiency, hypogonadism, behaviour problems, hyperphagia and early childhood onset of obesity, small hands and feet, endocrine disturbances including recently identified growth hormone deficiency and a characteristic facial appearance (small upturned nose, narrow bifrontal diameter, dolichocephaly, down-turned corners of the mouth, sticky saliva, almond-shaped eyes, and strabismus)" (ref p.7 Ch.1)

For a clinical diagnosis, the following is a consensus diagnostic criteria for Prader-Willi Syndrome. Authors: Holm et al. Published 1993, Pediatrics 91, 398.

To score:
Major criteria are weighted at one point each.
Minor criteria are weighted at one-half point.

Children 3 years of age or younger: five points are required for diagnosis, four of which should come from the major group.

Children 3 years of age to adulthood: total score of eight is necessary for the diagnosis. Major criteria must comprise five or more points of the total score.

Major criteria

  1. Neonatal and infantile central hypotonia with poor such, gradually improving with age.
  2. Feeding problems in infancy with need for special feeding techniques and poor weight gain/failure to thrive
  3. Excessive or rapid weight gain on weight-for-length chart (excessive is defined as crossing two centile channels) after 12 months but before 6 years of age; central obesity in the absence of intervention.
  4. Characteristic facial features with dolichocephaly in infancy, narrow face or bifrontal diameter, almond-shaped eyes, small-appearing mouth with thin upper lip, down-turned corners of mouth (3 or more required).
  5. Hypogonadism - with any of the following, depending on age:
    a) Genital hypoplasia (male: scrotal hypoplasia, cryptorchidism, small penis and/or testes for age (<5th percentile); female: absence or severe hypoplasia of labia minora and/or clitoris.
    b) Delayed or incomplete gonadal maturation with delayed pubertal signs in the absence of intervention after 16 years of age (male: small gonads, decreased facial and body hair, lack of voice change; female: amenorrhea/oligomenorrhea after aged 16)
  6. Global developmental delay in a child younger than 6 years of age; mild to moderate mental retardation or learning problems in older children.
  7. Hyperphagia/food foraging/obsession with food.
  8. Deletion 5q11-13 on high resolution (>650 bands) or other cytogenetic/molecular abnormality of the Prader-Willi chromosome region, including maternal disomy.

Minor criteria

  1. Decreased fetal movement or infantile lethargy or weak cry in infancy, improving with age.
  2. Characteristic behaviour problems - temper tantrums, violent outbursts and obsessive/compulsive behaviour; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, and lying (5 or more of these symptoms required)
  3. Sleep disturbance or sleep apnoea
  4. Short stature for genetic background by age 15 (in the absence of growth hormone intervention)
  5. Hypopigmentation - fair skin and hair compared to family.
  6. Small hands (<25th percentile) and/or feet (<10th percentile) for height age
  7. Narrow hands with straight ulnar border
  8. Eye abnormalities (esotropia, myopia)
  9. Thick viscous saliva with crusting at corners of the mouth
  10. Speech articulation defects
  11. Skin picking

Supportive findings (increase the certainty of diagnosis but are not scored)

  1. High pain threshold
  2. Decreased vomiting
  3. Temperature instability in infancy or altered temperature sensitivity in older children and adults
  4. Scoliosis and/or kyphosis
  5. Early adrenarche
  6. Osteoporosis
  7. Unusual skill with jigsaw puzzles
  8. Normal neuromuscular studies.