Diagnosis PWS Stages Treatment
Diagnostic Criteria for Prader-Willi Syndrome

Prader-Willi Syndrome can now be definitively diagnosed by analyzing blood samples of the individual suspected of having PWS. The most common testing methods include FISH (fluorescence in situ hybridization), High Resolution Chromosomal Analysis, and DNA Methylation. Each of these tests has its own limitations, and it is highly recommended to continue genetic testing until the exact type of PWS is determined. Only certain laboratories in the United States are equipped to test for PWS, so it is best to seek out a geneticist who is knowledgeable about PWS, or refer your pediatrician or physician to GeneTests Laboratory Directory sponsored by Children's Health Care System, Seattle, WA at www.genetests.org for a listing of laboratories that are capable of this function (not every laboratory that performs these tests is included in the database).

For more detailed information about the genetics of Prader-Willi Syndrome, visit the PWSA (USA) website http://www.pwsausa.org/syndrome/Genetics_of_PWS.htm
New Criteria to Prompt DNA Testing for PWS
Age at Assessment   Features Sufficient to Prompt DNA Testing
     
Birth to 2 years   1. Hypotonia with poor suck.
     
2 years–6 years   1. Hypotonia with history of poor suck.
2. Global developmental delay.
     
6 years–12 years   1. History of hypotonia with poor suck (hypotonia often persists).
2. Global developmental delay.
3. Excessive eating (hyperphagia; preoccupation with food) with central obesity if uncontrolled.
     
13 years through Adulthood   1. Cognitive disabilities; usually mild mental retardation.
2. Excessive eating (hyperphagia; preoccupation with food) with central obesity if uncontrolled.
3. Hypothalamic hypogonadism and/or typical behavior problems (including temper tantrums, perseverative and compulsive-like behaviors).
 
Sensitivities and the Percentages of Documentation of the Published Criteria % Affected
     
Major criteria    
Neonatal hypotonia   88
Feeding problems in infancy   79
Excessive weight gain   67
Facial features   88
Hypogonadism   51
Developmental delay   99
Hyperphagia   84
Minor criteria    
Decreased fetal activity   62
Behavior problems   87
Sleep disturbance/sleep apnea   76
Short stature   63
Hypopigmentation   73
Small hands and/or feet   88
Narrow hands/straight ulner borders   82
Eye abnormalities
   68
Thick viscous saliva   89
Articulation defects   80
Skin-picking   83

Modified from PEDIATRICS (ISSN 0031 4005) Vol. 108 No. 5, Pages 5, Copyright © 2001 by the AAP

Reference:
Meral Gunay-Aygun, Stuart Schwartz, Shauna Heeger, Mary Ann O'Riordan and Suzanne B. Cassidy Pediatrics 2001;108;92-DOI: 10.1542/peds.108.5.e92

Cassidy SB. Prader-Willi syndrome. J Med Genet. 1997;34:917–923
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Before definitive genetic testing was available, the diagnosis of Prader-Willi Syndrome was based upon meeting certain clinical criteria. The following criteria for a clinical diagnosis of Prader-Willi Syndrome are based on Holm et al. (Pediatrics 91, 398, 1993). Because infants and young children have fewer symptoms than older children and adults with PWS, the scoring system differed by age group.
 
MAJOR CRITERIA
(Count as 1 point each)
1. Neonatal and infantile central hypotonia with poor suck, gradually improving with age
2. Feeding problems in infancy with need for special feeding techniques and poor weight gain/failure to thrive
3. Excessive (crossing two centile channels) or rapid weight gain on weight-for-length chart after 12 months and before age 6; 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 the mouth (three or more of these characteristics required)
5.
Hypogonadism-includes any of the following, depending on age:
a.

Genital hypoplasia (in males: scrotal hypoplasia, undescended testes, small penis and/or testes; in females: absence or severe hypoplasia of labia minora and/or clitoris)

b. Delayed or incomplete gonadal maturation with delayed pubertal signs after age 16 (in males: small gonads, decreased facial and body hair, lack of voice change; in females: no or infrequent menses)
6. Global developmental delay in a child younger than 6 years; mild to moderate mental retardation or learning problems in older children
7. Hyperphagia (excessive appetite)/food foraging/obsession with food
8. Deletion 15q 11-13 (>650 bands, preferably confirmed by fluorescence in situ hybridization) or other appropriate molecular abnormality in this chromosome region, including maternal disomy. [Editors Note: Most recent methods employ DNA methylation as a preferred analytical technique.].
MINOR CRITERIA
(Count as 1/2 point each)
1. Decreased fetal movement or infantile lethargy or weak cry in infancy, improving with age
2. Characteristic behavior problems-temper tantrums, violent outbursts, and obsessive/compulsive behavior; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, and lying (five or more of these symptoms required)
3. Sleep disturbance or sleep apnea
4. Short stature for genetic background by age 15 (in absence of growth hormone intervention)
5. Hypopigmentation-fair skin and hair compared with other family members
6. Small hands (<25th percentile) and/or feet (<10th percentile) for height age
7. Narrow hands with straight ulnar border (outer edge of hand)
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
(The following are not scored but increase the certainty of a diagnosis of PWS)
1. High pain threshold
2. Decreased vomiting
3. Temperature instability in infancy or altered temperature sensitivity in older children and adults
4. Scoliosis or kyphosis (curvature of the spine)
5. Early adrenarche (pubic or axillary hair before age 8)
6. Osteoporosis (demineralization, or thinning, of the bones)
7. Unusual skill with jigsaw puzzles
8. Normal neuromuscular studies

   
Sum of Minor Criteria Points:____

Sum of Major and Minor Criteria Points:____

Requirements for a Clinical Diagnosis of PWS:
From Birth to Age 3 - Five (5) total points are required, of which four (4) must be from the major criteria list.

Age 3 to Adulthood - Eight (8) total points are required, including at least five (5) from the major criteria list.

Reference:
Holm, V.A., Cassidy, S.B., Butler, M.G., Hanchett, J.M., Greenswag, L.R., Whitman, B.Y., & Greenberg, F. (1993). Prader-Willi Syndrome: Concensus diagnostic criteria. Pediatrics, 91, 398-402
 
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