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Prader-Willi Syndrome
Key Genetics
  • Paternal Imprinting on chromosome 15q
    • & Maternal uniparental disomy
Select Physical Characteristics
  • Severe obesity
  • Small hands & feet
  • Almond-shaped eyes
Images adapted from:
National Human Genome Research Institute (NHGRI). Accessed May 5, 2018. https://www.genome.gov/.
Cortés M et al., “Caracterización Clínico-Genético-Molecular de 45 Pacientes Chilenos Con Síndrome de Prader Willi.”
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Prader-Willi Syndrome

Genetics
  • Majority of cases: deletion of select genes within the 15q11-q13 region on the PATERNAL-inherited chromosome.
    • The best studied paternally-expressed gene within this region is SNRPN (Small Nuclear Ribonucleoprotein N). 
  • Minority of cases are due to maternal uniparental disomy.
    • In a minority of cases, there isn't a deletion on the paternal chromosome 15 but rather those genes simply aren't ever inherited from the father (both copies of the genes are inherited from the mother, instead). This is referred to as maternal uniparental disomy.
  • See Genomic Imprinting & Uniparental Disomy
Clinical manifestations
Hypotonia and feeding difficulties in infancy, followed by hyperphagia and obesity in childhood.*
  • Obesity in childhood is secondary to:
    • hyperphagia
    • physical inactivity with an associated decreased metabolic rate
    • inability to vomit
  • Weak cry (in infancy)
  • Genital hypoplasia
  • Delayed acquisition of major motor milestones
  • Behavioral problems
    • Food-seeking behaviors that are extreme: binge eating, forging for food in the garbage, eating frozen foods, etc…
    • Skin-picking, Temper tantrums, OCD, stubbornness
  • Mild to moderate cognitive impairment
  • Hypopigmentation
  • Characteristic facial appearance:
    • Almond-shaped eyes (with strabismus) and a narrow forehead
    • Down-turned mouth with thin upper lip
  • Short stature with small hands and feet
Diagnostic Clinical Criteria
  • In summary, major clinical clinical findings that suggest Prader Willi syndrome include:
    • Hypotonia and feeding problems in infancy
    • Excessive weight gain and hyperphagia in childhood
    • Characteristic facial features
    • Developmental delay
    • Mild to moderate intellectual disability
For complete diagnostic criteria, see Holm et al., “Prader-Willi Syndrome.”
Diagnosis
  • Methylation analysis with fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA).
References
Butler, Merlin G., and Travis Thompson. “Prader-Willi Syndrome: Clinical and Genetic Findings.” The Endocrinologist 10, no. 4 Suppl 1 (July 2000): 3S-16S.
Cortés M, Fanny, Alliende R, M. Angélica, Andrés Barrios R, Bianca Curotto L, Lorena Santa María V, Ximena Barraza O, Ledia Troncoso A, Cecilia Mellado S, and Rosa Pardo V. “Caracterización Clínico-Genético-Molecular de 45 Pacientes Chilenos Con Síndrome de Prader Willi.” Revista Médica de Chile 133, no. 1 (January 2005): 33–41. https://doi.org/10.4067/S0034-98872005000100005.
Holm, V. A., S. B. Cassidy, M. G. Butler, J. M. Hanchett, L. R. Greenswag, B. Y. Whitman, and F. Greenberg. “Prader-Willi Syndrome: Consensus Diagnostic Criteria.” Pediatrics 91, no. 2 (February 1993): 398–402.
National Human Genome Research Institute (NHGRI). Accessed May 5, 2018. https://www.genome.gov/.
Reference, Genetics Home. “Prader-Willi Syndrome.” Genetics Home Reference. Accessed May 4, 2018. https://ghr.nlm.nih.gov/condition/prader-willi-syndrome.

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