Prader–Willi Syndrome

Reference work entry

Prader–Willi syndrome is a neurogenetic disorder characterized by hypotonia and feeding difficulties in infancy, followed by hyperphagia, hypogonadism, mental retardation, and short stature. It was the first recognized microdeletion syndrome identified with high-resolution chromosome analysis, the first recognized human genomic imprinting disorder, and the first recognized disorder resulting from uniparental disomy. The incidence of Prader–Willi syndrome is approximately 1/10,000–1/15,000 individuals.

Genetics/Basic Defects

  1. 1.
    1. a.

      Usually sporadic events (de novo deletions of 15q11–q13)

    2. b.

      Rare familial transmission (balanced translocations involving 15q11–q13) (<1%)

  2. 2.

    A contiguous gene syndrome involving multiple paternally expressed genes

  3. 3.
    Caused by the lack of expression of normally active paternally inherited genes at chromosome 15q11–q13 because of a phenomenon called genomic imprinting
    1. a.

      The relevant region on chromosome 15q11–q13: normally expressed on the...


Preimplantation Genetic Diagnosis Angelman Syndrome Prenatal Testing Uniparental Disomy Maternal Chromosome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Åkefeldt, A., Törnhage, C. J., & Gillberg, C. (1999). A woman with Prader-Willi syndrome gives birth to a healthy baby girl. Developmental Medicine and Child Neurology, 41, 789–790.PubMedCrossRefGoogle Scholar
  2. American academy of Pediatrics Committee on Genetics. (2011). Health supervision of children with Prader-Willi syndrome. Pediatrics, 127, 195–204.CrossRefGoogle Scholar
  3. American Society for Human Genetics. (1996). Diagnostic testing for Prader-Willi and Angelman syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee. American Journal of Human Genetics, 58, 1085–1088.Google Scholar
  4. Ashley, C. T., Jr., & Warren, S. T. (1995). Trinucleotide repeat expansion and human disease. Annual Review of Genetics, 29, 703–728.PubMedCrossRefGoogle Scholar
  5. Aughton, D. J., & Cassidy, S. B. (1990). Physical features of Prader-Willi syndrome in neonates. American Journal of Diseases of Children, 144, 1251–1254.PubMedGoogle Scholar
  6. Brannan, C. I., & Bartolomei, M. S. (1999). Mechanisms of genomic imprinting. Current Opinion in Genetics and Development, 9, 164–170.PubMedCrossRefGoogle Scholar
  7. Bray, G., Dahms, W., Swerdloff, R., et al. (1983). The Prader-Willi syndrome: A study of 40 patients and a review of the literature. Medicine, 62, 59–80.PubMedCrossRefGoogle Scholar
  8. Buiting, K. (2010). Prader-Willi syndrome and Angelman syndrome. American Journal of Medical Genetics. Part C Seminars in Medical Genetics, 154C, 365–376.CrossRefGoogle Scholar
  9. Buiting, K., Dittrich, B., Gross, S., et al. (1998). Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis. American Journal of Human Genetics, 63, 170–180.PubMedCrossRefGoogle Scholar
  10. Buiting, K., Farber, C., Kroisel, P., et al. (2000). Imprinting center in two PWS families: Implications for diagnostic testing and genetic counseling. Clinical Genetics, 58, 284–290.PubMedCrossRefGoogle Scholar
  11. Buiting, K., Gross, S., Lich, C., et al. (2003). Epimutations in Prader-Willi and Angelman syndromes: A molecular study of 136 patients with an imprinting defect. American Journal of Human Genetics, 72, 571–577.PubMedCrossRefGoogle Scholar
  12. Buiting, K., Saitoh, S., Gross, S., et al. (1994). Inherited microdeletions in the Angelman and Prader-Willi syndrome define an imprinting centre on human chromosome 15. Nature Genetics, 9, 395–400.CrossRefGoogle Scholar
  13. Burd, L., Vesely, B., Martsolf, J., et al. (1990). Prevalence study of Prader-Willi syndrome in North Dakota. American Journal of Medical Genetics, 37, 97–99.PubMedCrossRefGoogle Scholar
  14. Butler, M. G. (1996). Molecular diagnosis of Prader-Willi syndrome: Comparison of cytogenetic and molecular genetic data including parent of origin dependent methylation DNA patterns. American Journal of Medical Genetics, 61, 188–190.PubMedCrossRefGoogle Scholar
  15. Butler, M. G., & Palmer, C. G. (1983). Parental origin of chromosome 15 deletion in Prader-Willi syndrome. Lancet, 1, 1285–1286.PubMedCrossRefGoogle Scholar
  16. Buttler, M. G. (1990). Prader-Willi syndrome: Current understanding of cause and diagnosis. American Journal of Medical Genetics, 35, 319–332.CrossRefGoogle Scholar
  17. Cassidy, S. B. (1984). Prader-Willi syndrome. Current Problems in Pediatrics, 14, 1–55.PubMedCrossRefGoogle Scholar
  18. Cassidy, S. B. (1987). Recurrence risk in Prader-Willi syndrome. American Journal of Medical Genetics, 28, 59–60.PubMedCrossRefGoogle Scholar
  19. Cassidy, S. B. (1994). Aging in Prader-Willi syndrome: 22 patients over age 30 years. Proceedings of the Greenwood GeneticsCenter, 13, 102–103.Google Scholar
  20. Cassidy, S. B. (1997). Prader-Willi syndrome. Journal of Medical Genetics, 34, 917–923.PubMedCrossRefGoogle Scholar
  21. Cassidy, S. B. (2000). Prader-Willi and Angelman syndromes: Sister imprinted disorders. American Journal of Medical Genetics, 97, 136–146.PubMedCrossRefGoogle Scholar
  22. Cassidy, S. B. (2001). Prader-Willi syndrome. In S. B. Cassidy & J. E. Allanson (Eds.), Management of genetic syndromes. New York: Wiley-Liss.Google Scholar
  23. Cassidy, S. B., & Driscoll, D. J. (2009). Prader-Willi syndrome. European Journal of Human Genetics, 17, 3–13.PubMedCrossRefGoogle Scholar
  24. Cassidy, S. B., & Schwartz, S. (1998). Prader-Willi and Angelman syndromes: Disorders of genomic imprinting. Medicine, 77, 140–151.PubMedCrossRefGoogle Scholar
  25. Cassidy, S. B., Schwartz, S. (2009). Prader-Willi syndrome. GeneReviews. Updated September 3, 2009. Available at:
  26. Christian, S. L., Smith, A. C. M., Macha, M., et al. (1996). Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism. Prenatal Diagnosis, 16, 323–332.PubMedCrossRefGoogle Scholar
  27. Curfs, L. M., & Fryns, J. P. (1992). Prader-Willi syndrome: A review with special attention to the cognitive and behavioral profile. Birth Defects Original Article Series, 28, 99–104.PubMedGoogle Scholar
  28. Delach, J. A., Rosengren, S. S., Kaplan, L., et al. (1994). Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and Angelman syndrome. American Journal of Medical Genetics, 52, 85–91.PubMedCrossRefGoogle Scholar
  29. Driscoll, D. J., Waters, M. F., Williams, C. A., et al. (1992). A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics, 13, 917–924.PubMedCrossRefGoogle Scholar
  30. Dykens, E. M., Cassidy, S. B., & King, B. H. (1996). Prader-Willi syndrome: Genetic, behavioral and treatment issues. Child and Adolescent Clinics of North America, 5, 913–927.Google Scholar
  31. Dykens, E. M., Leckman, J. F., & Cassidy, S. B. (1996). Obsessions and compulsions in Prader-Willi syndrome. Journal of Child Psychology and Psychiatry, 37, 995–1002.PubMedCrossRefGoogle Scholar
  32. Einfeld, S. L., Smith, A., Durvasula, S., et al. (1999). Behavior and emotional disturbance in Prader-Willi syndrome. American Journal of Medical Genetics, 82, 123–127.PubMedCrossRefGoogle Scholar
  33. European Collaborative Research on Mosaicism in CVS. (1999). Trisomy 15 CPM: Probable origins, pregnancy outcome and risk of fetal UPD. Prenatal Diagnosis, 19, 29–35.CrossRefGoogle Scholar
  34. Everman, D. B., & Cassidy, S. B. (2000). Genetics of childhood disorders: XII. Genomic imprinting: breaking the rules. Journal of the American Academy of Child Adolescent Psychiatry, 39, 386–389.CrossRefGoogle Scholar
  35. Fridman, C. (2000). Origin of uniparental disomy 15 in patients with Prader-Willi or Angelman syndrome. American Journal of Medical Genetics, 94, 249–253.PubMedCrossRefGoogle Scholar
  36. Gillessen-Kaesbach, G., Gross, S., Kaya-Westerloh, S., et al. (1995). DNA methylation based testing of 450 patients suspected of having Prader-Willi syndrome. Journal of Medical Genetics, 32, 88–92.PubMedCrossRefGoogle Scholar
  37. Glenn, C. C., Deng, G., Michaelis, R. C., et al. (2000). DNA methylation analysis with respect to prenatal diagnosis of the Angelman and Prader-Willi syndromes and imprinting. Prenatal Diagnosis, 20, 300–306.PubMedCrossRefGoogle Scholar
  38. Glenn, C. C., Driscoll, D. J., Yang, T. P., et al. (1997). Genetic imprinting: Potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes. Molecular Human Reproduction, 3, 321–333.PubMedCrossRefGoogle Scholar
  39. Glenn, C. C., Saitoh, S., Jong, M. T., et al. (1996). Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene. American Journal of Human Genetics, 58, 335–346.PubMedGoogle Scholar
  40. Greally, J. M., & State, M. W. (2000). Genetics of childhood disorders: XIII. Genomic imprinting: The indelible mark of the gamete. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 532–535.PubMedCrossRefGoogle Scholar
  41. Greenswag, L. R. (1987). Adults with Prader-Willi syndrome A survey of 22 cases. Developmental Medicine and Child Neurology, 29, 145–152.PubMedCrossRefGoogle Scholar
  42. Greenswag, L. R., & Alexander, R. C. (Eds.). (1995). Management of Prader-Willi syndrome (2nd ed.). New York: Springer.Google Scholar
  43. Hanel, M. L., & Wevrick, R. (2001). The role of genomic imprinting in human developmental disorders: lessons from Prader-Willi syndrome. Clinical Genetics, 59, 156–164.PubMedCrossRefGoogle Scholar
  44. Hart, P. S. (1998). Salivary abnormalities in Prader-Willi syndrome. Annals of the New York Academy of Sciences, 842, 125–131.PubMedCrossRefGoogle Scholar
  45. Hertz, G., Cataletto, M., Feinsilver, S. H., et al. (1995). Developmental trends of sleep-disordered breathing in Prader-Willi syndrome: The role of obesity. American Journal of Medical Genetics, 56, 188–190.PubMedCrossRefGoogle Scholar
  46. Holm, V. A., Cassidy, S. B., Butler, M. G., et al. (1993). Prader-Willi syndrome: Consensus diagnostic criteria. Pediatrics, 91, 398–402.PubMedGoogle Scholar
  47. Holm, V. A., & Pipes, P. L. (1976). Food and children with Prader-Willi syndrome. American Journal of Diseases of Children, 130, 1063–1067.PubMedGoogle Scholar
  48. Horsthemke, B., & Buiting, K. (2006). Imprinting defects on human chromosome 15. Cytogenetic and Genome Research, 113, 292–299.PubMedCrossRefGoogle Scholar
  49. Horsthemke, B., Dittrich, B., & Buiting, K. (1997). Imprinting mutations on human chromosome 15. Human Mutation, 10, 329–337.PubMedCrossRefGoogle Scholar
  50. Hulten, M., Armstrong, S., Challinor, P., et al. (1991). Genomic imprinting in Adv Neurol Angelman and Prader-Willi translocation family. Lancet, 338, 638–639.PubMedCrossRefGoogle Scholar
  51. Kennerknecht, I. (1992). Differentiated recurrence risk estimations in the Prader-Willi syndrome. Clinical Genetics, 41, 303–308.PubMedCrossRefGoogle Scholar
  52. Knoll, J., Nicholls, R., Magenis, R., et al. (1989). Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. American Journal of Medical Genetics, 32, 285–290.PubMedCrossRefGoogle Scholar
  53. Kubota, T., Aradhya, S., Macha, M., et al. (1996). Analysis of parent of origin specific DNA methylation at SNRPN and PW71 in tissues: Implication for prenatal diagnosis. Journal of Medical Genetics, 33, 1011–1014.PubMedCrossRefGoogle Scholar
  54. Kubota, T., Sutcliffe, J. S., Aradhya, S., et al. (1996). Validation studies of SNPRN methylation as a diagnostic test for Prader-Willi syndrome. American Journal of Medical Genetics, 66, 77–80.PubMedCrossRefGoogle Scholar
  55. Kuslich, C. D. (1999). Prader-Willi syndrome is caused by disruption of the SNRPN gene. American Journal of Human Genetics, 64, 70–76.PubMedCrossRefGoogle Scholar
  56. Lai, L. W., Erickson, R. P., & Cassidy, S. B. (1993). Clinical correlates of chromosome 15 deletions and maternal disomy in Prader-Willi syndrome. American Journal of Diseases of Children, 147, 1217–1223.PubMedGoogle Scholar
  57. Lalande, M. (1996). Parental imprinting and human disease. Annual Review of Genetics, 30, 173–195.PubMedCrossRefGoogle Scholar
  58. Le Bris-Quillevere, M. J., Riviere, D., Pluchon-Riviere, E., et al. (1990). Prenatal diagnosis of del(15)(q11q13). Prenatal Diagnosis, 10, 405–411.PubMedCrossRefGoogle Scholar
  59. Ledbetter, D. H., & Engel, E. (1995). Uniparental disomy in humans. Development of an imprinting map and its implications for prenatal diagnosis. Human Molecular Genetics, 4, 1757–1764.PubMedGoogle Scholar
  60. Ledbetter, D., Riccardi, V., Airhart, S., et al. (1981). Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. New England Journal of Medicine, 304, 235–239.CrossRefGoogle Scholar
  61. Lindgren, A. C., Barkeling, B., Hagg, A., et al. (2000). Eating behavior in Prader-Willi syndrome, normal weight, and obese control groups. Journal of Pediatrics, 137, 50–55.PubMedCrossRefGoogle Scholar
  62. Malcolm, S. (1996). Microdeletion and microduplication syndromes. Prenatal Diagnosis, 16, 1213–1219.PubMedCrossRefGoogle Scholar
  63. Mannens, M., & Alders, M. (1999). Genomic imprinting: Concept and clinical consequences. Annals of Medicine, 31, 4–11.PubMedCrossRefGoogle Scholar
  64. Martin, A., State, M., Koenig, K., et al. (1998). Prader-Willi syndrome. The American Journal of Psychiatry, 155, 1265–1273.PubMedGoogle Scholar
  65. Mascari, M. J., Gottlieb, W., Rogan, P. K., et al. (1992). The frequency of uniparental disomy in Prader-Willi syndrome. Implication for molecular diagnosis. New England Journal of Medicine, 326, 1599–1607.PubMedCrossRefGoogle Scholar
  66. McEntagart, M. E., Webb, T., Hardy, C., et al. (2000). Familial Prader-Willi syndrome: Case report and a literature review. Clinical Genetics, 58, 216–223.PubMedCrossRefGoogle Scholar
  67. Miller, S. P., Riley, P., & Shevell, M. I. (1999). The neonatal presentation of Prader-Willi syndrome revisited. Journal of Pediatrics, 134, 226–228.PubMedCrossRefGoogle Scholar
  68. Morison, I. M., & Reeve, A. E. (1998). A catalogue of imprinted genes and parent-of-origin effects in humans and animals. Human Molecular Genetics, 7, 1599–1609.PubMedCrossRefGoogle Scholar
  69. Nicholls, R. D. (1993). Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: A review. American Journal of Medical Genetics, 46, 16–25.PubMedCrossRefGoogle Scholar
  70. Nicholls, R. D. (1994). New insights reveal complex mechanisms involved in genomic imprinting. American Journal of Human Genetics, 54, 733–740 (editorial comment).PubMedGoogle Scholar
  71. Nicholls, R. D., Knoll, J. H., Butler, M. G., et al. (1989). Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature, 342, 281–285.PubMedCrossRefGoogle Scholar
  72. Nicholls, R., Saitoh, S., & Horsthemke, B. (1998). Imprinting in Prader-Willi and Angelman syndromes. Trends in Genetics, 14, 194–200.PubMedCrossRefGoogle Scholar
  73. Ohta, T., Gray, T. A., Rogan, P. K., et al. (1999). Imprinting mutation mechanisms in Prader-Willi syndrome. American Journal of Human Genetics, 64, 397–413.PubMedCrossRefGoogle Scholar
  74. Orstavik, K. H., Tangsrud, S. E., Kiil, R., et al. (1992). Prader-Willi syndrome in a brother and sister without Cytogenetic or detectable molecular genetic abnormality at chromosome 15q11q13. American Journal of Medical Genetics, 44, 534–538.PubMedCrossRefGoogle Scholar
  75. Ozcelik, T., Leff, S., Robinson, W., et al. (1992). Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genetics, 2, 265–269.PubMedCrossRefGoogle Scholar
  76. Prader, A., Labhart, A., & Willi, H. (1956). Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigem Zustand im Neugeborenenalter. Schweiz Med Wschr, 86, 1260–1261.Google Scholar
  77. Reis, A., Dittrich, B., Greger, V., et al. (1994). Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. American Journal of Human Genetics, 54, 741–747.PubMedGoogle Scholar
  78. Ritzen, E. M., Lindgren, A. C., Hagenas, L., et al. (1999). Growth hormone treatment of patients with Prader-Willi syndrome. Swedish Growth Hormone Advisory Group. Journal of Pediatric Endocrinology and Metabolism, 12(Suppl. 1), 345–349.PubMedGoogle Scholar
  79. Roberts, E., Stevenson, K., Cole, T., et al. (1997). Prospective prenatal diagnosis of Prader-Willi syndrome due to maternal disomy for chromosome 15 following trisomic zygote rescue. Prenatal Diagnosis, 17, 780–783.PubMedCrossRefGoogle Scholar
  80. Robinson, W. P., Bottani, A., Yagang, X., et al. (1991). Molecular, cytogenetic and clinical investigations of Prader-Willi syndrome patients. American Journal of Human Genetics, 49, 1219–1234.PubMedGoogle Scholar
  81. Saitoh, S., Buiting, K., Cassidy, S. B., et al. (1997). Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome imprinting mutation patients. American Journal of Medical Genetics, 68, 195–206.PubMedCrossRefGoogle Scholar
  82. Scheimann, A. (2011). Prader-Willi syndrome. Medscape Reference. Updated June 8, 2011. Available at:
  83. Schinzel, A. (1986). Approaches to the prenatal diagnosis of the Prader-Willi syndrome. Human Genetics, 74, 327.PubMedCrossRefGoogle Scholar
  84. Schluter, B., Buschatz, D., Trowitzsch, E., et al. (1997). Respiratory control in children with Prader-Willi syndrome. European Journal of Pediatrics, 156, 65–68.PubMedGoogle Scholar
  85. Schulze, A., Mogensen, H., Hamborg-Petersen, B., et al. (2001). Fertility in Prader-Willi syndrome: A case report with Angelman syndrome in the offspring. Acta Paediatrica, 90, 455–459.PubMedCrossRefGoogle Scholar
  86. Shaffer, L. G., Agan, N., Goldberg, J. D., et al. (2001). American College of Medical Genetics statement of diagnostic testing for uniparental disomy. Genetics in Medicine, 3, 206–211.PubMedCrossRefGoogle Scholar
  87. Slater, H. R., Vaux, C., Pertile, M., et al. (1997). Prenatal diagnosis of Prader-Willi syndrome using PW71 methylation analysis-Uniparental disomy and the significance of residual trisomy 15. Prenatal Diagnosis, 17, 109–113.PubMedCrossRefGoogle Scholar
  88. Smeets, D. F. C. M., Hamel, B. C. J., Nelen, M. R., et al. (1992). Prader-Willi syndrome and Angelman syndrome in cousins from a family with a translocation between chromosomes 6 and 15. The New England Journal of Medicine, 326, 807–811.PubMedCrossRefGoogle Scholar
  89. Soper, R. T., Mason, E. E., Printen, K. J., & Zellweger, H. (1975). Gastric bypass for morbid obesity in children and adolescents. Journal of Pediatric Surgery, 10, 51–58.PubMedCrossRefGoogle Scholar
  90. State, M. W., & Dykens, E. M. (2000). Genetics of childhood disorders: XV. Prader-Willi syndrome: genes, brain, and behavior. Journal of American Academy of Child and Adolescent Psychiatry, 39, 797–800.CrossRefGoogle Scholar
  91. State, M. W., Lombroso, P. J., Pauls, D. L., et al. (2000). The genetics of childhood psychiatric disorders: A decade of progress. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 946–962.PubMedCrossRefGoogle Scholar
  92. Stephenson, J. B. P. (1992). Neonatal presentation of Prader-Willi syndrome in neonates. American Journal of Diseases of Children, 142, 151–152.Google Scholar
  93. Surth, L. C., Wang, H., & Hunter, A. G. W. (1994). Deletion and uniparental disomy involving the same maternal chromosome 15. The New England Journal of Medicine, 330, 572–573.CrossRefGoogle Scholar
  94. Sutcliffe, J. S., Nakao, M., Christian, S., et al. (1994). Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nature Genetics, 8, 52–58.PubMedCrossRefGoogle Scholar
  95. Swaab, D. F., Purba, J. S., & Hofman, M. A. (1995). Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi and “Prader-Willi-like” syndromes: a study of five cases. Journal of Clinical Endocrinology and Metabolism, 80, 573–579.PubMedCrossRefGoogle Scholar
  96. Tauber, M., Diene, G., Molinas, C., et al. (2008). Review of 64 cases of death in children with Prader-Willi syndrome (PWS). American Journal of Medical Genetics. Part A, 146A, 881–887.CrossRefGoogle Scholar
  97. Wevrick, R., & Francke, U. (1996). Diagnostic test for the Prader-Willi syndrome by SNRPN expression in blood. Lancet, 348, 1068–1069.PubMedCrossRefGoogle Scholar
  98. Wharton, R. H., & Loechner, K. J. (1996). Genetic and clinical advances in Prader-Willi syndrome. Current Opinion in Pediatrics, 8, 618–624.PubMedCrossRefGoogle Scholar
  99. Zeschnigk, M., Lich, C., Buiting, K., et al. (1997). A single-tube PCR test for the diagnosis of Angelman and Prader-Willi syndrome based on allelic methylation differences at the SNRPN locus. European Journal of Human Genetics, 5, 94–98.PubMedGoogle Scholar

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