Medscape is available in 5 Language Editions – Choose your Edition here.


Prader-Willi Syndrome

  • Author: Ann Scheimann, MD, MBA; Chief Editor: Luis O Rohena, MD  more...
Updated: Dec 24, 2015


Prader-Willi syndrome (PWS) is a disorder caused by a deletion or disruption of genes in the proximal arm of chromosome 15 or by maternal disomy in the proximal arm of chromosome 15. Commonly associated characteristics of this disorder include diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, strabismus, and small hands and feet.

In 1887, Langdon Down described the first patient with Prader-Willi syndrome as an adolescent girl with mental impairment, short stature, hypogonadism, and obesity and attributed these symptoms to polysarcia.[1] In 1956, Prader et al reported a series of patients with similar phenotypes.[2] In 1981, Ledbetter et al identified deletions located between bands 15q11 and 15q13 and determined it to be the site for Prader-Willi syndrome.[3, 4]



Prader-Willi syndrome is the first human disorder attributed to genomic imprinting. In such disorders, genes are expressed differentially based on the parent of origin. An imprinting center has been identified within 15q11-13; gene expression may be regulated by DNA methylation at cytosine bases.[5] Prader-Willi syndrome results from the loss of imprinted genomic material within the paternal 15q11.2-13 locus. The loss of maternal genomic material at the 15q11.2-13 locus results in Angelman syndrome.[6]

Most cases of Prader-Willi syndrome that involve deletions, unbalanced translocations, and uniparental (maternal) disomy are sporadic. Monozygotic twins are concordantly affected. Approximately 70% of Prader-Willi syndrome cases arise from deletion of band 15q11-13 on chromosome 15. Maternal uniparental disomy caused by chromosomal nondisjunction accounts for 28% of Prader-Willi syndrome cases.[7] Less than 1% of patients have mutations isolated to the imprinting center, which carries a risk of recurrence.[8] Buiting et al have suggested that deletions solely localized to the imprinting center may be due to a failure to erase the maternal imprint during spermatogenesis.[9]

Several genes have been mapped to the 15q11.2-13 region, including the SNRPN gene, P gene (type II oculocutaneous albinism),[10] UBE3A gene (encodes a ubiquitin-protein ligase involved in intracellular protein turnover), and necdin gene (codes for a nuclear protein expressed exclusively in the differentiated mouse brain).[11] Mutations associated with the maternal UBE3A gene result in Angelman syndrome.[9]

The role of ghrelin in the satiety defect found in Prader-Willi syndrome is a subject of active investigation. In 2002, Cummings et al reported significantly elevated ghrelin levels (4.5-fold higher) in individuals with Prader-Willi syndrome.[12] Haqq et al reported improvement in ghrelin levels after octreotide infusion but no significant improvement in postprandial suppression of ghrelin levels.[13] After correction of relative hypoinsulinemia, Goldstone et al reported a residual 1.3-fold to 1.6-fold elevation in fasting ghrelin levels and a 1.2-fold to 1.5-fold elevation in postprandial ghrelin levels in adults with Prader-Willi syndrome.[14]




United States

Most cases of Prader-Willi syndrome are sporadic. Burd et al reported a prevalence rate of 1 per 16,062 population.[15] Butler reported a prevalence rate of 1 per 25,000 population.[16]


Prader-Willi syndrome has been reported worldwide. Reported prevalence rates for Prader-Willi syndrome range from 1 per 8000 population in rural Sweden to 1 per 16,000 population in western Japan.[17, 18] Despite findings that suggest a prevalence rate of 1 per 52,000 population in the United Kingdom, Whittington et al estimate that the actual prevalence rate is higher and propose a true prevalence rate of 1 per 45,000 population.[19]


Complications due to obesity (eg, slipped capital femoral epiphyses, sleep apnea, cor pulmonale, type 2 diabetes mellitus) and behavioral problems are major contributors to morbidity and mortality in individuals with Prader-Willi syndrome (see Complications). Lamb et al reported premature development of atherosclerosis with severe coronary artery disease in an patient aged 26 years with Prader-Willi syndrome, morbid obesity, and non–insulin-dependent diabetes mellitus.[20]

Wharton et al described a series of 6 patients with Prader-Willi syndrome with dramatic acute gastric distention preceded by symptoms of gastroenteritis.[21] One half of the cases rapidly progressed to massive gastric dilatation and gastric necrosis. One patient died of overwhelming sepsis and disseminated intravascular coagulation. Gastric dilatation spontaneously resolved in 2 children. Gastrectomy was performed in 2 patients; in one patient, gastrectomy was subtotal and distal, whereas in the other patient, gastrectomy was combined with partial duodenectomy and pancreatectomy. An autopsy series by Stevenson et al reported gastric rupture and necrosis as the confirmed cause of death in 3% of the patients with Prader-Willi syndrome, with another 4 suspected cases of gastric necrosis.[22]

In a series of 152 patients with Prader-Willi syndrome, choking episodes were reported as the cause of death in 7.9%.[23]

Another series of patients noted 8 children and 2 adults who had unexpected death, with small adrenal glands noted in 3 of 8 children, raising suspicion for underlying adrenal insufficiency.[24] Subsequent studies have disputed the frequency of central adrenal insufficiency proposed by these authors, believing it to be a rare occurrence.[25]


Differences in prevalence rates between racial groups have not been consistently reported. However, in a study of 10 black patients with Prader-Willi syndrome, Hudgins et al (1998) suggested that clinical features in black patients differ from those of white patients.[26] In black patients, growth is less affected, hand lengths are usually normal, and the facies are less typical.


Prader-Willi syndrome is caused by the loss of the paternal copy in the proximal arm of chromosome 15 in the region of 15p11-13. Differences in prevalence rates between sexes have not been reported.


Prader-Willi syndrome is a genetic disorder with lifelong implications.

Contributor Information and Disclosures

Ann Scheimann, MD, MBA Associate Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution

Ann Scheimann, MD, MBA is a member of the following medical societies: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: synageva<br/>Received research grant from: QOL medical, zafgen, FPWR.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Eric T Rush, MD, FAAP, FACMG Clinical Geneticist, Munroe-Meyer Institute for Genetics and Rehabilitation; Assistant Professor of Pediatrics and Internal Medicine, University of Nebraska Medical Center

Eric T Rush, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American College of Physicians, Nebraska Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals<br/>Honoraria for: Alexion Pharmaceuticals and Biomarin Pharmaceuticals.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Michael Fasullo, PhD Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: Radiation Research Society, American Society for Biochemistry and Molecular Biology, Genetics Society of America, Environmental Mutagenesis and Genomics Society

Disclosure: Nothing to disclose.

  1. Down JL. Mental Affections of Childhood and Youth. 1887. 172.

  2. Prader A, Labhart A, Willi H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigem Zustand im Neugeborenenalter. Schweiz Med Wschr. 1956. 86:1260-1.

  3. Ledbetter DH, Engel E. Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Hum Mol Genet. 1995. 4 Spec No:1757-64. [Medline].

  4. Ledbetter DH, Riccardi VM, Airhart SD, et al. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med. 1981 Feb 5. 304(6):325-9. [Medline].

  5. Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989 Nov 16. 342(6247):281-5. [Medline].

  6. Nicholls RD. Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndromes: a review. Am J Med Genet. 1993 Apr 1. 46(1):16-25. [Medline].

  7. Robinson WP, Langlois S, Schuffenhauer S, et al. Cytogenetic and age-dependent risk factors associated with uniparental disomy 15. Prenat Diagn. Sep 1996. 16(9):837-44. [Medline].

  8. Buiting K, Gross S, Lich C, et al. Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am J Hum Genet. 2003 Mar. 72(3):571-7. [Medline].

  9. Buiting K, Saitoh S, Gross S, et al. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nat Genet. 1995 Apr. 9(4):395-400. [Medline].

  10. Rinchik EM, Bultman SJ, Horsthemke B, et al. A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature. 1993 Jan 7. 361(6407):72-6. [Medline].

  11. MacDonald HR, Wevrick R. The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet. 1997 Oct. 6(11):1873-8. [Medline].

  12. Cummings DE, Clement K, Purnell JQ, et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002 Jul. 8(7):643-4. [Medline].

  13. Haqq AM, Stadler DD, Rosenfeld RG, et al. Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader-Willi syndrome. J Clin Endocrinol Metab. Aug 2003. 88(8):3573-6. [Medline].

  14. Goldstone AP, Patterson M, Kalingag N, et al. Fasting and postprandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma. J Clin Endocrinol Metab. 2005 May. 90(5):2681-90. [Medline].

  15. Burd L, Vesely B, Martsolf J, Kerbeshian J. Prevalence study of Prader-Willi syndrome in North Dakota. Am J Med Genet. 1990 Sep. 37(1):97-9. [Medline].

  16. Butler MG. Molecular diagnosis of Prader-Willi syndrome: comparison of cytogenetic and molecular genetic data including parent of origin dependent methylation DNA patterns. Am J Med Genet. 1996 Jan 11. 61(2):188-90. [Medline].

  17. Akefeldt A, Gillberg C, Larsson C. Prader-Willi syndrome in a Swedish rural county: epidemiological aspects. Dev Med Child Neurol. Aug 1991. 33(8):715-21. [Medline].

  18. Ehara H, Ohno K, Takeshita K. Frequency of the Prader-Willi syndrome in the San-in district, Japan. Brain Dev. Sep-Oct 1995. 17(5):324-6. [Medline].

  19. Whittington JE, Holland AJ, Webb T, et al. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet. 2001 Nov. 38(11):792-8. [Medline].

  20. Lamb AS, Johnson WM. Premature coronary artery atherosclerosis in a patient with Prader-Willi syndrome. Am J Med Genet. 1987 Dec. 28(4):873-80. [Medline].

  21. Wharton RH, Wang T, Graeme-Cook F, et al. Acute idiopathic gastric dilation with gastric necrosis in individuals with Prader-Willi syndrome. Am J Med Genet. Dec 31 1997. 73(4):437-41. [Medline].

  22. Stevenson DA, Heinemann J, Angula M, et al. Gastric Rupture and Necrosis in Prader-Willi Syndrome. J Pediatr Gastroenterol Nutr. 2007. 45:272-4. [Medline].

  23. Stevenson DA, Heinemann J, Angulo M, et al. Deaths due to choking in Prader-Willi syndrome. Am J Med Genet A. 2007 Mar 1. 143(5):484-7. [Medline].

  24. Stevenson Da, Anaya TM, Clayton-Smith J, et al. Unexpected Death and Critical Illness in Prader-Willi Syndrome: Report of Ten Individuals. Amer J Med Genet A. 2004. 124A:158-64. [Medline].

  25. Nyunt O, Cotterill AM, Archbold SM, et al. Normal cortisol response on low-dose synacthen (1 microg) test in children with Prader Willi syndrome. J Clin Endocrinol Metab. 2010 Dec. 95(12):E464-7. [Medline].

  26. Hudgins L, Geer JS, Cassidy SB. Phenotypic differerencss in African Americans with Prader-Willi syndrome. Genet Med. 1998 Nov-Dec. 1(1):49-51. [Medline].

  27. Cassidy SB, Schwartz S. Prader-Willi and Angelman syndromes. Disorders of genomic imprinting. Medicine (Baltimore). 1998 Mar. 77(2):140-51. [Medline].

  28. Lee PD. Endocrine and metabolic aspects of Prader-willi syndrome. Greenswag LR, Alexander RC, eds. Management of Prader-willi Syndrome. 2nd ed. New York, NY: Springer-Verlag; 1995. 32-57.

  29. Kaplan J, Fredrickson PA, Richardson JW. Sleep and breathing in patients with the Prader-Willi syndrome. Mayo Clin Proc. 1991 Nov. 66(11):1124-6. [Medline].

  30. Dykens EM, Hodapp RM, Walsh K, Nash LJ. Profiles, correlates, and trajectories of intelligence in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry. Nov 1992. 31(6):1125-30. [Medline].

  31. Greenswag LR. Adults with Prader-Willi syndrome: a survey of 232 cases. Dev Med Child Neurol. 1987 Apr. 29(2):145-52. [Medline].

  32. Martin A, State M, Koenig K, et al. Prader-Willi syndrome. Am J Psychiatry. 1998 Sep. 155(9):1265-73. [Medline].

  33. Soni S, Whittington J, Holland AJ, et al. The Phenomenology and Diagnosis of Psychiatric Illness in People with Prader-Willi Syndrome. Psychol Med. 2008. 38:1505-14. [Medline].

  34. Gito M, Ihara H, Ogata H, et al. Gender Differences in the Behavioral Symptom Severity of Prader-Willi Syndrome. Behav Neurol. 2015. 2015:294127. [Medline].

  35. [Guideline] Holm VA, Cassidy SB, Butler MG, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics. 1993 Feb. 91(2):398-402. [Medline].

  36. Gurd AR, Thompson TR. Scoliosis in Prader-Willi syndrome. J Pediatr Orthop. 1981. 1(3):317-20. [Medline].

  37. ASHG/ACMG Test and Technology Transfer Committee. Diagnostic testing for Prader-Willi and Angleman syndromes. Am J Hum Genet. 1996 May. 58(5):1085-8. [Medline].

  38. Goldstone AP, Holland AJ, Hauffa BP, et al. Recommendations for the Diagnosis and Management of Prader-Willi Syndrome. J Clin Endocrinol Metab. 2008. 93:4183-97. [Medline].

  39. O'Donoghue FJ, Camfferman D, Kennedy JD, et al. Sleep-disordered breathing in Prader-Willi syndrome and its association with neurobehavioral abnormalities. J Pediatr. 2005 Dec. 147(6):832-9. [Medline].

  40. Schluter B, Buschatz D, Trowitzsch E, et al. Respiratory control in children with Prader-Willi syndrome. Eur J Pediatr. Jan 1997. 156(1):65-8. [Medline].

  41. Reychler A. [Cephalometric analysis]. Acta Stomatol Belg. 1976. 73(4):403-21. [Medline].

  42. West LA, Ballock RT. High Incidence of Hip Dysplasia but not Slipped Capital Femoral Epiphysis in Patients With Prader-Willi Syndrome. J Pediatr Orthop. 2004. 24:565-7. [Medline].

  43. Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endcrinol Metabo. 2006 Feb. 91(2):413-7. [Medline].

  44. Pandey SN, Vaidya RA, Irani A. Growth hormone treatment in a girl with Prader Willi syndrome. Indian J Pediatr. Apr 2003. 70(4):351-3. [Medline].

  45. Canadian Agency for Drugs and Technologies in Health. Human Growth Hormone Treatment for Prader-Willi Syndrome in Adolescent and Adult Patients: Clinical Evidence, Safety, and Guidelines. Ottawa, ON: 2015 Nov 06. [Full Text].

  46. Bakker NE, Siemensma EP, van Rijn M, Festen DA, Hokken-Koelega AC. Beneficial Effect of Growth Hormone Treatment on Health-Related Quality of Life in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study. Horm Res Paediatr. 2015. 84 (4):231-9. [Medline].

  47. Soper RT, Mason EE, Printen KJ, Zellweger H. Gastric bypass for morbid obesity in children and adolescents. J Pediatr Surg. 1975 Feb. 10(1):51-8. [Medline].

  48. Scheimann AO, Butler MG, Gourash L, Cuffari C, Klish W. Critical Analysis of Bariatric Procedures in Prader-Willi Syndrome. J Pediatr Gastroenterol Nutr. 2008. 46:80-3. [Medline].

  49. Bistrian BR, Blackburn GL, Stanbury JB. Metabolic Aspects of a Protein-Sparing Modified Fast in the Dietary Management of Prader-Willi Obesity. N Eng J Med. 1977. 296:774-9. [Medline].

  50. Miller JL, Lynn CH, Driscoll DC, et al. Nutritional phases in Prader-Willi syndrome. Am J Med Genet A. 2011 May. 155(5):1040-9. [Medline].

  51. Coppes MJ, Sohl H, Teshima IE, et al. Wilms tumor in a patient with Prader-Willi syndrome. J Pediatr. 1993 May. 122(5 Pt 1):730-3. [Medline].

  52. Jaffray B, Moore L, Dickson AP. Prader-Willi syndrome and intratubular germ cell neoplasia. Med Pediatr Oncol. Jan 1999. 32(1):73-4. [Medline].

  53. Nakajima K, Sakurai A, Kubota T, et al. Multiple endocrine neoplasia type 1 concomitant with Prader-Willi syndrome: case report and genetic diagnosis. Am J Med Sci. 1999 May. 317(5):346-9. [Medline].

  54. Hall BD. Leukaemia and the Prader-Willi syndrome. Lancet. 1985 Jan 5. 1(8419):46. [Medline].

Severe typical scoliosis.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.