eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Prader-Willi Syndrome: Differential Diagnoses & Workup

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

Updated: Jul 27, 2009

Differential Diagnoses

Anxiety Disorder: Obsessive-Compulsive Disorder
Obesity
Cryptorchidism
Obesity-Hypoventilation Syndrome and Pulmonary Consequences of Obesity
Failure to Thrive
Obstructive Sleep Apnea Syndrome
Fragile X Syndrome
Osteoporosis
Growth Hormone Deficiency
Short Stature
Hypogonadism
Sleep Apnea

Other Problems to Be Considered

Angelman syndrome
Scoliosis
Hypotonia
Bardet-Biedl syndrome
Cohen syndrome
Albright hereditary osteodystrophy

Workup

Laboratory Studies

  • Genetic testing35,36
    • Genetic testing for Prader-Willi syndrome (PWS) includes chromosomal analysis and assessment for methylation patterns in the Prader-Willi syndrome region.
    • Methylation patterns can be determined with Southern blot hybridization or polymerase chain reaction (PCR) using DNA primers that can detect methylated cytosine.
    • Analysis for underlying uniparental disomy requires samples from both parents and the child with Prader-Willi syndrome.
    • Fluorescent in situ hybridization (FISH) can be used to confirm prenatal diagnosis when a deletion in the 15q region is suspected after chorionic villus sampling or amniocentesis.
    • In a patient with an imprinting center mutation, test both biological parents for the presence of asymptomatic mutations in the imprinting center; such mutations indicate a higher risk for recurrence.
  • Hypogonadism27,36
    • Most patients with Prader-Willi syndrome have hypothalamic dysfunction that manifests as short stature, central obesity, hypogonadism, and osteoporosis.
    • Fasting measurements of serum insulinlike growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) levels are good screening measurements for underlying growth hormone deficiency.
    • Refer patients with diminished growth velocity and abnormal levels of IGF-1 and IGFBP-3 to a pediatric endocrinologist for provocative growth hormone stimulation testing.
    • Assess thyroid and adrenal status in patients when clinically warranted.
    • Hypopituitarism has been reported in some patients with Prader-Willi syndrome.
  • Obesity27,37,38,36
    • Measure glycosylated hemoglobin inpatients with Prader-Willi syndrome who are obese to assess for the development of type 2 diabetes mellitus as clinically warranted, especially if the patient is taking growth hormone supplementation.
    • Evaluate patients with Prader-Willi syndrome for biochemical evidence of pickwickian syndrome (eg, hypercarbia, polycythemia) as clinically warranted.
    • If symptoms suggest sleep apnea or narcolepsy, perform a sleep study with multiple sleep latency testing.

Imaging Studies

  • Individuals with Prader-Willi syndrome are at risk for pathologic fractures secondary to underlying osteoporosis. A high pain tolerance may allow for minimal symptoms of discomfort with obvious deformity. Patients with Prader-Willi syndrome may require the following imaging studies:36
    • MRI of the head (to evaluate for hypopituitarism)
    • Serial dual energy x-ray absorptiometry (DEXA) scanning (for detection and monitoring of osteoporosis)39
    • Scoliosis films

      Severe typical scoliosis.

      Severe typical scoliosis.

      [ CLOSE WINDOW ]
      Severe typical scoliosis.

      Severe typical scoliosis.

    • Chest radiography (if cor pulmonale is suspected)
    • Other imaging modalities as clinically dictated (eg, extremity film for limp evaluation, hip films to screen for hip dysplasia40 )
  • In patients who suddenly develop abdominal distension, abdominal pain, or a decrease in appetite, imaging including plain abdominal radiography, abdominal ultrasonography, or CT scanning and gastrointestinal series may be warranted to screen for possible conditions such as acute gastric dilation, cholelithiasis, or pancreatitis.

Procedures

  • Assess the growth hormone axis and adrenal axis under the supervision of an endocrinologist if clinically warranted.27

More on Prader-Willi Syndrome

Overview: Prader-Willi Syndrome
Differential Diagnoses & Workup: Prader-Willi Syndrome
Treatment & Medication: Prader-Willi Syndrome
Follow-up: Prader-Willi Syndrome
Multimedia: Prader-Willi Syndrome
References
[ CLOSE WINDOW ]

References

  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. Feb 5 1981;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. Nov 16 1989;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. Apr 1 1993;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. Mar 2003;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. Apr 1995;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. Jan 7 1993;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. Oct 1997;6(11):1873-8. [Medline].

  12. Cummings DE, Clement K, Purnell JQ, et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. Jul 2002;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. May 2005;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. Sep 1990;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. Jan 11 1996;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. Nov 2001;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. Dec 1987;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. Mar 1 2007;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. Hudgins L, Geer JS, Cassidy SB. Phenotypic differerencss in African Americans with Prader-Willi syndrome. Genet Med. Nov-Dec 1998;1(1):49-51. [Medline].

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

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

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

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

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

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

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

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

  36. 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].

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

  38. 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].

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

  40. 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].

  41. 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. Feb 2006;91(2):413-7. [Medline].

  42. 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].

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

  44. 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].

  45. 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].

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

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

  48. 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. May 1999;317(5):346-9. [Medline].

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

PWS, Prader-Labhart-Willi syndrome, Prader-Willi syndrome, chromosomal microdeletion, disomy disorder, diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, strabismus, polysarcia, Angelman syndrome, ghrelin, hypoinsulinemia, slipped capital femoral epiphyses, sleep apnea, cor pulmonale, diabetes mellitus type II, obsessive-compulsive behavior, developmental delay, sleep disturbance, hypopigmentation, hypothalamic dysfunction, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

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 and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

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
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert Anthony Saul, MD, Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center
Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.