Peutz–Jeghers Syndrome

  • Francis M. GiardielloEmail author
Part of the M.D. Anderson Solid Tumor Oncology Series book series (MDA, volume 5)


Peutz-Jeghers Syndrome is an autosomal dominant syndrome characterized by hamartomatous gastrointestinal polyps and mucocutaneous melanin pigmentation. Patients are also at risk for extraintestinal neoplasms. In this chapter, the clinicopathologic characteristics of the syndrome, its management and surveillance recommendations will be discussed.


Autosomal dominant Hamartomatous polyps Melanin pigmentation Intussusception Small bowel polyps 



We are indebted to Ms. Linda Welch for technical support. Supported in part by The John G. Rangos, Sr. Charitable Foundation, The Clayton Fund, and NIH grant 5P50CA062924.


  1. 1.
    Connor JT. Aesculapian society of London. Lancet. 1895;2:1169.Google Scholar
  2. 2.
    Hutchinson J. Pigmentation of the lips and mouth in twin sisters. Arch Surg. 1896;7:290.Google Scholar
  3. 3.
    Peutz JLA. Over een zeer merkwaardige, gecombineerde familiaire polyposis van de slijmvliezen van den tractus intestinalis met die van de neuskeelholte en gepaard met eignaardige pigmentaties van huid en slijmvliezen. Ned Maandschr Geneeskd. 1921;10:134–46.Google Scholar
  4. 4.
    Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips, and digits. A syndrome of diagnostic significance. N Engl J Med. 1949;241:993–1005. 1031–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Bruwer A, Bargen JA, Kieland RR. Surface pigmentation and generalized intestinal polyposis (Peutz–Jeghers syndrome). Mayo Clin Proc. 1954;29:168–71.Google Scholar
  6. 6.
    Weber FP. Patches of deep pigmentation of oral mucus membrane not connected with Addison’s disease. Q J Med. 1949;12:404–8.Google Scholar
  7. 7.
    Giardiello FM, Welsh SB, Offerhaus GJA, Booker SV, Krush AJ, Hamilton SR, et al. Increased risk of cancer in Peutz–Jeghers syndrome. N Engl J Med. 1987;316:1511–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Utsunomiya J, Gocho H, Miyanaga T, Hamaguchi E, Kashimure A, Aoki N, et al. Peutz–Jeghers syndrome: its natural course and management. Johns Hopkins Med J. 1975;136:71–82.PubMedGoogle Scholar
  9. 9.
    Burt RW. Polyposis syndromes. Clin Perspectives Gastro. 2002; 51–59.Google Scholar
  10. 10.
    Kyle J. Peutz–Jeghers syndrome. Scot Med J. 1961;6:361–7.PubMedGoogle Scholar
  11. 11.
    Laugier P, Hunziker N. Pigmentation melanique lenticulaire, essentielle, de la muqueuse jugale et des levres. Arch Bel Dermatol Syphilol. 1970;26:391–9.Google Scholar
  12. 12.
    Boardman LA, Pittelkow MR, Couch FJ, Schaid DJ, McDonnell SK, Burgart LJ, et al. Association of Peutz–Jeghers-like mucocutaneous pigmentation with breast and gynecologic carcinomas in women. Medicine. 2000;79:293–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Giardiello FM. Gastrointestinal polyposis syndromes and hereditary nonpolyposis colorectal cancer. In: Rustgi AK, editor. Gastrointestinal cancers biology diagnosis and therapy. Philadelphia: Lippincott-Raven; 1995. p. 370–1.Google Scholar
  14. 14.
    Dayal Y, DeLellis RA. The gastrointestinal tract. In: Cotran RS, Kumar V, Robbins SL, editors. Robbins pathologic basis of disease. 4th ed. Philadelphia: WB Saunders Company; 1989. p. 827–910.Google Scholar
  15. 15.
    Murday V, Slack J. Inherited disorders associated with colorectal cancer. Cancer. 1989;8:139–57.Google Scholar
  16. 16.
    Keller JJ, Westerman AM, Weterman MA, van Dekken H, Giardiello FM, Rooij FW, et al. Molecular genetic evidence for an association between nasal polyposis and Peutz–Jeghers syndrome. Ann Intern Med. 2002;136:854–5 (letter).CrossRefGoogle Scholar
  17. 17.
    Spigelman AD, Murday V, Phillips RKS. Cancer and the Peutz–Jeghers syndrome. Gut. 1989;30:1588–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Hizawa K, Iida M, Matsumoto T, Kohrogi N, Kinoshita H, Yao T, et al. Cancer in Peutz–Jeghers syndrome. Cancer. 1993;72:2777–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000;19:1447–53.CrossRefGoogle Scholar
  20. 20.
    Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126:1788–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Young RH, Welch WR, Dickersin GR, Scully RE. Ovarian sex cord tumor with annular tubules: review of 74 cases including 27 with Peutz–Jeghers syndrome and 4 with adenoma malignum of the cervix. Cancer. 1982;50:1384–402.PubMedCrossRefGoogle Scholar
  22. 22.
    Solh HM, Azoury RS, Najjar SS. Peutz–Jeghers syndrome associated with precocious puberty. J Pediatr. 1983;103:593–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz–Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18:38–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defect in Peutz–Jeghers syndrome. Nature. 1998;391:184–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Gruber SB, Entius MM, Petersen GM, Laken SJ, Longo PA, Boyer R, et al. Pathogenesis of adenocarcinoma in Peutz–Jeghers syndrome. Cancer Res. 1998;58:5267–70.PubMedGoogle Scholar
  26. 26.
    Ylikorkala A, Avizienyte E, Tomlinson IPM, Tiainen M, Roth S, Loukola A, et al. Mutations and impaired function of LKB1 in familial and non-familial Peutz–Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet. 1999;8:45–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Jansen M, de Leng WW, Baas AF, Weterman MA, Giardiello FM, Offerhaus GJA. Mucosal prolapse in the pathogenesis of Peutz–Jeghers syndrome. Gut. 2006;55:1–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Amos CL, Frazier ML, McGarrity TJ. Peutz–Jeghers syndrome. University of Washington, Seattle. 1993. ( Accessed February 2001.
  29. 29.
    Boardman LA, Couch FJ, Burgart LJ, Schwartz D, Berry R, McDonnell SK, et al. Thibodeau SN Genetic heterogeneity in Peutz–Jeghers syndrome. Hum Mutat. 2000;16:23–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, et al. Genotype–phenotype correlations in Peutz–Jeghers syndrome. J Med Genet. 2004;41:327–33.PubMedCrossRefGoogle Scholar
  31. 31.
    Volikos E, Robinson J, Aittomaki K, Mecklin JP, Jarvinen H, Westerman AM, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz–Jeghers syndrome. J Med Genet. 2006;43:e18.PubMedCrossRefGoogle Scholar
  32. 32.
    Hearle NC, Rudd MF, Lim W, Murday V, Lim AG, Phillips RK, et al. Exonic STK11 deletions are not a rare cause of Peutz–Jeghers syndrome. J Med Genet. 2006;43:e15.PubMedCrossRefGoogle Scholar
  33. 33.
    Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz–Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet. 1998;63:1641–50.PubMedCrossRefGoogle Scholar
  34. 34.
    Tomlinson IP, Oschwang S, Abelovitch D, Nakamura Y, Bodmer WF, Thomas G, et al. Testing candidate loci on chromosomes 1 and 6 for genetic linkage to Peutz–Jeghers’ disease. Ann Hum Genet. 1996;60:377–84.PubMedCrossRefGoogle Scholar
  35. 35.
    Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. STK11 status and intussusception risk in Peutz–Jeghers syndrome. J Med Genet. 2006;43:e41.PubMedCrossRefGoogle Scholar
  36. 36.
    Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. Frequency and spectrum of cancers in the Peutz–Jeghers syndrome. Clin Cancer Res. 2006;12(10):3209–15.PubMedCrossRefGoogle Scholar
  37. 37.
    The Johns Hopkins Guide for Patients and Families. Peutz–Jeghers syndrome. Baltimore, MD: Johns Hopkins University; 2001.Google Scholar
  38. 38.
    McGrath DR, Spigelman AD. Preventive measures in Peutz–Jeghers syndrome. Familial Cancer. 2001;1:121–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Tomlinson IPM, Houlston RS. Peutz–Jeghers syndrome. J Med Genet. 1997;34:1007–11.PubMedCrossRefGoogle Scholar
  40. 40.
    Hinds R, Philp C, Hyer W, Fell JM. Complications of childhood Peutz–Jeghers syndrome: implications for pediatric screening. J Pediatr Gastroenterol Nutr. 2004;39:219–20.PubMedCrossRefGoogle Scholar
  41. 41.
    Giardiello FM, Trimbath JD. Peutz–Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:1550 (letter).CrossRefGoogle Scholar
  42. 42.
    Giardiello FM, Trimbath JD. Peutz–Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408–15.PubMedCrossRefGoogle Scholar
  43. 43.
    Spigelman AD, Arese P, Phillips RKS. Polyposis: the Peutz–Jeghers syndrome. Br J Surg. 1995;82:1311–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Oncel M, Remzi FH, Church JM, Connor JT, Fazio VW. Benefits of ‘clean sweep’ in Peutz–Jeghers patients. Colorectal Dis. 2004;6:332–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Perez-Cuadrado E, Mas P, Hallal H, Shanabo J, Munoz D, Ortega I, et al. Double-balloon enteroscopy: a descriptive study of 50 explorations. Rev Esp Enferm Dig. 2006;98:73–81.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of MedicineThe Johns Hopkins School of MedicineBaltimoreUSA

Personalised recommendations