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Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis

Author
Anthony J Lembo, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH

INTRODUCTION

Peutz-Jeghers syndrome (PJS) is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk of gastrointestinal and nongastrointestinal cancer [1-3].

This topic will review the genetic basis, clinical manifestations, and diagnosis of PJS. The management of PJS and other familial hamartomatous polyposis syndromes of the gastrointestinal tract (eg, juvenile polyposis, Cowden syndrome, and Bannayan-Riley Ruvalcaba syndrome) are discussed in detail, separately [4]. (See "Juvenile polyposis syndrome" and "Approach to the patient with colonic polyps".)

EPIDEMIOLOGY AND GENETICS

Peutz-Jeghers syndrome (PJS) is rare with an estimated prevalence of 1:8000 to 1:200,000 births [5]. Males and females are equally affected.

PJS is an autosomal dominant disorder that is most often due to germline mutations in the STK11 (LKB1) gene encoding a serine threonine kinase mapped to chromosome 19p13.3 [6-8]. Germline mutations in STK11, a designated tumor suppressor gene in combination with an acquired genetic defect of the second STK11 allele in somatic cells, are responsible for the clinical manifestations of PJS [7-10]. PJS has a high penetrance of over 90 percent by the age of 30 years, but 10 to 20 percent of individuals with PJS have no family history and are presumed to have PJS due to de novo mutations [11].

STK11 appears to regulate cell polarity, an observation that may be important for explaining how hamartomas develop and the apparent paradox that PJS patients with benign hamartomatous polyps are at increased risk for cancer [12,13]. A traditional theory has been that, for unclear reasons, some hamartomas in patients with PJS proceed on a pathway to malignant transformation. However, an alternative theory suggests that dysregulation of cell polarization leads concurrently to a cancer predisposition while also creating a predisposition for mucosal prolapse [14]. Mucosal prolapse can lead to the development of polypoid lesions that are histologically similar to hamartomas. Thus, the hamartomas seen in PJS may be an epiphenomenon reflecting disruption of cell polarity pathways, which predisposes simultaneously to mucosal prolapse (and hamartoma formation) and cancer.

          

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Literature review current through: Nov 2016. | This topic last updated: Tue Apr 01 00:00:00 GMT 2014.
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References
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  1. 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; 241:1031.
  2. Peutz JL. Over een zeer merkwaardige, gecombineerde familiaire pollyposis van de sligmliezen van den tractus intestinalis met die van de neuskeelholte en gepaard met eigenaardige pigmentaties van huid-en slijmvliezen. Ned Maandschr v Gen 1921; 10:134.
  3. 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, illust; passim.
  4. Harned RK, Buck JL, Sobin LH. The hamartomatous polyposis syndromes: clinical and radiologic features. AJR Am J Roentgenol 1995; 164:565.
  5. Lindor NM, Greene MH. The concise handbook of family cancer syndromes. Mayo Familial Cancer Program. J Natl Cancer Inst 1998; 90:1039.
  6. Olschwang S, Markie D, Seal S, et al. Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J Med Genet 1998; 35:42.
  7. Jenne DE, Reimann H, Nezu J, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998; 18:38.
  8. Hemminki A, Markie D, Tomlinson I, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998; 391:184.
  9. Lim W, Hearle N, Shah B, et al. Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 2003; 89:308.
  10. Boudeau J, Sapkota G, Alessi DR. LKB1, a protein kinase regulating cell proliferation and polarity. FEBS Lett 2003; 546:159.
  11. Hernan I, Roig I, Martin B, et al. De novo germline mutation in the serine-threonine kinase STK11/LKB1 gene associated with Peutz-Jeghers syndrome. Clin Genet 2004; 66:58.
  12. Baas AF, Kuipers J, van der Wel NN, et al. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 2004; 116:457.
  13. Martin SG, St Johnston D. A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. Nature 2003; 421:379.
  14. Jansen M, de Leng WW, Baas AF, et al. Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis. Gut 2006; 55:1.
  15. Volikos E, Robinson J, Aittomäki K, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet 2006; 43:e18.
  16. Mehenni H, Gehrig C, Nezu J, 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.
  17. Hearle N, Lucassen A, Wang R, et al. Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases. Genes Chromosomes Cancer 2004; 41:163.
  18. Wang HH, Xie NN, Li QY, et al. Exome sequencing revealed novel germline mutations in Chinese Peutz-Jeghers syndrome patients. Dig Dis Sci 2014; 59:64.
  19. Utsunomiya J, Gocho H, Miyanaga T, et al. Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J 1975; 136:71.
  20. 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.
  21. van Lier MG, Mathus-Vliegen EM, Wagner A, et al. High cumulative risk of intussusception in patients with Peutz-Jeghers syndrome: time to update surveillance guidelines? Am J Gastroenterol 2011; 106:940.
  22. Cunningham JD, Vine AJ, Karch L, Aisenberg J. The role of laparoscopy in the management of intussusception in the Peutz-Jeghers syndrome: case report and review of the literature. Surg Laparosc Endosc 1998; 8:17.
  23. Haggitt RC, Reid BJ. Hereditary gastrointestinal polyposis syndromes. Am J Surg Pathol 1986; 10:871.
  24. van Lier MG, Wagner A, Mathus-Vliegen EM, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol 2010; 105:1258.
  25. Lim W, Olschwang S, Keller JJ, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 2004; 126:1788.
  26. van Lier MG, Westerman AM, Wagner A, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut 2011; 60:141.
  27. Resta N, Pierannunzio D, Lenato GM, et al. Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study. Dig Liver Dis 2013; 45:606.
  28. Rebsdorf Pedersen I, Hartvigsen A, Fischer Hansen B, et al. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish Polyposis Register. Int J Colorectal Dis 1994; 9:177.
  29. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000; 119:1447.
  30. Perzin KH, Bridge MF. Adenomatous and carcinomatous changes in hamartomatous polyps of the small intestine (Peutz-Jeghers syndrome): report of a case and review of the literature. Cancer 1982; 49:971.
  31. Settaf A, Mansori F, Bargach S, Saidi A. [Peutz-Jeghers syndrome with carcinomatous degeneration of a duodenal hamartomatous polyp]. Ann Gastroenterol Hepatol (Paris) 1990; 26:285.
  32. Defago MR, Higa AL, Campra JL, et al. Carcinoma in situ arising in a gastric hamartomatous polyp in a patient with Peutz-Jeghers syndrome. Endoscopy 1996; 28:267.
  33. Bujanda L, Beguiristain A, Villar JM, et al. [Gastric adenocarcinoma in hamartomatous polyp in Peutz-Jeghers syndrome]. Gastroenterol Hepatol 1996; 19:452.
  34. Entius MM, Westerman AM, Giardiello FM, et al. Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations. Gut 1997; 41:320.
  35. Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987; 316:1511.
  36. Boardman LA, Thibodeau SN, Schaid DJ, et al. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 1998; 128:896.
  37. Srivatsa PJ, Keeney GL, Podratz KC. Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz-Jeghers syndrome. Gynecol Oncol 1994; 53:256.
  38. Young RH, Dickersin GR, Scully RE. A distinctive ovarian sex cord-stromal tumor causing sexual precocity in the Peutz-Jeghers syndrome. Am J Surg Pathol 1983; 7:233.
  39. 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 four with adenoma malignum of the cervix. Cancer 1982; 50:1384.
  40. Wilson DM, Pitts WC, Hintz RL, Rosenfeld RG. Testicular tumors with Peutz-Jeghers syndrome. Cancer 1986; 57:2238.
  41. Young S, Gooneratne S, Straus FH 2nd, et al. Feminizing Sertoli cell tumors in boys with Peutz-Jeghers syndrome. Am J Surg Pathol 1995; 19:50.
  42. Kemmett D, Ellis J, Spencer MJ, Hunter JA. The Laugier-Hunziker syndrome--a clinical review of six cases. Clin Exp Dermatol 1990; 15:111.