Skip to main content

Advertisement

SpringerLink
Log in

Small Bowel Polyposis Syndromes

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Intestinal polyposis syndromes are relatively rare. However, it is important for clinicians to recognize the potential risks of these syndromes. Based on histology, these syndromes can be classified mainly into hamartomatous polyposis syndromes and familial adenomatous polyposis (FAP), which affects mainly the large intestine. This review discusses the clinical manifestations and underlying genetics of the most common small intestinal polyposis syndromes: Peutz-Jeghers syndrome (PJS), juvenile polyposis (JP), PTEN hamartoma tumor syndrome (PHTS), and the small intestinal implications of familial adenomatous polyposis (FAP).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene. 2004;23:6445–70.

    Article  PubMed  CAS  Google Scholar 

  2. Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science. 1998;280:1036–7.

    Article  PubMed  CAS  Google Scholar 

  3. Zbuk KM, Eng C. Hamartomatous polyposis syndromes. Nat Clin Pract Gastroenterol Hepatol. 2007;492–502.

  4. Kutscher AH, Zegarelli EV, Rancow RM. Incidence of Peutz-Jeghers syndrome. Am J Dig Dis. 1960;5:576–7.

    Article  PubMed  CAS  Google Scholar 

  5. Utsunomiya J, Gocho H, Miyanaga T, et al. Peutz-Jeghers syndrome: its natural course and management. Johns Hopkins Med J. 1975;136:71–82.

    PubMed  CAS  Google Scholar 

  6. Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408–15.

    Article  PubMed  Google Scholar 

  7. Estrada R, Spjut HJ. Hamartomatous polyps in Peutz-Jeghers syndrome. A light-, histochemical, and electron-microscopic study. Am J Surg Pathol. 1983;7:747–54.

    Article  PubMed  CAS  Google Scholar 

  8. • McGarrity TJ, Amos C. Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci. 2006;63:2135–44. A comprehensive review of the syndrome that includes updated clinical and genetic aspects.

    Article  PubMed  CAS  Google Scholar 

  9. Wang ZJ, Ellis I, Zauber P, et al. Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers’ syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence. J Pathol. 1999;188:9–13.

    Article  PubMed  CAS  Google Scholar 

  10. Volikos E, Robinson J, Automaker K, et al. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet. 2006;43:e18.

    Article  PubMed  CAS  Google Scholar 

  11. Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem. 2006;75:137–63.

    Article  PubMed  CAS  Google Scholar 

  12. Amos CI, Keitheri-Cheteri MB, Sabripour M, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet. 2004;41:327–33.

    Article  PubMed  CAS  Google Scholar 

  13. Sweet K, Willis J, Zhou XP, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294:2465–73.

    Article  PubMed  CAS  Google Scholar 

  14. Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med. 1987;316:1511–4.

    Article  PubMed  CAS  Google Scholar 

  15. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000;119:1447–53.

    Article  PubMed  CAS  Google Scholar 

  16. Lim W, Olschwang S, Keller JJ, et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004;126:1788–94.

    Article  PubMed  CAS  Google Scholar 

  17. Scully RE. Sex cord tumor with annular tubules a distinctive ovarian tumor of the Peutz-Jeghers syndrome. Cancer. 1970;25:1107–21.

    Article  PubMed  CAS  Google Scholar 

  18. Wang ZJ, Ellis I, Zauber P, et al. Allelic imbalance at the LKB1 (STK11) locus in tumors from patients with Peutz-Jeghers’ syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence. J Pathol. 1999;188(1):9–13.

    Article  PubMed  CAS  Google Scholar 

  19. Beggs AD, Latchford AR, Vasen HFA, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59:975–86.

    Article  PubMed  CAS  Google Scholar 

  20. Terauchi S, Snowberger N, Demarco D. Double-balloon endoscopy and Peutz-Jeghers syndrome: a new look at an old disease. Proc (Bayl Univ Med Cent). 2006;19:335–7.

    Google Scholar 

  21. Chow E, Macrae F. A review of juvenile polyposis syndrome. J Gastroenterol Hepatol. 2005;20:1634–40.

    Article  PubMed  CAS  Google Scholar 

  22. Toccalino H, Guastavino E, De Pinni F, et al. Juvenile polyps of the rectum and colon. Acta Paediatr Scand. 1973;62:337–40.

    Article  PubMed  CAS  Google Scholar 

  23. Jass JR, Williams CB, Bussey HJ, et al. Juvenile polyposis—a precancerous condition. Histopathology. 1988;13:619–30.

    Article  PubMed  CAS  Google Scholar 

  24. Bronner MP. Gastrointestinal inherited polyposis syndromes. Mod Pathol. 2003;16(4):359–65.

    Article  PubMed  Google Scholar 

  25. Howe JR, Mitros FA, Summers RW. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol. 1998;5:751–6.

    Article  PubMed  CAS  Google Scholar 

  26. Friedl W, Uhlhaas S, Schulmann K, et al. Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet. 2002;111:108–11.

    Article  PubMed  CAS  Google Scholar 

  27. Schreibman IR, Baker M, Amos C, et al. The hamartomatous polyposis syndromes: a clinical and molecular review. Am J Gastroenterol. 2005;100:476–90.

    Article  PubMed  Google Scholar 

  28. Manfredi M. Hereditary hamartomatous polyposis syndromes: understanding the disease risks as children reach adulthood. Gastroenterol Hepatol (N Y). 2010;6(3):185–96.

    Google Scholar 

  29. Waite KA, Eng C. From developmental disorder to heritable cancer: it’s all in the BMP/TGF-beta family. Nat Rev Genet. 2003;4:763–73.

    Article  PubMed  CAS  Google Scholar 

  30. Grady WM, Myeroff LL, Swinler SE, et al. Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res. 1999;59:320–4.

    PubMed  CAS  Google Scholar 

  31. Sayed MG, Ahmed AF, Ringold JR, et al. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol. 2002;9:901–6.

    Article  PubMed  CAS  Google Scholar 

  32. Brosens LA, Van Hattem A, Hylind LM, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56:965–7.

    Article  PubMed  Google Scholar 

  33. Zbuk KM, Eng C. Cancer phenomics: RET and PTEN as illustrative models. Nat Rev Cancer. 2007;7:35–45.

    Article  PubMed  CAS  Google Scholar 

  34. Nelen MR, van Staveren WC, Peeters EA, et al. Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet. 1997;6:1383–7.

    Article  PubMed  CAS  Google Scholar 

  35. Marra G, Armelao F, Vecchio FM, et al. Cowden’s disease with extensive gastrointestinal polyposis. J Clin Gastroenterol. 1994;18:42–7.

    Article  PubMed  CAS  Google Scholar 

  36. Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000;37:828–30.

    Article  PubMed  CAS  Google Scholar 

  37. Gorlin RJ, Cohen Jr MM, Condon LM, et al. Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet. 1992;44:307–14.

    Article  PubMed  CAS  Google Scholar 

  38. Wiedemann HR, Burgio GR, Aldenhoff P, et al. The proteus syndrome. Partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr. 1983;140:5–12.

    Article  PubMed  CAS  Google Scholar 

  39. Zhou XP, Waite KA, Pulaski R, et al. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet. 2003;73:404–11.

    Article  PubMed  CAS  Google Scholar 

  40. Waite KA, Eng C. Protean PTEN: form and function. Am J Hum Genet. 2002;70:829–44.

    Article  PubMed  CAS  Google Scholar 

  41. Suzuki A, de la Pompa JL, Stambolic V, et al. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol. 1998;8:1169–78.

    Article  PubMed  CAS  Google Scholar 

  42. Sarquis MS, Agrawal S, Shen L, et al. Distinct expression profiles for PTEN transcript and its splice variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. Am J Hum Genet. 2006;79:23–30.

    Article  PubMed  CAS  Google Scholar 

  43. Starink TM, van der Veen JP, Arwert F, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet. 1986;29:222–33.

    Article  PubMed  CAS  Google Scholar 

  44. Marsh DJ, Coulon V, Lunetta KL, et al. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet. 1998;7:507–15.

    Article  PubMed  CAS  Google Scholar 

  45. Whitelaw SC, Murday VA, Tomlinson IP, et al. Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology. 1997;112:327–34.

    Article  PubMed  CAS  Google Scholar 

  46. Jaeger EE, Woodford-Richens KL, Lockett M, et al. An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. Am J Hum Genet. 2003;72:1261–7.

    Article  PubMed  CAS  Google Scholar 

  47. Aretz S, Stienen D, Friedrichs N, et al. Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP). Hum Mutat. 2007;28:985–92.

    Article  PubMed  CAS  Google Scholar 

  48. Bülow S, Björk J, Christensen IJ, et al. DAF Study Group: Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004;53:381–6.

    Article  PubMed  Google Scholar 

  49. Spigelman AD, Williams CB, Talbot IC, et al. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989;2:783–5.

    Article  PubMed  CAS  Google Scholar 

  50. Groves CJ, Saunders BP, Spigelman AD, Phillips RK. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study. Gut. 2002;50:636–41.

    Article  PubMed  CAS  Google Scholar 

  51. Matsumoto T, Esaki M, Yanaru-Fujisawa R, et al. Small-intestinal involvement in familial adenomatous polyposis: evaluation by double-balloon endoscopy and intraoperative enteroscopy. Gastrointest Endosc. 2008;68:911–9.

    Article  PubMed  Google Scholar 

  52. Iaquinto G, Fornasarig M, Quaia M, et al. Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc. 2008;67:61–7.

    Article  PubMed  Google Scholar 

  53. Burke CA, Santisi J, Church J, Levinthal G. The utility of capsule endoscopy small bowel surveillance in patients with polyposis. Am J Gastroenterol. 2005;100:1498–502.

    Article  PubMed  Google Scholar 

  54. Moutou C, Gardes N, Nicod JC, Viville S. Strategies and outcomes of PGD of familial adenomatous polyposis. Mol Hum Reprod. 2007;13:95–101.

    Article  PubMed  CAS  Google Scholar 

  55. Brosens LAA, Keller JJ, Offerhouse GJA, et al. Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut. 2005;54:1034–43.

    Article  PubMed  CAS  Google Scholar 

  56. Aziz O, Athanasiou T, Fazio VW, et al. Meta-analysis of observational studies of ileorectal versus ileal pouch-anal anastomosis for familial adenomatous polyposis. Br J Surg. 2006;93:407–17.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel

    Nadir Arber & Menachem Moshkowitz

Authors
  1. Nadir Arber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Menachem Moshkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadir Arber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arber, N., Moshkowitz, M. Small Bowel Polyposis Syndromes. Curr Gastroenterol Rep 13, 435–441 (2011). https://doi.org/10.1007/s11894-011-0218-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-011-0218-4

Keywords

Search

Navigation