Skip to main content
SpringerLink
Log in

Hamartomatous Polyposis Syndromes

  • Chapter
  • First Online:
Hereditary Colorectal Cancer

Abstract

The hamartomatous polyposis syndromes (HPS) include a small but appreciable number of the gastrointestinal hereditary cancer syndromes and are characterized by the presence of gastrointestinal (GI) hamartomatous polyps. Hamartomatous polyps account for a very small percentage of all GI polyps. They arise from excessive proliferation of the epithelial and stromal cells native to the tissue of origin and contain components from any of the three germ layers forming the intestines. The process underlying the progression of hamartomatous polyps to cancer is not fully understood. HPS occur at approximately one tenth of the frequency of adenomatous polyposis syndromes and account for less than 1% of colorectal cancer cases, although their prevalence may be higher than originally thought. It is now well recognized that these syndromes confer a substantial risk of colonic and extracolonic malignancies, therefore making it important to identify individuals with HPS for further risk management.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Schreibman IR, Baker M, Amos C, McGarrity TJ. The Hamartomatous polyposis syndromes - a clinical and molecular review. Am J Gastroenterol. 2005;100:476–90.

    Article  PubMed  Google Scholar 

  2. Ngeow J, Heald B, Rybicki LA, et al. Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps. Gastroenterology. 2013;144:1402–9. https://doi.org/10.1053/j.gastro.2013.02.001.

    Article  CAS  PubMed  Google Scholar 

  3. Jelsig AM. Hamartomatous polyps – a clinical and molecular genetic study. Dan Med J. 2016. https://doi.org/10.1111/cge.12693.

  4. Aretz S. The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes. Dtsch Arztebl Int. 2010;107:163–73. https://doi.org/10.3238/arztebl.2010.0163.

    Article  PubMed  PubMed Central  Google Scholar 

  5. van Lier M, Wagner A, Mathus-Vliegen E, et al. High cancer risk in Peutz–Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105:1258–64. https://doi.org/10.1038/ajg.2009.725.

    Article  PubMed  Google Scholar 

  6. Latchford A, Phillips R. Gastrointestinal polyps and cancer in Peutz-Jeghers syndrome: clinical aspects. Familial Cancer. 2011;10:455–61. https://doi.org/10.1007/s10689-011-9442-1.

    Article  CAS  PubMed  Google Scholar 

  7. Giardiello F, Trimbath J. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408–15. https://doi.org/10.1016/j.cgh.2005.11.005.

    Article  PubMed  Google Scholar 

  8. Entius MM, Westerman AM, Giardiello FM, et al. Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations. Gut. 1997;41:320–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yaguchi T, Wen-Ying L, Hasegawa K, et al. Peutz-Jeghers polyp with several foci of glandular dysplasia: report of a case. Dis Colon Rectum. 1982;25:592–6.

    Article  CAS  PubMed  Google Scholar 

  10. Beggs A, Latchford A, Vasen H, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59:975–86. https://doi.org/10.1136/gut.2009.198499.

    Article  CAS  PubMed  Google Scholar 

  11. Vogel T, Schumacher V, Saleh A, et al. Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe. Int J Color Dis. 2000;15:118–23.

    Article  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. https://doi.org/10.1136/jmg.2003.010900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000;119:1447–53. https://doi.org/10.1053/gast.2000.20228.

    Article  CAS  PubMed  Google Scholar 

  14. Hearle N, Schumacher V, Menko FH, et al. Frequency and Spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006;12:3209–15. https://doi.org/10.1158/1078-0432.CCR-06-0083.

    Article  CAS  PubMed  Google Scholar 

  15. Korsse SE, Harinck F, van Lier MGF, et al. Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance. J Med Genet. 2013;50:59–64. https://doi.org/10.1136/jmedgenet-2012-101277.

    Article  CAS  PubMed  Google Scholar 

  16. Lim W, Olschwang S, Keller JJ, et al. Relative frequency and morphology of cancers in STK11 mutation carriers1 ☆. Gastroenterology. 2004;126:1788–94. https://doi.org/10.1053/j.gastro.2004.03.014.

    Article  CAS  PubMed  Google Scholar 

  17. 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;45:606–11. https://doi.org/10.1016/j.dld.2012.12.018.

    Article  CAS  PubMed  Google Scholar 

  18. Mehenni H, Resta N, Park J-G, et al. Cancer risks in LKB1 germline mutation carriers. Gut. 2006;55:984–90. https://doi.org/10.1136/gut.2005.082990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Korsse SE, Dewint P, Kuipers EJ, van Leerdam ME. Small bowel endoscopy and Peutz-Jeghers syndrome. Best Pract Res Clin Gastroenterol. 2012;26:263–78. https://doi.org/10.1016/j.bpg.2012.03.009.

    Article  PubMed  Google Scholar 

  20. Jelsig AM, Qvist N, Brusgaard K, et al. Hamartomatous polyposis syndromes: a review. Orphanet J Rare Dis. 2014;9:101. https://doi.org/10.1186/1750-1172-9-101.

    Article  PubMed  PubMed Central  Google Scholar 

  21. van Lier M, Mathus-Vliegen E, Wagner A, et al. High cumulative risk of intussusception in patients with Peutz–Jeghers syndrome: time to update surveillance guidelines? Am J Gastroenterol. 2011;106:940–5. https://doi.org/10.1038/ajg.2010.473.

    Article  PubMed  Google Scholar 

  22. Goldstein SA, Hoffenberg EJ. Peutz-Jegher syndrome in childhood. J Pediatr Gastroenterol Nutr. 2013;56:191–5. https://doi.org/10.1097/MPG.0b013e318271643c.

    Article  PubMed  Google Scholar 

  23. Brown G, Fraser C, Schofield G, et al. Video capsule endoscopy in Peutz-Jeghers syndrome: a blinded comparison with barium follow-through for detection of small-bowel polyps. Endoscopy. 2006;38:385–90. https://doi.org/10.1055/s-2006-925028.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta A, Postgate AJ, Burling D, et al. A prospective study of MR Enterography versus capsule endoscopy for the surveillance of adult patients with Peutz-Jeghers syndrome. Am J Roentgenol. 2010;195:108–16. https://doi.org/10.2214/AJR.09.3174.

    Article  Google Scholar 

  25. Aretz S, Stienen D, Uhlhaas S, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26:513–9. https://doi.org/10.1002/humu.20253.

    Article  CAS  PubMed  Google Scholar 

  26. Papp J, Kovacs ME, Solyom S, et al. High prevalence of germline STK11 mutations in Hungarian Peutz-Jeghers syndrome patients. BMC Med Genet. 2010;11:169. https://doi.org/10.1186/1471-2350-11-169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mehenni H, Resta N, Guanti G, et al. Molecular and clinical characteristics in 46 families affected with Peutz–Jeghers syndrome. Dig Dis Sci. 2007;52:1924–33. https://doi.org/10.1007/s10620-006-9435-3.

    Article  CAS  PubMed  Google Scholar 

  28. Plawski A, Cichy W, Klincewicz B. Juvenile polyposis syndrome. Arch Med Sci. 2014;10:570–7. https://doi.org/10.5114/aoms.2014.43750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen H-M, Fang J-Y. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Color Dis. 2009;24:865–74. https://doi.org/10.1007/s00384-009-0714-2.

    Article  Google Scholar 

  30. Latchford A, Neale K, Phillips R, Clark S. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum. 2012;55:1038–43. https://doi.org/10.1097/DCR.0b013e31826278b3.

    Article  PubMed  Google Scholar 

  31. Brosens LA, Langeveld D, Arnout W, et al. Juvenile polyposis syndrome. World J Gastroenterol. 2011;17:4839–44. https://doi.org/10.3748/wjg.v17.i44.4839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kapetanakis A, Vini D, Plitsis G. Solitary juvenile polyps in children and colon cancer. Hepato-Gastroenterology. 1996;43:1530–1.

    CAS  PubMed  Google Scholar 

  33. Nugent KP, Talbot IC, Hodgson SV, Phillips RK. Solitary juvenile polyps: not a marker for subsequent malignancy. Gastroenterology. 1993;105:698–700.

    Article  CAS  PubMed  Google Scholar 

  34. Coburn M, Pricolo V, DeLuca F, Bland K. Malignant potential in intestinal juvenile polyposis syndromes. Ann Surg Oncol. 1995;2:386–91.

    Article  CAS  PubMed  Google Scholar 

  35. Sachatello CR, Griffen WO. Hereditary polypoid diseases of the gastrointestinal tract: a working classification. Am J Surg. 1975;129:198–203.

    Article  CAS  PubMed  Google Scholar 

  36. Sachatello CR, Hahn IS, Carrington CB. Juvenile gastrointestinal polyposis in a female infant: report of a case and review of the literature of a recently recognized syndrome. Surgery. 1974;75:107–14.

    CAS  PubMed  Google Scholar 

  37. Alimi A, Weeth-Feinstein LA, Stettner A, et al. Overlap of juvenile polyposis syndrome and cowden syndrome due to de novo chromosome 10 deletion involving BMPR1A and PTEN: implications for treatment and surveillance. Am J Med Genet. 2015;167:1305–8. https://doi.org/10.1002/ajmg.a.36876.

    Article  CAS  PubMed  Google Scholar 

  38. Delnatte C, Sanlaville D, Mougenot J-F, et al. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet. 2006;78:1066–74. https://doi.org/10.1086/504301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Menko F, Kneepkens C, De Leeuw N, et al. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes. Clin Genet. 2008;74:145–54. https://doi.org/10.1111/j.1399-0004.2008.01026.x.

    Article  CAS  PubMed  Google Scholar 

  40. Merg A, Howe JR. Genetic conditions associated with intestinal juvenile polyps. Am J Med Genet. 2004;129:44–55. https://doi.org/10.1002/ajmg.c.30020.

    Article  Google Scholar 

  41. Desai D, Murday V, Phillips R, et al. A survey of phenotypic features in juvenile polyposis. J Med Genet. 1998;35:476–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Aytac E, Sulu B, Heald B, et al. Genotype-defined cancer risk in juvenile polyposis syndrome. Br J Surg. 2015;102:114–8. https://doi.org/10.1002/bjs.9693.

    Article  CAS  PubMed  Google Scholar 

  43. 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. https://doi.org/10.1007/s00439-002-0748-9.

    Article  CAS  PubMed  Google Scholar 

  44. Aretz S, Stienen D, Uhlhaas S, et al. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet. 2007;44:702–9. https://doi.org/10.1136/jmg.2007.052506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. O’Malley M, LaGuardia L, Kalady MF, et al. The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum. 2012;55:886–92. https://doi.org/10.1097/DCR.0b013e31825aad32.

    Article  PubMed  Google Scholar 

  46. Jass J, Williams C, Bussey H, Morson B. Juvenile polyposis--a precancerous condition. Histopathology. 1988;13:619–30.

    Article  CAS  PubMed  Google Scholar 

  47. Brosens LA, van Hattem A, Hylind LM, et al. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56:965–7. https://doi.org/10.1136/gut.2006.116913.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Howe J, Mitros F, Summers R. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol. 1998;5:751–6.

    Article  CAS  PubMed  Google Scholar 

  49. Ma C, Giardiello FM, Montgomery EA. Upper tract juvenile polyps in juvenile polyposis patients: dysplasia and malignancy are associated with foveolar, intestinal, and pyloric differentiation. Am J Surg Pathol. 2014;38:1618–26. https://doi.org/10.1097/PAS.0000000000000283.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Walpole IR, Cullity G, Opitz JM, Reynolds JF. Juvenile polyposis: a case with early presentation and death attributable to adenocarcinoma of the pancreas. Am J Med Genet. 1989;32:1–8. https://doi.org/10.1002/ajmg.1320320102.

    Article  CAS  PubMed  Google Scholar 

  51. Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59:666–89. https://doi.org/10.1136/gut.2009.179804.

    Article  PubMed  Google Scholar 

  52. Syngal S, Brand RE, Church JM, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110:223–62. https://doi.org/10.1038/ajg.2014.435.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Faughnan M, Palda V, Garcia-Tsao G, et al. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. J Med Genet. 2011;48:73–87. https://doi.org/10.1136/jmg.2009.069013.

    Article  CAS  PubMed  Google Scholar 

  54. Howe J, Sayed M, Ahmed A, et al. The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet. 2004;41:484–91. https://doi.org/10.1136/jmg.2004.018598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Daly MB, Pilarski R, Axilbund J, et al. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment:Breast and Ovarian, Version 2.2017 J Natl Compr Canc Netw 2017;15:9–20 doi:10.6004/jnccn.2017.0003.

    Article  Google Scholar 

  56. Bannayan G. Lipomatosis, angiomatosis, and macrencephalia. A previously undescribed congenital syndrome. Arch Pathol. 1971;92:1–5.

    CAS  PubMed  Google Scholar 

  57. Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000;37:828–30. https://doi.org/10.1136/jmg.37.11.828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ngeow J, Eng C. PTEN hamartoma tumor syndrome: clinical risk assessment and management protocol. Methods. 2015;77–78:11–9. https://doi.org/10.1016/j.ymeth.2014.10.011.

    Article  CAS  PubMed  Google Scholar 

  59. Nelen MR, Padberg GW, Peeters EAJ, et al. Localization of the gene for Cowden disease to chromosome 10q22–23. Nat Genet. 1996;13:114–6. https://doi.org/10.1038/ng0596-114.

    Article  CAS  PubMed  Google Scholar 

  60. Uppal S, Mistry D, Coatesworth A. Cowden disease: a review. Int J Clin Pract. 2007;61:645–52. https://doi.org/10.1111/j.1742-1241.2006.00896.x.

    Article  CAS  PubMed  Google Scholar 

  61. Coriat R, Mozer M, Caux E, et al. Endoscopic findings in Cowden syndrome. Endoscopy. 2011;43:723–6. https://doi.org/10.1055/s-0030-1256342.

    Article  CAS  PubMed  Google Scholar 

  62. Heald B, Mester J, Rybicki L, et al. Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology. 2010;139:1927–33. https://doi.org/10.1053/j.gastro.2010.06.061.

    Article  CAS  PubMed  Google Scholar 

  63. Levi Z, Baris HN, Kedar I, et al. Upper and lower gastrointestinal findings in PTEN mutation-positive Cowden syndrome patients participating in an active surveillance program. Clin Transl Gastroenterol. 2011;2:e5. https://doi.org/10.1038/ctg.2011.4.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Stanich PP, Owens VL, Sweetser S, et al. Colonic polyposis and neoplasia in Cowden syndrome. Mayo Clin Proc. 2011;86:489–92. https://doi.org/10.4065/mcp.2010.0816.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Tan M-H, Mester J, Peterson C, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011;88:42–56. https://doi.org/10.1016/j.ajhg.2010.11.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bubien V, Bonnet F, Brouste V, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med Genet. 2013;50:255–63. https://doi.org/10.1136/jmedgenet-2012-101339.

    Article  CAS  PubMed  Google Scholar 

  67. Ngeow J, Mester J, Rybicki LA, et al. Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations. J Clin Endocrinol Metab. 2011;96:E2063–71. https://doi.org/10.1210/jc.2011-1616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nieuwenhuis MH, Kets CM, Murphy-Ryan M, et al. Cancer risk and genotype–phenotype correlations in PTEN hamartoma tumor syndrome. Familial Cancer. 2014;13:57–63. https://doi.org/10.1007/s10689-013-9674-3.

    Article  CAS  PubMed  Google Scholar 

  69. Tan M, Mester J, Ngeow J, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res. 2012;18:400–7. https://doi.org/10.1158/1078-0432.CCR-11-2283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sherman SK, Maxwell JE, Qian Q, et al. Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations. Cancer Genet. 2015;208:41–6. https://doi.org/10.1016/j.cancergen.2014.11.002.

    Article  CAS  PubMed  Google Scholar 

  71. NCCN. Genetic/familial high-risk assessment: breast and ovarian. Natl Compr Cancer Netw. 2016.

    Google Scholar 

  72. Ngeow J, Liu C, Zhou K, et al. Detecting germline PTEN mutations among at-risk patients with cancer: an age- and sex-specific cost-effectiveness analysis. J Clin Oncol. 2015;33:2537–44. https://doi.org/10.1200/JCO.2014.60.3456.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ngeow J, Stanuch K, Mester JL, et al. Second malignant neoplasms in patients with Cowden syndrome with underlying germline PTEN mutations. J Clin Oncol. 2014;32:1818–24. https://doi.org/10.1200/JCO.2013.53.6656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gorlin RJ, Cohen MM, Condon LM, Burke BA. Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet. 1992;44:307–14. https://doi.org/10.1002/ajmg.1320440309.

    Article  CAS  PubMed  Google Scholar 

  75. Marsh D, Kum J, Lunetta K, et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet. 1999;8:1461–72.

    Article  CAS  PubMed  Google Scholar 

  76. Mester J, Eng C. Estimate of de novo mutation frequency in probands with PTEN hamartoma tumor syndrome. Genet Med. 2012;14:819–22. https://doi.org/10.1038/gim.2012.51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ni Y, He X, Chen J, et al. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. 2012;21:300–10. https://doi.org/10.1093/hmg/ddr459.

    Article  CAS  PubMed  Google Scholar 

  78. Ni Y, Zbuk KM, Sadler T, et al. Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. Am J Hum Genet. 2008;83:261–8. https://doi.org/10.1016/j.ajhg.2008.07.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nizialek EA, Mester JL, Dhiman VK, et al. KLLN epigenotype-phenotype associations in Cowden syndrome. Eur J Hum Genet. 2015;23:1538–43. https://doi.org/10.1038/ejhg.2015.8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Colby S, Yehia L, Niazi F, et al. Exome sequencing reveals germline gain-of-function EGFR mutation in an adult with Lhermitte-Duclos disease. Cold Spring Harb Mol Case Stud. 2016;2:a001230. https://doi.org/10.1101/mcs.a001230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yehia L, Niazi F, Ni Y, et al. Germline heterozygous variants in SEC23B are associated with Cowden syndrome and enriched in apparently sporadic thyroid cancer. Am J Hum Genet. 2015;97:661–76. https://doi.org/10.1016/j.ajhg.2015.10.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ni Y, Seballos S, Fletcher B, et al. Germline compound heterozygous poly-glutamine deletion in USF3 may be involved in predisposition to heritable and sporadic epithelial thyroid carcinoma. Hum Mol Genet. ddw382. 2016. https://doi.org/10.1093/hmg/ddw382.

  83. Schwartz R. Basal-cell-nevus syndrome and gastrointestinal polyposis. N Engl J Med. 1978;299:49. https://doi.org/10.1056/NEJM197807062990118.

    Article  CAS  PubMed  Google Scholar 

  84. Plesec T, Brown K, Allen C, et al. Clinicopathological features of a kindred with SCG5-GREM1–associated hereditary mixed polyposis syndrome. Hum Pathol. 2017;60:75–81. https://doi.org/10.1016/j.humpath.2016.10.002.

    Article  CAS  PubMed  Google Scholar 

  85. Jaeger E, Leedham S, Lewis A, et al. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet. 2012;44:699–703. https://doi.org/10.1038/ng.2263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Thomas HJ, Whitelaw SC, Cottrell SE, et al. Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q. Am J Hum Genet. 1996;58:770–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Cao X, Eu KW, Kumarasinghe MP, et al. Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet. 2006;43:e13. https://doi.org/10.1136/jmg.2005.034827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. O’Riordan JM, O’Donoghue D, Green A, et al. Hereditary mixed polyposis syndrome due to a BMPR1A mutation. Color Dis. 2009;12:570–3. https://doi.org/10.1111/j.1463-1318.2009.01931.x.

    Article  Google Scholar 

  89. Agaimy A, Vassos N, Croner RS. Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen’s disease): clinicopathological spectrum with pathogenetic considerations. Int J Clin Exp Pathol. 2012;5:852–62.

    PubMed  PubMed Central  Google Scholar 

  90. Moline J, Eng C. Multiple endocrine neoplasia type 2: an overview. Genet Med. 2011;13:755–64. https://doi.org/10.1097/GIM.0b013e318216cc6d.

    Article  CAS  PubMed  Google Scholar 

  91. Uusitalo E, Rantanen M, Kallionpää RA, et al. Distinctive cancer associations in patients with Neurofibromatosis type 1. J Clin Oncol. 2016;34:1978–86. https://doi.org/10.1200/JCO.2015.65.3576.

    Article  PubMed  Google Scholar 

  92. Walker L, Thompson D, Easton D, et al. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br J Cancer. 2006;95:233–8. https://doi.org/10.1038/sj.bjc.6603227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid. 2015;25:567–610. https://doi.org/10.1089/thy.2014.0335.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Disclosure of Potential Conflict of Interest

No author had any relevant financial or personal relationships that could inappropriately influence or bias this work.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, National Cancer Centre, Singapore, Singapore

    Joanne Ngeow & Eliza Courtney

  2. Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore

    Joanne Ngeow

  3. Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA

    Joanne Ngeow & Charis Eng

  4. Division of Pathology, Singapore General Hospital, Singapore, Singapore

    Kiat Hon Lim

  5. Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Charis Eng

  6. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Charis Eng

  7. Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Charis Eng

  8. Germline High Risk Focus Group, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Charis Eng

Authors
  1. Joanne Ngeow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eliza Courtney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiat Hon Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charis Eng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charis Eng .

Editor information

Editors and Affiliations

  1. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Laura Valle

  2. University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Stephen B. Gruber

  3. Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona, Spain

    Gabriel Capellá

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ngeow, J., Courtney, E., Lim, K.H., Eng, C. (2018). Hamartomatous Polyposis Syndromes. In: Valle, L., Gruber, S., Capellá, G. (eds) Hereditary Colorectal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-74259-5_13

Download citation

Publish with us

Policies and ethics

Search

Navigation