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Clinical manifestations and diagnosis of familial adenomatous polyposis

Daniel C Chung, MD
Tomer Adar, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Familial adenomatous polyposis (FAP) is characterized by the presence of multiple colorectal adenomatous polyps (typically more than 100). Multiple colorectal adenomas may also be seen in individuals with MUTYH-associated polyposis (MAP). Other rare causes include the polymerase proofreading-associated polyposis (PPAP) syndrome or hereditary mixed polyposis [1].

This topic will review the genetics, clinical manifestations, and diagnosis of FAP. Surveillance strategies for FAP and the clinical features and diagnosis of MUTYH-associated polyposis and the hamartomatous polyposis syndromes are discussed separately. (See "Familial adenomatous polyposis: Screening and management of patients and families" and "MUTYH-associated polyposis" and "Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Juvenile polyposis syndrome" and "PTEN hamartoma tumor syndrome, including Cowden syndrome".)


Familial adenomatous polyposis (FAP) has an estimated prevalence of three cases per 100,000 individuals and accounts for less than 1 percent of all colorectal cancers in the United States [2]. It affects both sexes equally and has a worldwide distribution [3].


Familial adenomatous polyposis (FAP) and its variants are caused by germline mutations in the tumor suppressor gene, Adenomatous Polyposis Coli (APC), located on chromosome 5q21-q22 [4].

FAP follows an autosomal dominant pattern of inheritance with nearly complete penetrance of colonic polyposis but variable penetrance of the extracolonic manifestations of the disease. Up to 25 percent of FAP cases are due to new or de novo APC mutations [5]. Such patients do not have a family history of FAP. (See "Genetics: Glossary of terms" and "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)" and 'Clinical manifestations' below and "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Incomplete or variable penetrance'.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 28, 2017.
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  1. Vasen HF, Tomlinson I, Castells A. Clinical management of hereditary colorectal cancer syndromes. Nat Rev Gastroenterol Hepatol 2015; 12:88.
  2. Wennstrom J, Pierce ER, McKusick VA. Hereditary benign and malignant lesions of the large bowel. Cancer 1974; 34:suppl:850.
  3. Järvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut 1992; 33:357.
  4. Burt RW, DiSario JA, Cannon-Albright L. Genetics of colon cancer: impact of inheritance on colon cancer risk. Annu Rev Med 1995; 46:371.
  5. Bisgaard ML, Fenger K, Bülow S, et al. Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat 1994; 3:121.
  6. Laurent-Puig P, Béroud C, Soussi T. APC gene: database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res 1998; 26:269.
  7. Moisio AL, Järvinen H, Peltomäki P. Genetic and clinical characterisation of familial adenomatous polyposis: a population based study. Gut 2002; 50:845.
  8. Michils G, Tejpar S, Thoelen R, et al. Large deletions of the APC gene in 15% of mutation-negative patients with classical polyposis (FAP): a Belgian study. Hum Mutat 2005; 25:125.
  9. Aretz S, Stienen D, Uhlhaas S, et al. Large submicroscopic genomic APC deletions are a common cause of typical familial adenomatous polyposis. J Med Genet 2005; 42:185.
  10. Leiden Open Variation Database. InSiGHT (International Society for Gastrointestinal Hereditary Tumours), Leiden University Medical Center. Available at: http://chromium.liacs.nl/LOVD2/colon_cancer/ (Accessed on January 17, 2012).
  11. Lamlum H, Papadopoulou A, Ilyas M, et al. APC mutations are sufficient for the growth of early colorectal adenomas. Proc Natl Acad Sci U S A 2000; 97:2225.
  12. Lamlum H, Ilyas M, Rowan A, et al. The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson's 'two-hit' hypothesis. Nat Med 1999; 5:1071.
  13. Giardiello FM, Krush AJ, Petersen GM, et al. Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation. Gastroenterology 1994; 106:1542.
  14. Heinen CD. Genotype to phenotype: analyzing the effects of inherited mutations in colorectal cancer families. Mutat Res 2010; 693:32.
  15. Järvinen HJ, Peltomäki P. The complex genotype-phenotype relationship in familial adenomatous polyposis. Eur J Gastroenterol Hepatol 2004; 16:5.
  16. Giardiello FM, Petersen GM, Piantadosi S, et al. APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis. Gut 1997; 40:521.
  17. Olschwang S, Tiret A, Laurent-Puig P, et al. Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients. Cell 1993; 75:959.
  18. Caspari R, Olschwang S, Friedl W, et al. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 1995; 4:337.
  19. Soravia C, Berk T, Madlensky L, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet 1998; 62:1290.
  20. Davies DR, Armstrong JG, Thakker N, et al. Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene. Am J Hum Genet 1995; 57:1151.
  21. Saurin JC, Ligneau B, Ponchon T, et al. The influence of mutation site and age on the severity of duodenal polyposis in patients with familial adenomatous polyposis. Gastrointest Endosc 2002; 55:342.
  22. Attard TM, Giglio P, Koppula S, et al. Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis. Cancer 2007; 109:761.
  23. Croner RS, Brueckl WM, Reingruber B, et al. Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer 2005; 5:24.
  24. Leoz ML, Carballal S, Moreira L, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet 2015; 8:95.
  25. Petersen GM, Slack J, Nakamura Y. Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology 1991; 100:1658.
  26. 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.
  27. Bussey et al Bussey HJR. Familial Polyposis Coli. Family Studies, Histopathology, Differential Diagnosis and Results of Treatment, Johns Hopkins UniversityPress, Baltimore 1975.
  28. Spirio L, Olschwang S, Groden J, et al. Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993; 75:951.
  29. Brensinger JD, Laken SJ, Luce MC, et al. Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut 1998; 43:548.
  30. Lynch HT, Smyrk T, McGinn T, et al. Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer 1995; 76:2427.
  31. Burt RW, Leppert MF, Slattery ML, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology 2004; 127:444.
  32. Sieber OM, Segditsas S, Knudsen AL, et al. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut 2006; 55:1440.
  33. Hernegger GS, Moore HG, Guillem JG. Attenuated familial adenomatous polyposis: an evolving and poorly understood entity. Dis Colon Rectum 2002; 45:127.
  34. Jagelman DG, DeCosse JJ, Bussey HJ. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1988; 1:1149.
  35. Wallace MH, Phillips RK. Upper gastrointestinal disease in patients with familial adenomatous polyposis. Br J Surg 1998; 85:742.
  36. Burt RW. Gastric fundic gland polyps. Gastroenterology 2003; 125:1462.
  37. Bianchi LK, Burke CA, Bennett AE, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin Gastroenterol Hepatol 2008; 6:180.
  38. Hamilton SR, Bussey HJ, Mendelsohn G, et al. Ileal adenomas after colectomy in nine patients with adenomatous polyposis coli/Gardner's syndrome. Gastroenterology 1979; 77:1252.
  39. Parc YR, Olschwang S, Desaint B, et al. Familial adenomatous polyposis: prevalence of adenomas in the ileal pouch after restorative proctocolectomy. Ann Surg 2001; 233:360.
  40. Primrose JN, Quirke P, Johnston D. Carcinoma of the ileostomy in a patient with familial adenomatous polyposis. Br J Surg 1988; 75:384.
  41. Slowik V, Attard T, Dai H, et al. Desmoid tumors complicating Familial Adenomatous Polyposis: a meta-analysis mutation spectrum of affected individuals. BMC Gastroenterol 2015; 15:84.
  42. Jarrar AM, Milas M, Mitchell J, et al. Screening for thyroid cancer in patients with familial adenomatous polyposis. Ann Surg 2011; 253:515.
  43. Feng X, Milas M, O'Malley M, et al. Characteristics of benign and malignant thyroid disease in familial adenomatous polyposis patients and recommendations for disease surveillance. Thyroid 2015; 25:325.
  44. Tomoda C, Miyauchi A, Uruno T, et al. Cribriform-morular variant of papillary thyroid carcinoma: clue to early detection of familial adenomatous polyposis-associated colon cancer. World J Surg 2004; 28:886.
  45. Groen EJ, Roos A, Muntinghe FL, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol 2008; 15:2439.
  46. Touriño R, Conde-Freire R, Cabezas-Agrícola JM, et al. Value of the congenital hypertrophy of the retinal pigment epithelium in the diagnosis of familial adenomatous polyposis. Int Ophthalmol 2004; 25:101.
  47. Wallis YL, Macdonald F, Hultén M, et al. Genotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expression in familial adenomatous polyposis. Hum Genet 1994; 94:543.
  48. Bertario L, Bandello F, Rossetti C, et al. Congenital hypertrophy of retinal pigment epithelium (CHRPE) as a marker for familial adenomatous polyposis (FAP). Eur J Cancer Prev 1993; 2:69.
  49. Tiret A, Taiel-Sartral M, Tiret E, Laroche L. Diagnostic value of fundus examination in familial adenomatous polyposis. Br J Ophthalmol 1997; 81:755.
  50. GARDNER EJ, RICHARDS RC. Multiple cutaneous and subcutaneous lesions occurring simultaneously with hereditary polyposis and osteomatosis. Am J Hum Genet 1953; 5:139.
  51. Bisgaard ML, Bülow S. Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts. Am J Med Genet A 2006; 140:200.
  52. TURCOT J, DESPRES JP, ST PIERRE F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum 1959; 2:465.
  53. NCCN colorectal cancer screening practice guidelines. National Comprehensive Cancer Network. Oncology (Williston Park) 1999; 13:152.
  54. Burt R, Neklason DW. Genetic testing for inherited colon cancer. Gastroenterology 2005; 128:1696.
  55. American Gastroenterological Association. American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing. Gastroenterology 2001; 121:195.
  56. Vasen HF, Möslein G, Alonso A, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 2008; 57:704.
  57. Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 2001; 121:198.
  58. Rex DK, Johnson DA, Anderson JC, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol 2009; 104:739.
  59. Burt RW, Barthel JS, Dunn KB, et al. NCCN clinical practice guidelines in oncology. Colorectal cancer screening. J Natl Compr Canc Netw 2010; 8:8.
  60. Robson ME, Storm CD, Weitzel J, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 2010; 28:893.
  61. Kastrinos F, Stoffel EM, Balmaña J, Syngal S. Attitudes toward prenatal genetic testing in patients with familial adenomatous polyposis. Am J Gastroenterol 2007; 102:1284.
  62. Church JM. Polymerase proofreading-associated polyposis: a new, dominantly inherited syndrome of hereditary colorectal cancer predisposition. Dis Colon Rectum 2014; 57:396.
  63. Grover S, Kastrinos F, Steyerberg EW, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 2012; 308:485.