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Familial adenomatous polyposis 2(FAP2)

MedGen UID:
474474
Concept ID:
C3272841
Neoplastic Process
Synonyms: Adenomas, multiple colorectal; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; FAP type 2; MUTYH-associated polyposis; MUTYH-related attenuated familial adenomatous polyposis; MYH-associated polyposis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): MUTYH (1p34.1)
 
Monarch Initiative: MONDO:0012041
OMIM®: 608456
Orphanet: ORPHA247798

Disease characteristics

Excerpted from the GeneReview: MUTYH Polyposis
MUTYH polyposis (also referred to as MUTYH-associated polyposis, or MAP) is characterized by a greatly increased lifetime risk of colorectal cancer (CRC). Although typically associated with ten to a few hundred colonic adenomatous polyps, CRC develops in some individuals in the absence of polyposis. Serrated adenomas, hyperplastic/sessile serrated polyps, and mixed (hyperplastic and adenomatous) polyps can also occur. Duodenal adenomas are common, with an increased risk of duodenal cancer. The risk for malignancies of the ovary and bladder is also increased, and there is some evidence of an increased risk for breast and endometrial cancer. Additional reported features include thyroid nodules, benign adrenal lesions, jawbone cysts, and congenital hypertrophy of the retinal pigment epithelium. [from GeneReviews]
Authors:
Maartje Nielsen  |  Elena Infante  |  Randall Brand   view full author information

Additional descriptions

From OMIM
Autosomal recessive colorectal adenomatous polyposis is a disorder characterized by adult-onset of multiple colorectal adenomas and adenomatous polyposis. Affected individuals have a significantly increased risk of colorectal cancer (summary by Sieber et al., 2003). Cheadle and Sampson (2003) reviewed the molecular pathology and biochemistry of MYH colonic polyposis. For a discussion of genetic heterogeneity of FAP, see 175100.  http://www.omim.org/entry/608456
From MedlinePlus Genetics
A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.

In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.  https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis

Clinical features

From HPO
Colon cancer
MedGen UID:
2839
Concept ID:
C0007102
Neoplastic Process
A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.
Adenomatous colonic polyposis
MedGen UID:
358118
Concept ID:
C1868071
Finding
Presence of multiple adenomatous polyps in the colon.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial adenomatous polyposis 2

Suggested Reading

Recent clinical studies

Etiology

Kallenberg FGJ, Bastiaansen BAJ, Nio CY, Soeters MR, Boermeester MA, Aalfs CM, Bossuyt PMM, Dekker E
Dis Colon Rectum 2017 Oct;60(10):1057-1064. doi: 10.1097/DCR.0000000000000809. PMID: 28891849
Peek RM Jr
Cancer Chemother Pharmacol 2004 Sep;54 Suppl 1:S50-6. doi: 10.1007/s00280-004-0887-x. PMID: 15309515
Shah NS, Remzi F, Massmann A, Baixauli J, Fazio VW
Dis Colon Rectum 2003 Jul;46(7):911-7. doi: 10.1007/s10350-004-6684-0. PMID: 12847365
Abrahams NA, Halverson A, Fazio VW, Rybicki LA, Goldblum JR
Dis Colon Rectum 2002 Nov;45(11):1496-502. doi: 10.1097/01.DCR.0000034134.49346.5E. PMID: 12432298
Soravia C, O'Connor BI, Berk T, McLeod RS, Cohen Z
Dis Colon Rectum 1999 Jul;42(7):903-8. doi: 10.1007/BF02237099. PMID: 10411437

Diagnosis

Kallenberg FGJ, Bastiaansen BAJ, Nio CY, Soeters MR, Boermeester MA, Aalfs CM, Bossuyt PMM, Dekker E
Dis Colon Rectum 2017 Oct;60(10):1057-1064. doi: 10.1097/DCR.0000000000000809. PMID: 28891849
Shah NS, Remzi F, Massmann A, Baixauli J, Fazio VW
Dis Colon Rectum 2003 Jul;46(7):911-7. doi: 10.1007/s10350-004-6684-0. PMID: 12847365

Therapy

Peek RM Jr
Cancer Chemother Pharmacol 2004 Sep;54 Suppl 1:S50-6. doi: 10.1007/s00280-004-0887-x. PMID: 15309515
Shah NS, Remzi F, Massmann A, Baixauli J, Fazio VW
Dis Colon Rectum 2003 Jul;46(7):911-7. doi: 10.1007/s10350-004-6684-0. PMID: 12847365

Prognosis

Kallenberg FGJ, Bastiaansen BAJ, Nio CY, Soeters MR, Boermeester MA, Aalfs CM, Bossuyt PMM, Dekker E
Dis Colon Rectum 2017 Oct;60(10):1057-1064. doi: 10.1097/DCR.0000000000000809. PMID: 28891849
Abrahams NA, Halverson A, Fazio VW, Rybicki LA, Goldblum JR
Dis Colon Rectum 2002 Nov;45(11):1496-502. doi: 10.1097/01.DCR.0000034134.49346.5E. PMID: 12432298

Clinical prediction guides

Peek RM Jr
Cancer Chemother Pharmacol 2004 Sep;54 Suppl 1:S50-6. doi: 10.1007/s00280-004-0887-x. PMID: 15309515

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2022
      UK NICE Clinical Guideline CG118, Colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn's disease or adenomas, 2022
    • NICE, 2021
      UK NICE Guideline NG151, Colorectal cancer, 2021
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APC Pathogenic Variants (Familial Adenomatous Polyposis [FAP]), 2019
    • EuroGenetest, 2010
      Clinical utility gene card for: MUTYH-associated polyposis (MAP), autosomal recessive colorectal adenomatous polyposis

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