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Familial adenomatous polyposis 1(FAP1)

MedGen UID:
398651
Concept ID:
C2713442
Disease or Syndrome
Synonyms: APC-Associated Polyposis Conditions; Colon Cancer (APC I1307K related); FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; FAP1; POLYPOSIS, ADENOMATOUS INTESTINAL
 
Gene (location): APC (5q22.2)
 
Monarch Initiative: MONDO:0021056
OMIM®: 175100

Disease characteristics

Excerpted from the GeneReview: APC-Associated Polyposis Conditions
APC-associated polyposis conditions include (classic or attenuated) familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP is a colorectal cancer (CRC) predisposition syndrome that can manifest in either classic or attenuated form. Classic FAP is characterized by hundreds to thousands of adenomatous colonic polyps, beginning on average at age 16 years (range 7-36 years). For those with the classic form of FAP, 95% of individuals have polyps by age 35 years; CRC is inevitable without colectomy. The mean age of CRC diagnosis in untreated individuals is 39 years (range 34-43 years). The attenuated form is characterized by multiple colonic polyps (average of 30), more proximally located polyps, and a diagnosis of CRC at a later age than in classic FAP. For those with an attenuated form, there is a 70% lifetime risk of CRC and the mean age of diagnosis is 50-55 years. Extracolonic manifestations are variably present and include polyps of the stomach and duodenum, osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoid tumors, adrenal masses, and other associated cancers. GAPPS is characterized by proximal gastric polyposis, increased risk of gastric adenocarcinoma, and no duodenal or colonic involvement in most individuals reported. [from GeneReviews]
Authors:
Timothy Yen  |  Peter P Stanich  |  Lisen Axell, et. al.   view full author information

Additional descriptions

From OMIM
Familial adenomatous polyposis-1 (FAP1) is an autosomal dominant disorder characterized by predisposition to cancer. Affected individuals usually develop hundreds to thousands of adenomatous polyps of the colon and rectum, a small proportion of which will progress to colorectal carcinoma if not surgically treated. Gardner syndrome is a variant of FAP in which desmoid tumors, osteomas, and other neoplasms occur together with multiple adenomas of the colon and rectum (Nishisho et al., 1991). Rustgi (2007) reviewed the genetics of hereditary colon cancer, including APC. Genetic Heterogeneity of Familial Adenomatous Polyposis See also autosomal recessive FAP2 (608456), caused by mutation in the MUTYH gene (604933) on chromosome 1p34; autosomal recessive FAP3 (616415), caused by mutation in the NTHL1 gene (602656) on chromosome 16p13; and autosomal recessive FAP4 (617100), caused by mutation in the MSH3 gene (600887) on chromosome 5q11.  http://www.omim.org/entry/175100
From MedlinePlus Genetics
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.

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.

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.  https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis

Clinical features

From HPO
Carcinoma
MedGen UID:
2867
Concept ID:
C0007097
Neoplastic Process
A malignant tumor arising from epithelial cells. Carcinomas that arise from glandular epithelium are called adenocarcinomas, those that arise from squamous epithelium are called squamous cell carcinomas, and those that arise from transitional epithelium are called transitional cell carcinomas (NCI Thesaurus).
Fibroma
MedGen UID:
42016
Concept ID:
C0016045
Neoplastic Process
Benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchyme tissue. The term "fibroblastic" or "fibromatous" is used to describe tumors of the fibrous connective tissue. When the term fibroma is used without modifier, it is usually considered benign, with the term fibrosarcoma reserved for malignant tumors.
Desmoid tumor
MedGen UID:
38187
Concept ID:
C0079218
Neoplastic Process
Benign, slow-growing tumors without any metastatic potential. Despite their benign nature, they can damage nearby structures causing organ dysfunction. Histologically they resemble low-grade fibrosarcomas, but they are very locally aggressive and tend to recur even after complete resection. There is a tendency for recurrence in the setting of prior surgery and the most common localisation of these tumors is intraabdominal from smooth muscle cells of the instestine.
Hepatoblastoma
MedGen UID:
61644
Concept ID:
C0206624
Neoplastic Process
A kind of neoplasm of the liver that originates from immature liver precursor cells and macroscopically is composed of tissue resembling fetal or mature liver cells or bile ducts.
Adrenocortical adenoma
MedGen UID:
61654
Concept ID:
C0206667
Neoplastic Process
Adrenocortical adenomas are benign tumors of the adrenal cortex.
Adrenal cortex carcinoma
MedGen UID:
104917
Concept ID:
C0206686
Neoplastic Process
A malignant neoplasm of the adrenal cortex that may produce hormones such as cortisol, aldosterone, estrogen, or testosterone.
Papillary thyroid carcinoma
MedGen UID:
66773
Concept ID:
C0238463
Neoplastic Process
The presence of a papillary adenocarcinoma of the thyroid gland.
Multiple lipomas
MedGen UID:
677074
Concept ID:
C0745730
Finding
The presence of multiple lipomas (a type of benign tissue made of fatty tissue).
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.
Odontoma
MedGen UID:
45181
Concept ID:
C0028882
Neoplastic Process
The presence of an odontoma.
Gastric polyposis
MedGen UID:
68629
Concept ID:
C0236048
Disease or Syndrome
A polyp that arises from the stomach. This category includes neoplastic polyps (intestinal-type adenomatous polyps, gastric-type adenomas, and fundic gland polyps), and non-neoplastic polyps (hyperplastic polyps and hamartomatous polyps).
Duodenal adenocarcinoma
MedGen UID:
82985
Concept ID:
C0278804
Neoplastic Process
A malignant epithelial tumor with a glandular organization that originates in the duodenum.
Duodenal polyposis
MedGen UID:
488924
Concept ID:
C0578477
Neoplastic Process
Presence of multiple polyps in the duodenum.
Adenomatous colonic polyposis
MedGen UID:
358118
Concept ID:
C1868071
Finding
Presence of multiple adenomatous polyps in the colon.
Small intestine carcinoid
MedGen UID:
356894
Concept ID:
C1868072
Finding
Astrocytoma
MedGen UID:
438
Concept ID:
C0004114
Neoplastic Process
Astrocytoma is a neoplasm of the central nervous system derived from astrocytes. Astrocytes are a type of glial cell, and thus astrocytoma is a subtype of glioma.
Medulloblastoma
MedGen UID:
7517
Concept ID:
C0025149
Neoplastic Process
Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (109400), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (see 276300). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (Crawford et al., 2007). Millard and De Braganca (2016) reviewed the histopathologic variants and molecular subgroups of medulloblastoma. Pretreatment prognosis of medulloblastoma has been refined by histopathologic subclassification into the following variants: large-cell medulloblastoma, anaplastic medulloblastoma, desmoplastic/nodular medulloblastoma, and medulloblastoma with extensive nodularity (MBEN). The latter 2 groups have been shown to have a significantly superior prognosis as compared to the large cell and anaplastic groups in young children. At the molecular level, medulloblastomas have been categorized into the following subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. Each subgroup is characterized by a unique set of genetics and gene expression as well as demographic and clinical features.
Keloid
MedGen UID:
7197
Concept ID:
C0022548
Acquired Abnormality
An irregularly shaped, elevated mark on the skin caused by deposits of excessive amounts of collagen during wound healing. It extends beyond the original boundaries of the wound and may enlarge progressively.
Osteoma
MedGen UID:
18220
Concept ID:
C0029440
Neoplastic Process
Osteomas are bony growths found most commonly on the skull and mandible; however, they may occur in any bone of the body. Osteomas do not usually cause clinical problems and do not become malignant.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Teeth, supernumerary
MedGen UID:
21210
Concept ID:
C0040457
Anatomical Abnormality
The presence of one or more teeth additional to the normal number.
Eruption failure
MedGen UID:
11856
Concept ID:
C0040458
Finding
A tooth which does not erupt within the teeth eruption timeline and after the loss of eruption potential.
Epidermoid cysts
MedGen UID:
41829
Concept ID:
C0014511
Anatomical Abnormality
Nontender, round and firm, but slightly compressible, intradermal or subcutaneous cyst measuring 0.5-5 cm in diameter. Epidermal cysts are intradermal or subcutaneous tumors, grow slowly and occur on the face, neck, back and scrotum. They usually appear at or around puberty, and as a rule an affected individual has one solitary or a few cysts.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Fibroadenoma of the breast
MedGen UID:
64231
Concept ID:
C0178421
Neoplastic Process
A benign biphasic tumor of the breast with epithelial and stromal components.
Congenital hypertrophy of retinal pigment epithelium
MedGen UID:
83290
Concept ID:
C0339555
Finding
Sharply demarcated, congenital hyperpigmentation of the retinal pigment epithelium.

Professional guidelines

PubMed

Rebuzzi F, Ulivi P, Tedaldi G
Int J Mol Sci 2023 Jan 21;24(3) doi: 10.3390/ijms24032137. PMID: 36768460Free PMC Article
Weiss JM, Gupta S, Burke CA, Axell L, Chen LM, Chung DC, Clayback KM, Dallas S, Felder S, Gbolahan O, Giardiello FM, Grady W, Hall MJ, Hampel H, Hodan R, Idos G, Kanth P, Katona B, Lamps L, Llor X, Lynch PM, Markowitz AJ, Pirzadeh-Miller S, Samadder NJ, Shibata D, Swanson BJ, Szymaniak BM, Wiesner GL, Wolf A, Yurgelun MB, Zakhour M, Darlow SD, Dwyer MA, Campbell M
J Natl Compr Canc Netw 2021 Oct 15;19(10):1122-1132. doi: 10.1164/jnccn.2021.0048. PMID: 34666312
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article

Curated

Aretz S, Vasen HF, Olschwang S
Eur J Hum Genet 2011 Jul;19(7) Epub 2011 Feb 2 doi: 10.1038/ejhg.2011.7. PMID: 21368914Free PMC Article

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer, 2024

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APC Pathogenic Variants (Familial Adenomatous Polyposis [FAP]), 2019

American College of Medical Genetics and Genomics Family History ACT Sheet, Colon Cancer (Asymptomatic), 2012

Suggested Reading

Recent clinical studies

Etiology

Carbone R, Rovedatti L, Lenti MV, Furlan D, Errichiello E, Gana S, Luinetti O, Arpa G, Alvisi C, De Grazia F, Valente EM, Sessa F, Paulli M, Vanoli A, Di Sabatino A
Dig Liver Dis 2021 Dec;53(12):1647-1654. Epub 2021 Apr 1 doi: 10.1016/j.dld.2021.03.011. PMID: 33814312
Silva-Velazco J, Hull TL, Stocchi L, Gorgun E
Dis Colon Rectum 2015 Mar;58(3):328-32. doi: 10.1097/DCR.0000000000000264. PMID: 25664711
Geisler D, Garrett T
Tech Coloproctol 2011 Dec;15(4):397-401. Epub 2011 Sep 2 doi: 10.1007/s10151-011-0756-7. PMID: 21887555
Aaltonen L, Johns L, Järvinen H, Mecklin JP, Houlston R
Clin Cancer Res 2007 Jan 1;13(1):356-61. doi: 10.1158/1078-0432.CCR-06-1256. PMID: 17200375

Diagnosis

Carbone R, Rovedatti L, Lenti MV, Furlan D, Errichiello E, Gana S, Luinetti O, Arpa G, Alvisi C, De Grazia F, Valente EM, Sessa F, Paulli M, Vanoli A, Di Sabatino A
Dig Liver Dis 2021 Dec;53(12):1647-1654. Epub 2021 Apr 1 doi: 10.1016/j.dld.2021.03.011. PMID: 33814312
Silva-Velazco J, Hull TL, Stocchi L, Gorgun E
Dis Colon Rectum 2015 Mar;58(3):328-32. doi: 10.1097/DCR.0000000000000264. PMID: 25664711
Geisler D, Garrett T
Tech Coloproctol 2011 Dec;15(4):397-401. Epub 2011 Sep 2 doi: 10.1007/s10151-011-0756-7. PMID: 21887555
Aaltonen L, Johns L, Järvinen H, Mecklin JP, Houlston R
Clin Cancer Res 2007 Jan 1;13(1):356-61. doi: 10.1158/1078-0432.CCR-06-1256. PMID: 17200375

Therapy

Silva-Velazco J, Hull TL, Stocchi L, Gorgun E
Dis Colon Rectum 2015 Mar;58(3):328-32. doi: 10.1097/DCR.0000000000000264. PMID: 25664711

Prognosis

Geisler D, Garrett T
Tech Coloproctol 2011 Dec;15(4):397-401. Epub 2011 Sep 2 doi: 10.1007/s10151-011-0756-7. PMID: 21887555

Clinical prediction guides

Scappaticci S, Fossati GS, Valenti L, Scabini M, Tateo S, Nastasi G, Spina MP, Capra E
Cancer Genet Cytogenet 1995 Jul 1;82(1):50-3. doi: 10.1016/0165-4608(94)00288-m. PMID: 7627934

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

    Curated

    • NCCN, 2024
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer, 2024
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, APC Pathogenic Variants (Familial Adenomatous Polyposis [FAP]), 2019
    • ACMG ACT, 2012
      American College of Medical Genetics and Genomics Family History ACT Sheet, Colon Cancer (Asymptomatic), 2012
    • EuroGenetest, 2011
      Clinical utility gene card for: familial adenomatous polyposis (FAP) and attenuated FAP (AFAP).

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