Genetics

The Genetics of FAP: How It Happens and How It Is Inherited

At a Glance

Familial Adenomatous Polyposis (FAP) is an inherited condition caused by a mutation in the APC gene, which normally stops tumors from forming. Inheriting just one mutated gene causes hundreds of colon polyps to grow, making genetic testing essential for patients and their relatives.

To understand Familial Adenomatous Polyposis (FAP), it helps to think of your DNA as a set of instructions for building and maintaining your body. One specific instruction, the APC gene, acts as a “braking system” for cell growth. When this gene is mutated, the brakes fail, leading to the uncontrolled growth of polyps.

The Role of the APC Gene

The APC gene is a tumor suppressor gene ^[1]. Its normal job is to produce a protein that controls how often cells divide and how they stick to each other. It does this primarily by managing another protein called β-catenin ^[2].

How it normally works: The APC protein helps destroy excess β-catenin so it doesn’t build up ^[1]^[2].
What happens in FAP: When the APC gene is mutated, it can’t break down β-catenin properly. The β-catenin levels rise and move into the cell’s “control center” (the nucleus), where it signals the cell to grow and divide constantly ^[1]^[3]. This results in the hundreds or thousands of polyps seen in FAP.

How FAP is Passed Down

FAP is typically inherited in an autosomal dominant pattern ^[4]. This means:

One copy is enough: You only need to inherit one mutated copy of the APC gene from one parent to have the condition ^[4].
50/50 Chance: An affected parent has a 50% chance of passing the mutation to each child ^[4].
De Novo Mutations: While many inherit FAP, it can also happen for the first time in an individual due to a de novo (new) mutation, even if neither parent has the condition ^[5]^[6].

The Two Faces of FAP: Classic vs. Attenuated

Not all FAP looks the same. The severity often depends on where exactly the mutation is located on the APC gene ^[7]^[8].

Feature	Classic FAP	Attenuated FAP (AFAP)
Polyp Count	Hundreds to thousands ^[9]	Usually fewer than 100 ^[10]
Onset Age	Often in the teens ^[4]	Older age of onset for polyps ^[10]
Cancer Risk	Nearly 100% if untreated ^[4]	High risk, but often later in life ^[11]^[10]

A Different Path: MUTYH-Associated Polyposis (MAP)

Sometimes, a patient has dozens of polyps, but their APC gene is normal. They may instead have MUTYH-Associated Polyposis (MAP) ^[12].

While MAP looks very similar to Attenuated FAP, it is a different genetic situation:

Autosomal Recessive Inheritance: Unlike FAP, MAP is recessive ^[12]. You must inherit two mutated copies—one from each parent—to have the condition.
Family History: In FAP families, you often see the condition in every generation. In MAP, you may be the only person in your family with it, or only your siblings may be affected ^[12].
Clinical Presentation: MAP often presents with a lower number of polyps than classic FAP and carries a high risk of colorectal cancer ^[13]^[14].

The Importance of Genetic Testing

Because FAP, AFAP, and MAP can look so similar on a colonoscopy, germline genetic testing (testing your DNA) is the only way to know for sure which condition you have ^[13]^[12]. This diagnosis is vital because it determines how often you need screenings and helps your family members know if they are also at risk.

Common questions in this guide

How is Familial Adenomatous Polyposis (FAP) inherited?

FAP is typically inherited in an autosomal dominant pattern. This means you only need to inherit one mutated copy of the APC gene from one parent to develop the condition, giving each child of an affected parent a 50% chance of inheriting it.

What does the APC gene do in the body?

The APC gene acts as a tumor suppressor by controlling how often cells divide. When the APC gene is mutated, it can no longer regulate cell growth, leading to the rapid formation of precancerous polyps in the colon.

What is the difference between Classic FAP and Attenuated FAP?

Classic FAP usually causes hundreds to thousands of polyps beginning in the teen years. Attenuated FAP (AFAP) is a milder form that typically causes fewer than 100 polyps and develops later in life, though both carry a high risk for colon cancer.

What is MUTYH-Associated Polyposis (MAP) and how does it differ from FAP?

MAP is a genetic condition that looks similar to FAP but is caused by mutations in the MUTYH gene rather than the APC gene. Unlike FAP, MAP is a recessive condition, meaning you must inherit a mutated gene from both parents to have it.

Why is genetic testing important if I have multiple colon polyps?

Genetic testing is the only definitive way to distinguish between Classic FAP, Attenuated FAP, and MAP, which can look identical during a colonoscopy. Identifying your specific gene mutation helps determine your cancer risk and guides screening plans for both you and your family.

Curated prompts to bring to your next appointment.

1.What is the exact name and location of the mutation found in my genetic testing?
2.Does my mutation suggest a 'Classic' or 'Attenuated' form of FAP?
3.Is my diagnosis FAP (APC gene) or MAP (MUTYH gene), and how does that change the risk for my children or siblings?
4.If no mutation was found in my blood work, should we consider testing my polyp tissue for 'mosaic' FAP?
5.Does the location of my mutation put me at a higher risk for specific symptoms outside of the colon?

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References (14)

1
The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling.
Kunttas-Tatli E, Von Kleeck RA, Greaves BD, et al.
Molecular biology of the cell 2015; (26(24)):4503-18 doi:10.1091/mbc.E15-07-0515.
PMID: 26446838
2
Cell Biology of Canonical Wnt Signaling.
Albrecht LV, Tejeda-Muñoz N, De Robertis EM
Annual review of cell and developmental biology 2021; (37()):369-389 doi:10.1146/annurev-cellbio-120319-023657.
PMID: 34196570
3
A Case of Sporadic Multiple Colonic Polyps in a Young Woman.
Sin SH, Yoon JH, Kim SW, et al.
Current oncology (Toronto, Ont.) 2023; (30(2)):1293-1299 doi:10.3390/curroncol30020100.
PMID: 36826061
4
Targeted next-generation sequencing approach for molecular genetic diagnosis of hereditary colorectal cancer: Identification of a novel single nucleotide germline insertion in adenomatous polyposis coli gene causes familial adenomatous polyposis.
Wang D, Liang S, Zhang X, et al.
Molecular genetics & genomic medicine 2019; (7(1)):e00505 doi:10.1002/mgg3.505.
PMID: 30523670
5
Two cases of genetic testing for familial adenomatous polyposis without a family history.
Makutani Y, Iwamoto M, Daito K, et al.
International cancer conference journal 2025; (14(4)):387-395 doi:10.1007/s13691-025-00782-x.
PMID: 41395568
6
Familial adenomatous polyposis: a case report.
Kindie EA, Beyera TD, Teferi ET, et al.
Journal of medical case reports 2024; (18(1)):415 doi:10.1186/s13256-024-04724-8.
PMID: 39244621
7
Aggressive mutation in a familial adenomatous polyposis syndrome family: when phenotype guides clinical surveillance.
Neffa F, Garcia L, Della Valle A, et al.
Journal of gastrointestinal oncology 2018; (9(3)):553-559 doi:10.21037/jgo.2017.10.06.
PMID: 29998021
8
Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells.
Kajino-Sakamoto R, Fujishita T, Taketo MM, Aoki M
Oncogene 2021; (40(2)):408-420 doi:10.1038/s41388-020-01541-3.
PMID: 33177648
9
Familial Adenomatous Polyposis.
Waller A, Findeis S, Lee MJ
Journal of pediatric genetics 2016; (5(2)):78-83 doi:10.1055/s-0036-1579760.
PMID: 27617147
10
Attenuated adenomatous polyposis of the large bowel: Present and future.
Roncucci L, Pedroni M, Mariani F
World journal of gastroenterology 2017; (23(23)):4135-4139 doi:10.3748/wjg.v23.i23.4135.
PMID: 28694653
11
Cancer Incidence and Mortality in Familial Adenomatous Polyposis Syndrome.
Feldman D, Rodgers-Fouche LH, Ukaegbu C, et al.
Diseases of the colon and rectum 2025; (68(5)):531-543 doi:10.1097/DCR.0000000000003645.
PMID: 39932215
12
c.1227_1228dupGG (p.Glu410Glyfs), a frequent variant in Tunisian patients with MUTYH associated polyposis.
Kdissa A, Brusgaard K, Ksiaa M, et al.
Cancer genetics 2020; (240()):45-53 doi:10.1016/j.cancergen.2019.10.007.
PMID: 31739127
13
Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.
Zaffaroni G, Mannucci A, Koskenvuo L, et al.
The British journal of surgery 2024; (111(5)) doi:10.1093/bjs/znae070.
PMID: 38722804
14
NTHL1 and MUTYH polyposis syndromes: two sides of the same coin?
Weren RD, Ligtenberg MJ, Geurts van Kessel A, et al.
The Journal of pathology 2018; (244(2)):135-142 doi:10.1002/path.5002.
PMID: 29105096

This page provides educational information about the genetics and inheritance of FAP. Always consult a genetic counselor or your physician to discuss your specific genetic test results and family risks.

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