Familial Adenomatous Polyposis

Summary: Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome caused by carrying an APC gene pathogenic variant (mutation).

By JAX Clinical Education | July 2026

Clinical Features

Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome and includes a milder, attenuated form (AFAP) of the disease. Individuals with FAP develop hundreds to thousands of adenomatous polyps in their colon, sometimes beginning in childhood. Without surgical intervention, they have nearly a 100% risk of developing colorectal cancer. Untreated, the mean age of colon cancer diagnosis is 39. Individuals who have AFAP generally develop 100 or fewer polyps in their lifetime. They have a lower risk of colorectal cancer (approximately 70%) than individuals who have classic FAP.

Individuals with FAP/AFAP also have an increased risk for other cancers, including upper gastrointestinal tract tumors, pancreatic, thyroid, central nervous system, and liver (hepatoblastoma in children under age 5) cancer. Rare individuals with specific APC genetic variants develop massive polyposis of the stomach and have an increased risk of gastric adenocarcinoma (GAPPS). Non-cancer features of FAP/AFAP include congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, epidermoid cysts, osteomas, dental abnormalities, gastric fundic gland polyps, and gastric and duodenal adenomas.

Cancer risks through age 80 associated with FAP

Cancer Type	FAP	General Population
Colorectal	Approaches 100%	4.0%
Duodenum	Up to 10%	NE
Gastric	Up to 7.1%	0.8%
Thyroid, papillary	Up to 12%	1.2%
Central nervous system	1%	NE
Hepatoblastoma	Up to 2.5%	<1%

NE: Not established

Adapted from NCCN v.1.2026

Prevalence of FAP

FAP is a rare condition affecting approximately 1 in 6,800 to 31,000 individuals. FAP accounts for less than 1% of colorectal cancer cases.

Diagnosis

Identification of a pathogenic variant (mutation) in the APC gene is sufficient for the diagnosis of FAP/AFAP.

Clinical Criteria

A diagnosis of FAP is now established by molecular genetic testing. In the absence of genetic testing, a clinical diagnosis can be made if an individual has early onset of 100 or more adenomatous colon polyps.

There are no clinical diagnostic criteria for AFAP. Generally, a clinical diagnosis is suspected when an individual has between 10 and 99 adenomatous colon polyps, or more than 100 polyps diagnosed at an older age than that expected for FAP (age 35–40 or older).

Genetics & Inheritance

FAP/AFAP is an autosomal dominant condition caused by a pathogenic variant in APC. First-degree relatives of an APC carrier have a 50% chance of also carrying the variant. Men and women are equally likely to inherit, and pass on, a pathogenic variant. Seventy percent of cases are familial or inherited and 20-25% of cases are de novo, or sporadic, pathogenic mutations.

Clinical Testing

Germline molecular testing includes sequencing and deletion/duplication analysis of APC, often analyzed as part of a larger multigene hereditary cancer panel.

Genetic Testing Criteria

Criteria have been developed to identify individuals who would most benefit from genetic testing, based on red flags in the personal and family cancer history. Generally this includes:

Personal history of ≥20 cumulative adenomas
Known pathogenic/likely pathogenic variant in family
Multifocal/bilateral congenital hypertrophy of retinal pigment epithelium (CHRPE)
Other considerations, such as 10-19 cumulative adenomas, desmoid tumor, hepatoblastoma, certain thyroid cancers, unilateral CHRPE, serrated polyposis syndrome

See the NCCN guidelines below for specific testing criteria.

Management

Management of classic FAP and AFAP may differ significantly. Management by physicians or centers with expertise in FAP and AFAP is recommended, and recommendations should be individualized based on clinical presentation and specific APC variant, as well as other personal considerations. Management usually includes early screening and colectomy or proctocolectomy after the onset of polyposis. Screening should also include evaluation for extra-intestinal manifestations. For children under 5 years of age, screening may also includes liver palpation, abdominal ultrasound, and measurement of AFP. Published guidelines with age-specific management recommendations are available (see below).

While almost all APC pathogenic variants result in AFAP/FAP, there is a common APC variant, I1307K, which only confers a moderate lifetime risk of colorectal cancer. This variant is seen in 6 - 10% of the Ashkenazi Jewish population. Colonoscopy screening in these individuals should begin at age 40, or 10 years prior to any colorectal cancer diagnosis in a first-degree relative, and repeated every 5 years if negative.

Other Genes that Contribute to Polyposis

There are other hereditary cancer syndromes that increase the risk for polyps and colorectal cancer, including MUYTH-associated polyposis (MAP), Juvenile Polyposis syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. The presentation of these syndromes in a family may overlap with that of FAP/AFAP, but can sometimes be distinguished based on characteristic features, such as physical exam findings and polyp pathology. In addition, a number of common genetic susceptibility variants are thought to increase polyp and colorectal cancer risk beyondAPC. There are likely other genes that contribute to polyp development which have not yet been identified. See GeneReviews for more information about the genetic differential diagnosis for FAP.