Familial Adenomatous Polyposis

Familial Adenomatous Polyposis

Familial adenomatous polyposis is a genetic disorder that causes cancer of the large intestine (colon) and rectum. People with this condition develop more than 100 non-cancerous growths (polyps) in their colon.

Familial adenomatous polyposis (FAP) is a highly penetrant, autosomal-dominant condition characterized by hundreds of colorectal adenomatous polyps that inevitably progress to cancer. 

FAP is an autosomal dominant syndrome characterized by innumerable bowel polyps and other findings.

If this condition is not treated, the polyps will turn into colon cancer. This condition also increases the risk of other types of cancer.

Spontaneous genetic mutations occasionally result in this syndrome.

With this condition, people usually develop polyps in the colon when they are a teenager. To prevent cancer, surgery is usually done to remove the colon.

Gardner syndrome is a subset of FAP, with prominent extraintestinal manifestations including dental abnormalities, soft tissue lesions, desmoid tumors, and osteomas.

Epidemiology & Demographics

  • •Familial Adenomatous Polyposis occurs in approximately 1 in 10,000 births worldwide.
  • •Familial Adenomatous Polyposis accounts for <1% of all colorectal cancers.
  • •Individuals develop hundreds to thousands of adenomatous colorectal polyps.
  • •Polyps usually present in adolescence.
  • •100% lifetime risk for colorectal cancer; most diagnosed by 40 yr of age.
  • •Gastric, duodenal, periampullary, and small bowel polyps occur but have lower malignant potential.
  • •Increased risk for other tumors: Desmoid (15%), duodenal/periampullary (7%), thyroid (2%), brain (1%), childhood hepatoblastoma (1%), nasopharyngeal angiofibroma (benign), pancreatic (2%), adrenal adenoma (10%), and gastric (1%).

What is the most common location of the polyps in patients with FAP?

Colon > stomach > duodenum > small bowel.

What are the Symptoms?

Symptoms of Familial Adenomatous Polyposis include:

  • A large number of polyps in the colon.
  • Growths in other places besides the colon.
  • Blood in your stool (feces).
  • Stomach pain.
  • Cramps.
  • Unexplained weight loss.
  • Problems with your teeth.
  • Harmless bone tumors (osteomas).
  • Changes in bowel movements.
  • Diarrhea or vomiting.

What are the Physical Findings & Clinical Features?

Phenotypic variability is seen in individuals and families with the same mutation. Extra-intestinal manifestations may precede intestinal disease. These findings are reported in at least 20% of individuals with Familial Adenomatous Polyposis.

  • •Congenital hypertrophy of the retinal pigment epithelium (CHRPE): Benign fundus lesions, usually present at birth
  • •Dental abnormalities: Supernumerary or unerupted teeth
  • •Soft tissue lesions: Epidermal or sebaceous cysts, fibromas, lipomas, desmoid tumors (benign, locally invasive, aggressive connective tissue tumor)
  • •Osteomas (benign bone growths): Skull, mandible, long bone
  • •Anemia, occult blood in stool, bowel obstruction, weight loss

What is the risk of developing CRC in patients with FAP syndrome? 

FAP syndrome presents as more than 100 adenomas throughout the colon and is caused by mutations in the APC gene.

The risk of developing CRC in patients with FAP is almost 100% by age 40 to 50 years.

Total colectomy is indicated in patients with FAP who develop multiple, diffuse adenomas in the colon.

What increases the risk of this condition?

You are more likely to develop Familial Adenomatous Polyposis if:

  • One of your parents or siblings has familial adenomatous polyposis.
  • You have a family history of familial adenomatous polyposis.
  • You have Crohn disease.

What causes Familial Adenomatous Polyposis?

Familial Adenomatous Polyposis is caused by abnormal changes in genes (gene mutations) that are passed down through families (inherited).

  • •FAP is caused by mutations of the tumor suppressor gene adenomatous polyposis coli (APC) on chromosome 5q21 to q22; more than 1000 disease-causing mutations identified. The site of the mutation often correlates with the extraintestinal findings.
  • •De novo mutations are responsible for approximately 20% of FAP cases. These may be due to germline mutations or somatic cell mosaicism, which is seen when a new mutation occurs in the APC gene post-fertilization and is present in only a subset of cell types or tissues.

The below table summarizes the genetics of colonic polyposis.

Genetics of Colonic Polyposis

From Niederhuber JE: Abeloff’s clinical oncology, ed 6, Philadelphia, 2020, Elsevier.

Syndrome (Abbreviation, Synonym)Gene(s)Molecular PhenotypeNoncolonic Organs Affected
Sporadic adenomatous polypUnknownChromosomal instability (aneuploidy)None known
Familial adenomatous polyposis (FAP)APCChromosomal instability (aneuploidy)Duodenum, stomach, pancreas, thyroid, liver, central nervous system
Attenuated familial adenomatous polyposis (AFAP)APCChromosomal instability (aneuploidy)Duodenum, thyroid, liver, central nervous system
Hereditary nonpolyposis colon cancer (HNPCC, Lynch syndrome)hMLH1, hMSH2, hMSH6, hPMS2MSIEndometrium, stomach, ovary, biliary and urinary tracts, small bowel, central nervous system
MUTYH-linked adenomatous polyposis (MAP)MUTYHChromosomal instability (aneuploidy)Duodenum
Peutz-Jeghers syndrome (PJS)STK1 (70%)UnknownBreast, pancreas, stomach, ovary, lung, small bowel, uterus, testis
Juvenile polyposis syndromeSMAD4, BMPR1AUnknownBlood vessels (hereditary hemorrhagic telangiectasia)
Hyperplastic polyposisSMAD4, BMPR1A (40%), PTENUnknownStomach, pancreas, small bowel

MSI, Microsatellite instability.

What are the major variants of Familial Adenomatous Polyposis?

Attenuated Familial Adenomatous Polyposis, characterized by <100 adenomatous polyps in the colon and older age of diagnosis; familial polyposis coli, characterized by multiple enteric polyps; and Gardner’s syndrome, characterized by a combination of enteric polyps, osteomas, soft tissue tumors (e.g., desmoid tumors, ampullary/duodenal tumors, and papillary thyroid cancers), and dental abnormalities.

How is Familial adenomatous polyposis diagnosed?

This condition is diagnosed based on:

  • Imaging tests to check the colon for polyps.
  • A genetic test to determine if you are at risk for this disease.

In individuals with a family history, more than 100 adenomatous colorectal polyps, CHRPE lesions, or positive genetic testing confirms diagnosis.

In those without a family history, more than 100 adenomatous colorectal polyps suggest the diagnosis, and genetic testing confirms it.

The diagnosis should be considered in individuals with ≥10 adenomatous colorectal polyps or fewer polyps in the presence of extraintestinal findings.

When should endoscopic screening begin in patients with Familial Adenomatous Polyposis

Genetic testing should be offered to all patients at risk for FAP and to family members prior to endoscopic screening. Beginning at age 10 to 12, individuals at risk for FAP should undergo annual flexible sigmoidoscopy until 40 years of age and then every 3 to 5 years thereafter.

Family members are assumed not to be affected if their genetic test is negative and the index case is positive but can be offered sigmoidoscopy every 7 to 10 years to account for any potential errors in the test.

Differential Diagnosis

  • •Turcot syndrome
  • •Attenuated FAP (also APC gene mutation, but presents with fewer polyps [<100], at a later age, and has lower cancer risk than FAP [∼80% lifetime risk])
  • •MUTYH-associated polyposis
  • •Peutz-Jeghers syndrome
  • •Juvenile polyposis syndrome
  • •Cowden disease
  • Lynch syndrome
  • •Hereditary mixed polyposis syndrome
  • •Polymerase proofreading-associated polyposis
  • •Hyperplastic polyposis

The below table compares various adenomatous polyposis syndromes.

Adenomatous Polyposis Syndromes

From Feldman M et al (eds): Sleisenger and Fordtran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Saunders.

SyndromeGene MutationPolypsExtraintestinal Abnormalities
Classic FAPAPC (usually truncated protein)Colonic adenomas (thousands)
Duodenal, periampullary adenomas
Gastric fundic gland polyps
Jejunal and ileal adenomas
Ileal lymphoid polyps
Mandibular osteomas
Dental abnormalities
Gardner variant of FAPAPCSame as FAPOsteomas (mandible, skull, long bones)
Desmoid tumors
Epidermoid and sebaceous cysts
Fibromas, lipomas
Thyroid, adrenal tumors
Turcot variant of FAPAPC DNA MMR Colonic adenomas (sometimes fewer than in classic FAP)Medulloblastoma
Glioblastoma multiforme
Attenuated FAPAPC 5′ and 3′ regionsColonic adenomas (<100; proximal colon)
Duodenal, periampullary adenomas
Gastric fundic gland polyps
Mandibular osteomas (rare)
Familial tooth agenesisAxin2 (APC pathway)Colonic adenomas
Hyperplastic polyps
Agenesis of teeth
Bloom syndromeBLMColonic adenomasSmall stature
Facial erythema/telangiectasia
Male sterility
Adenocarcinomas, leukemia, lymphoma
MUTYH polyposisMUTYH (MYH)Colonic adenomas (5-100)CHRPE
Duodenal polyposis
Gastric cancer

APC, Adenomatous polyposis coli; CHRPE, congenital hypertrophy of the retinal pigment epithelium; DNA, deoxyribonucleic acid; FAP, familial adenomatous polyposis; MMR, mismatch repair.

∗ May be more appropriately classified under hereditary nonpolyposis colon cancer.

What is the risk of colorectal cancer among patients with untreated FAP?

Virtually 100% by approximately 35 years of age.


History, physical examination, laboratory tests, imaging studies

Diagnostic Screening Options

Genetic Testing

note: Genetic counseling should be performed, and written informed consent obtained before testing. Refer to a specialized center for counseling and evaluation.

  • •Should be offered to first-degree relatives of affected individuals (with an identified mutation) at age 10 to 12 yr and clinically suspected individuals.
  • •Able to identify a mutation in approximately 80% of families. To ensure that the family has a detectable mutation, test an affected family member first.
  • •If positive in the affected individual, the test can differentiate with 100% accuracy affected and unaffected family members. If negative in the affected individual, screening family members will not be useful in determining disease status.
  • •If no known family history exists, screening the clinically suspected individual is reasonable. A positive test rules in FAP but a negative test does not rule it out.
  • •Numerous testing techniques available; may require multiple tests to identify the mutation.


  • •Individuals with a positive genetic test: Annual flexible sigmoidoscopy or colonoscopy beginning at 10 to 12 yr of age.
  • •Untested at-risk family members or individuals from families with an unidentified APC mutation: Annual flexible sigmoidoscopy or colonoscopy beginning at 10 to 12 yr of age. Screening frequency can decrease at 24 yr of age if no polyps detected.
  • •Once adenomatous polyps are detected, patients should undergo colonoscopy and evaluation for colectomy.
  • •Negative genetic test in patients from families with an identified mutation: Average risk screening.


Lesions occur in up to 80% of families and are a reliable indicator of affected status in these families.

How is Familial Adenomatous Polyposis treated?

This condition is treated with surgery to remove the colon (colectomy). Regular screening with a procedure to view the entire colon (colonoscopy) may be needed prior to surgery. People with this condition may need regular colonoscopies starting as young as age 10.

  • •Prophylactic colectomy or proctocolectomy: Timing determined by polyp number, size, and degree of dysplasia. Postsurgical endoscopic surveillance annually.
  • •Additional screening:
    • 1.Annual physical examination: History, examination (including thyroid), and blood tests
    • 2.Upper endoscopy to screen for gastric/duodenal polyps (include visualization of duodenal papilla): Baseline at age 25 yr (earlier if colon polyps detected) and repeated every 3 mo to 4 yr based on findings
    • 3.Annual thyroid ultrasound: Begin in teenage yrs
    • 4.Other possible cancer sites imaged if symptoms occur or if these cancers have occurred in relatives
  • •Treat soft tissue lesions and osteomas for symptoms or cosmetic concerns. Treat desmoid tumors if they pose a risk to adjacent structures.

Is surgery mandatory?

Prophylactic total colectomy at about 20 years of age.


  • •100% chance of colorectal cancer in untreated individuals. Many other neoplasms occur at higher rates.
  • •Metastatic colorectal cancer is the leading cause of death (58%), followed by desmoid tumors (11%), and duodenal/periampullary adenocarcinoma (8%).


  • •Patients should be managed at centers with expertise in FAP, including a gastroenterologist, medical geneticist, and surgeon.
  • •Genetic counselors can be found at www.nsgc.org.
  • •Genetic clinics and laboratories can be found at www.ncbi.nlm.nih.gov/gtr.

 Pearls & Considerations

  • •Management should be individualized based on genotype, phenotype, and individual preferences.
  • •Sulindac (NSAID) and celecoxib (COX-2 inhibitor) can cause duodenal and colorectal polyp regression in individuals with Familial Adenomatous Polyposis. Preliminary studies with other agents also show polyp regression. Their ability to reduce cancer risk remains unknown; they do not replace colon resection for cancer prevention.
  • •Desmoid tumors usually present in the 30s, frequently occur in the abdomen, and are difficult to treat with high rates of recurrence. Growth and recurrence are stimulated by surgery.
  • •Screen children of affected parents (from infancy to age 7 yr) biannually with alpha-fetoprotein level and liver ultrasound to rule out hepatoblastoma.
  • •Preimplantation and prenatal genetic testing is available.
  • •Attenuated FAP: Screening colonoscopy every 1 to 2 yr starting at 20 yr of age.

Follow these instructions at home:

  • Keep all follow-up visits as told by your health care provider. This is important.
  • Take over-the-counter and prescription medicines only as told by your health care provider.
  • Consider joining a support group with others who have this condition.
  • Ask about the importance of genetic testing for other family members.
  • Monitor your condition and report any changes to your health care provider.

Contact a health care provider if:

  • You have new symptoms that do not go away.
  • You have stomach pain that does not go away.
  • You are losing weight and you are not sure why.

Get help right away if:

  • You have blood in your stool.
  • Your symptoms get worse.


  • Familial adenomatous polyposis is a genetic disorder that causes cancer of the large intestine (colon) and rectum. People with this condition develop more than 100 non-cancerous growths (polyps) in their colon.
  • If this condition is not treated, the polyps will turn into colon cancer. This condition also increases the risk of other types of cancer.
  • A genetic test is done to determine if you are at risk for this disease.
  • This condition is treated with surgery to remove the colon (colectomy).

Seek Additional Information

  • Chenbhanich J., et al.: Prevalence of thyroid diseases in familial adenomatous polyposis: a systematic review and meta-analysis. Fam Cancer 2019; 18: pp. 53.
  • Herzig D., et al.: The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of inherited polyposis syndromes. Dis Colon Rectum 2017; 60: pp. 881.
  • Kanth P., et al.: Hereditary colorectal polyposis and cancer syndromes: a primer on diagnosis and management. Am J Gastroenterol 2017; 112: pp. 1509.
  • Leiden Open Variation Database: APC (adenomatous polyposis coli). 
  • Samadder N.J., et al.: Association of sulindac and erlotinib vs placebo with colorectal neoplasia in familial adenomatous polyposis: secondary analysis of a randomized clinical trial. JAMA Oncol 2018; 4: pp. 671.
  • Syngal S., et al.: ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 2015; 110: pp. 223.

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