History and exam

Key diagnostic factors

common

family history of FAP/attenuated FAP

Approximately 70% of patients have a family history of familial adenomatous polyposis (FAP); however, up to 30% of FAP probands have no family history of polyposis or colorectal cancer; these cases may be explained by somatic mosaicism in the adenomatous polyposis coli gene.[3][4][5]​​

teenager

Familial adenomatous polyposis (FAP): median age of onset for polyps in FAP is 15 years.[8]

onset of colorectal cancer in middle age

Familial adenomatous polyposis (FAP): colorectal cancer onset nearly 100% by 40 years of age without treatment.[1][6]

Attenuated FAP: average age of colorectal cancer onset is 55 years without treatment.[11]

bilateral pigmentation of the retina

Unilateral pigmentation is common in the general population.

More than 4 unilateral or bilateral hypertrophies of the retinal pigment epithelium can be an indicator of familial adenomatous polyposis regardless of family history.[32][33]​​

Other diagnostic factors

uncommon

constipation/diarrhea

Polyps may lead to symptomatic changes in bowel frequency.

hematochezia

Polyps may lead to symptomatic changes in bowel habits.

extraintestinal features of familial adenomatous polyposis (FAP)

Extraintestinal manifestations of FAP may be evident and prompt genetic testing.[24][28]​ These include skin cysts, lipomas and fibromas, supernumerary teeth, thyroid nodules, osteomas, desmoid tumors, adrenal adenomas, and congenital hypertrophy of the retinal pigment epithelium.[10]

Risk factors

strong

germline adenomatous polyposis coli (APC) gene mutation

Both familial adenomatous polyposis (FAP) and attenuated FAP are mainly caused by germline mutations in the APC gene, located on chromosome 5q21, which encodes a tumor suppressor.[14]​ Mutations throughout the gene are associated with FAP, while attenuated FAP more commonly occurs when the mutation is located in the 5' or 3' region of the gene.[15]​

family history of familial adenomatous polyposis (FAP) or attenuated FAP

Around two-thirds of patients have a family history of FAP/attenuated FAP, and this is the most common reason for a patient to seek evaluation.[2]​ However, because of the high rate of spontaneous adenomatous polyposis coli mutations, about one third of patients will not have a family history, and so its absence should not preclude consideration of the diagnosis.[3]​

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