Familial multiple polyposis syndrome, or familial adenomatous polyposis (FAP), is a genetic disorder that predisposes patients to colorectal cancer. It is a germline autosomal-dominant inherited mutation in the APC gene on chromosome 5. APC is a tumor suppressor gene. FAP has an incidence at birth of approximately 1/10 000 in the general population and accounts for 1% of colorectal cancer.

Patients will often have polyps starting in adolescence or young adulthood and can have hundreds to thousands of colonic polyps by mid-adulthood. Most patients present between the second and fourth decades of life, generally with gastrointestinal tract bleeding, abdominal pain, or diarrhea. The average age of FAP patients when colorectal cancer is diagnosed is 40 years old, and the incidence of colorectal cancer approaches 100% with age. Attenuated FAP is a phenotype of FAP with a slightly smaller risk of colorectal cancer that presents later in life.

Patients with FAP are at increased risk for other malignancies, in particular tumors of the desmoid, pancreas, stomach, thyroid, small intestine, hepatoblastoma, and osteomas.

Another APC-related polyposis condition with a similar phenotype is MUTYH-associated polyposis (MAP), an autosomal-recessive mutation of the MUTYH gene associated with an 80% lifetime risk of colorectal cancer. Genetic testing for MAP should be pursued in patients with more than 10 adenomatous polyps, a known family history of MAP, or serrated polyposis syndrome. MAP is also associated with an increased risk of duodenal cancers, as well as higher rates of bladder, ovarian, breast, and skin cancer.

Turcot syndrome is characterized by brain tumors and associated familial colorectal cancer syndromes, and may be associated with FAP or Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Related topic: Gardner syndrome