Familial adenomatous polyposis (FAP) is characterized by the development of many 
tens to thousands of adenomas in the rectum and colon during the second decade 
of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in 
both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In 
the European Union, prevalence has been estimated at 1/11,300-37,600. Most 
patients are asymptomatic for years until the adenomas are large and numerous, 
and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers 
start to develop a decade after the appearance of the polyps. Nonspecific 
symptoms may include constipation or diarrhea, abdominal pain, palpable 
abdominal masses and weight loss. FAP may present with some extraintestinal 
manifestations such as osteomas, dental abnormalities (unerupted teeth, 
congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts 
and odontomas), congenital hypertrophy of the retinal pigment epithelium 
(CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts 
and central nervous system). A less aggressive variant of FAP, attenuated FAP 
(AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 
100), later age of adenoma appearance and a lower cancer risk. Some lesions 
(skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, 
shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic 
FAP is inherited in an autosomal dominant manner and results from a germline 
mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a 
family history of colorectal polyps and cancer. In a subset of individuals, a 
MUTYH mutation causes a recessively inherited polyposis condition, 
MUTYH-associated polyposis (MAP), which is characterized by a slightly increased 
risk of developing CRC and polyps/adenomas in both the upper and lower 
gastrointestinal tract. Diagnosis is based on a suggestive family history, 
clinical findings, and large bowel endoscopy or full colonoscopy. Whenever 
possible, the clinical diagnosis should be confirmed by genetic testing. When 
the APC mutation in the family has been identified, genetic testing of all 
first-degree relatives should be performed. Presymptomatic and prenatal 
(amniocentesis and chorionic villous sampling), and even preimplantation genetic 
testing is possible. Referral to a geneticist or genetic counselor is mandatory. 
Differential diagnoses include other disorders causing multiple polyps (such as 
Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, 
hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and 
maintaining a good quality of life are the main goals of management and regular 
and systematic follow-up and supportive care should be offered to all patients. 
By the late teens or early twenties, colorectal cancer prophylactic surgery is 
advocated. The recommended alternatives are total proctocolectomy and ileoanal 
pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the 
two main causes of mortality after total colectomy, they need to be identified 
early and treated. Upper endoscopy is necessary for surveillance to reduce the 
risk of ampullary and duodenal cancer. Patients with progressive tumors and 
unresectable disease may respond or stabilize with a combination of cytotoxic 
chemotherapy and surgery (when possible to perform). Adjunctive therapy with 
celecoxib has been approved by the US Food and Drug Administration and the 
European Medicines Agency in patients with FAP. Individuals with FAP carry a 
100% risk of CRC; however, this risk is reduced significantly when patients 
enter a screening-treatment program.