Familial adenomatous polyposis

Abstract

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. ...

Adenomatous Polyposis in a Young Jamaican Male of African Descent

“…His family requested perfluorocarbon transfusion over packed red blood cells. The former was not population at large, and only a few case reports describe the development of high grade dysplasia or gastric adenocarcinoma associated with diffuse fundic gland polyposis in patients with FAP (10). The histology of the fundic polyp for the index case revealed low grade dysplasia, which puts him at low risk for upper gastrointestinal malignancy.…”

Classification of Colorectal Cancer Based on Molecular Features

“…CRC is divided into three categories: hereditary, nonhereditary and familial [2,3]. Approximately 15% of CRC cases are considered as a hereditary form which most common contains: Familial adenomatous polyposis (FAP) and hereditary non polyposis colorectal cancer (HNPCC) and MYHAssociated polyposis (MAP) [4,5].…”

The growing complexity of the intestinal polyposis syndromes

“…Furthermore, adenomas are frequently flat ("hereditary flat adenoma syndrome") and often localized in the proximal colon ("rectal sparing"). AFAP patients are at high risk of CRC (Table I), which is diagnosed on average at 56 years [Half et al, 2009], that is 10 years earlier than sporadic CRC and 15-20 years later than in classical FAP. Extra-colonic manifestations may or not be present, but upper GI lesions are generally present.…”