Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to the development of hundreds to thousands of adenomatous polyps throughout the colon and rectum (MIM 175100). Left untreated, it is almost 100% certain that at least one of these polyps will become malignant, usually by the time the patient is 40 yr of age (1 ). Affected patients may also develop a range of extracolonic manifestations, including benign lesions such as congenital hypertrophy of the retinal epithelium (CHRPE), jaw cysts, and sebaceous cysts as well as desmoid tumors and other malignancies including periampullary tumors, thyroid cancers, adrenocortical tumors, brain tumors, and hepatoblastomas (1 ). The colorectal features, in association with extra colonic manifestations, are also known as Gardner’s syndrome. A small proportion of patients have an attenuated form of the disease characterized by less than 100 polyps and a later age of onset, known as attenuated adenomatous polyposis coli (AAPC) (2 ). Hereditary desmoid disease is a relatively rare condition characterized by autosomal dominant inheritance of multiple desmoid tumors but with no colorectal polyposis (3 ). In general, the clinical features of the disorder allow a diagnosis of FAP to be made relatively easily. However, the attenuated form of the disease can show similarities to hereditary non-polyposis colon cancer (HNPCC), and mutation analysis of the causative genes may be required to aid in the differential diagnosis.