Background Information
Familial adenomatous polyposis (FAP) is an autosomal dominant condition
affecting nearly 1 in 5000 people. It is characterised by the progressive
development of hundreds to thousands of adenomatous colon polyps, some of which
inevitably progress to carcinoma if the colon is not surgically removed. Age of
onset of polyp development can be as early as 11 or 12, and malignant
transformation can occur as late as the 7th decade. As classically defined, FAP
has no associated extracolonic manifestations. However, there is at least one
syndrome complex that is allelic to FAP: Gardner
syndrome. Features of Gardner
syndrome include colonic polyposis, polyps of the stomach and small intestine,
globoid osteoma especially of the mandible and calvarium, congenital
hypertrophy of the retinal pigment epithelium, epidermoid cysts and desmoid
tumours. Rarely, adrenal carcinoma, thyroid carcinoma, periampullary carcinoma
and hepatoblastoma (especially in children under age 4) can be seen in patients
with FAP/Gardner. A second condition, Turcot syndrome, may be related to
FAP. It is characterised by colonic polyposis and brain tumours
(gliomas).
The disease frequency for this documented condition is 1 in 5000 and an
estimated 2 in 5000 individuals are at 50% risk for the disorder. Cancer
surveillance for at risk individuals includes annual colonoscopy and upper
gastrointestinal endoscopy, annual examination of the skin and annual
comprehensive physical including palpation of the thyroid.
APC
-associated polyposis conditions are caused by mutations in the
APC
gene.
Molecular genetic testing of
APC
detects disease-causing mutations in up to 95%
of probands with typical FAP. Molecular genetic testing is most often used in
the early diagnosis of at-risk family members and in the confirmation of the
diagnosis of FAP or attenuated FAP in individuals with equivocal findings
(e.g., fewer than 100 adenomatous polyps).
Molecular genetic testing for
APC
is
available.
