Familial Adenomatous Polyposis (FAP)

An uncommon but important condition where patients are at almost certain risk of bowel cancer if untreated.


FAP is due to germline mutation of the APC (Adenomatous Polyposis Coli) gene. About 25% of cases are sporadic germline mutations (ie. no family history).
When both copies of APC are lost (which also occurs, albeit at a later age, in the more common sporadic bowel cancer) the function of APC is lost. APC promotes degredation of beta-catenin, and in its absence beta-catenin accumulates in the cell. It is believed to activate the WNT pathway (Wingless) which in turn inhibits apoptosis and terminal differentation, thereby allowing polyps to form.

Clinical Features

Patients with FAP typically have hundreds to thousands of polyps within the large bowel; patients with a family history who are screened may be found with fewer polyps. The polyps begin emerging between 10-30 in most cases. Some of these polyps eventually progress to invasive cancer in a similar way to non-FAP polyps do.
Less common features of FAP include:

  • Polyps of the gastrointestinal tract outside the colon and rectum (40-80% of cases)
  • Thyroid cancer (3%), hepatoblastoma (1%) or medulloblastoma (< 1%)
  • Desmoid tumours (10-25% of patients, known as Gardner syndrome)

There are several eponymous syndromes that share features with FAP:

  • Turcot syndrome is a variant of FAP and describes the cases of patients with bowel cancer and brain tumours. In FAP, most brain tumours will be medulloblastomas. Turcot syndrome also occurs with Lynch syndrome (HNPCC), although the typical tumour is glioma in that setting.
  • Gardner syndrome is a variant of FAP which is also due to mutation of APC. Patients suffer a number of extra-colonic conditions, most commonly desmoid tumours, sebaceous cysts, lipomas and osteomas. Gardner syndrome is not truly separable from FAP and there is no identified difference in the mutations that cause FAP or Gardner syndrome.


Patients with known APC mutation in the family should be screened from a young age (10) and offered total colectomy once polyps develop.
Management of associated conditions is more complex.

  • Upper GI surveillance is usually recommended; if negative then repeat imaging in 5 years is performed
  • Desmoid tumours typically occur in the abdomen and may be fatal due to multiple recurrences and destruction of the mesenteric blood supply. As patients with FAP live longer, these tumours are becoming increasingly frequent. Surveillance for these tumours has no known benefit