Familial Adenomatous Polyposis and the APC gene

Familial Adenomatous Polyposis and the APC gene

Familial Adenomatous Polyposis (FAP), as the name suggests, causes polyps. It affects 1 in 7,000 to 1 in 22,000 people.

In the classic form, 100 to 1000s of polyps develop in the colon (bowel). The polyps start appearing in the early teens and left untreated these polyps almost always become cancerous. The classical form is associated with a phenotype that includes desmoids, cysts in the jaw (osteomas), changes in the eye (CHRPE) and polyps elsewhere in the gastrointestinal tract.

There is also a milder form called attenuated FAP (AFAP). Here, 10s to 100s of polyps develop, usually appearing at a later age and there are usually no other signs or symptoms.

Before it was know that inherited mutations in the APC gene were responsible, Familial Adenomatous Polyposis syndrome was known by other names, based on the clinical features:

Gardner syndrome is a clinical syndrome used to describes families with multiple bowel polyps (adenomas of the colon) and skin lumps such as epidermoid cysts, lipomas as well as desmoids (tumour of the connective tissues) and osteomas (benign bone growths, often found in the jaw). It's an old term and no longer used. Gardner syndrome also applied to families with Lynch syndrome who had sebaceous adenocarcinomas of the skin.

Turcot syndrome is a clinical syndrome used to describe families with had multiple bowel polyps (adenomas of the colon) and brain tumours. When the genetic cause is an APC mutation, such as in Familial Adenomatous Polyposis syndrome, the brain tumours are usually medulloblastoma. Turcot syndrome also applied to families with Lynch syndrome but in these families the brain tumours were usually glioblastoma.

A particular mutation in the APC gene, written APC c.3920T>A p.(Ile1307Lys), is common in people of Ashkenazi descent. Rather than switching on the APC gene and causing multiple polyps to grow, this mutation increases the chance that more mistakes will occur in that person in the APC gene itself over time. It occurs in ~6 to 11% of individuals with Ashkenazi heritage. In this population it increases the risk of colorectal cancer. guidelines recommed starting bowel cancer screening with faecal occult blood testing (FOBT) at age 40 and commencing colonoscopy screening every 5 years from age 50.

FAP management

ZZZ still to be completed

There is a 50% chance of a person who carries a germline ATM mutation, whether male or female, passing the mutation to their son or daughter. If a mutation is identified, then predictive testing is available for blood relatives.

Does this sound like you or your family? Has an FLCN mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.

These links may be useful

  • We haven't found a specific Australian Support Group for this syndrome yet. However, FAP Gene Support Group is based in the UK and has good resources
  • The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines
  • The US National Library of Medicine website has more information about this syndrome.