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Familial adenomatous polyposis

Familial adenomatous polyposis (FAP), due to an alteration in the APC gene, was the first adenomatous polyposis syndrome described.

How common is FAP?

FAP is uncommon. It occurs in 1:10 000 – 1:15 000 of the population, so there are about 6 000 people with FAP in the UK.

What causes FAP?

FAP is caused by an alteration in the APC gene on chromosome 5.

How is FAP inherited?

FAP is dominantly inherited. This means that a person with FAP has a 50% chance of passing on the altered gene, each time they have a child. To explain this, we have 2 copies of each gene in our cells (with a total number of 20 000 genes). One copy is inherited from our father and one from our mother. In the case of FAP, only one of the two APC genes needs to be altered for a person to develop the condition. A person with FAP, therefore, has one altered copy of the APC gene and one unaltered copy. At the point of conception they have a 50% chance of passing on their altered copy and a 50% chance of passing on their unaltered copy.

In at least 10% of people, their FAP is caused by a new genetic alteration (de novo mutation). This means that the alteration has not been passed down from a parent but the person with FAP still has a 50% chance of passing it on to their children.  If FAP is known in a family, then predictive genetic testing will be offered to children of FAP patients between the ages of 12-14. This is usually carried out with a simple blood test.

In around 20% of cases, the genetic alteration causing FAP in a person cannot be found. Usually the person will have a clinical diagnosis of more than 100 adenomatous polyps throughout the large bowel. In this example, family members cannot have a blood test and will be offered colonoscopic screening.

How does FAP affect the bowel?

People with FAP develop polyps inside the large bowel (colon and rectum).  There are a number of different types of polyps and the polyps that people grow in FAP are called adenomas.  An adenoma is a common type of polyp and is usually the type of polyp that develops into bowel cancer in an older person. The difference with FAP is the large number of polyps (100s-1000s) that can grow in the large bowel. These polyps can turn into cancer (over a long period of approximately 20 years), which it is why it is so important to make sure everyone at risk of inheriting FAP is examined. FAP is a serious condition and if left untreated, a person will inevitably go on to develop bowel cancer. This is why having a Polyposis Registry is so important as with early detection FAP can be successfully treated.

Diagram showing the gastrointestinal tract

What is the treatment for the bowel polyps?

FAP is usually clinically diagnosed following a colonoscopy. Large numbers of polyps will be seen and the patient is then referred to their local genetics centre or to us, as the specialist centre, for diagnostic genetic counselling and testing. A genetic test involves the patient having a simple blood test, where the blood is sent to the genetics laboratory in order to extract the DNA and to find out whether a genetic alteration is responsible for the abnormal finding of polyps. If an alteration is found, predictive testing can then be offered to family members who are identified as being at risk.

Rarely, children may develop rectal bleeding at a younger age, necessitating an earlier colonoscopy. Rectal bleeding is the only concerning symptom in a child at risk of developing FAP. As mentioned above, children of parents with FAP will be offered a predictive genetic blood test between the ages of 12-14.

When a person is diagnosed with FAP, they will usually undergo annual colonoscopy with dye spray (so that microadenomas can be detected). When the large bowel polyp count exceeds 100 and/or polyps are at or above 1cm in size, prophylactic surgery will be offered. See our surgery page for what this involves.

Are other parts of the gut affected?

In addition to large bowel polyps, people can also get polyps in the upper gastrointestinal (GI) tract (in the stomach and duodenum). Stomach polyps are usually benign (non-cancerous) fundic gland polyps but occasionally adenomas are found and need removing, so careful inspection of the stomach is very important. The duodenum and ampulla are the areas where most upper GI adenomas are found. These polyps are momitored via a camera test or endoscopy called a gastroscopy or OGD, where the camera is passed via the mouth and throat. Surveillance usually starts from the age of 25 and a staging system called The Spigelman Staging system is used to decide on how often the procedure should be repeated (usually 5, 3 or 1 yearly). In a small percentage of cases, preventative surgery is also required for the upper GI tract. This surgery is known as a pancreaticoduodenectomy or Whipple procedure.

Diagram showing the anatomy of the stomach, duodenum and ampulla

Can any other parts of the body be involved?

There are a number of ‘extra-intestinal’ manifestations (problems that occur outside the GI tract) associated with FAP:-

Desmoids

A desmoid (sometimes referred to as a myofibroblast tumour) is not a cancer as it cannot spread to other parts of the body but it can grow locally and requires careful monitoring and treatment. They can be seen in the general population but are much more common in FAP, affecting 10-15% of FAP patients. Most of FAP-associated desmoids are intra-abdominal, where they occur predominantly in the small bowel mesentery.  Most people with a desmoid tumour can be managed conservatively with little effect on quality of life. A small proportion of patients will need treatment in the form of drug therapy and sometimes surgery. Desmoids can have an unpredicatable nature which can make management difficult. Attempted surgical resection can be very difficult and may stimulate surgical growth and should only be attempted in a specialist centre.

Osteomas

Harmeless bony lumps, especially on the skull and jawbone. Usually best left unless they are in a very awkward place as the scarring from removal can cause more trouble than the osteoma itself.

Sebaceous cysts

These are very common in the general population, but even more common in people with FAP. They are harmless skin cysts, but can be unsightly and sometimes get infected. They can usually be removed very easily under local anaesthetic.

CHRPE(congenital hypertrophy of the retinal pigment epitheliam)

Often noted during an eye test, CHRPE are harmless black plaques found on the back of the retina. They can be seen in the general population but bilateral CHRPE may be more commonly noted in FAP.

Other cancers

As well as bowel, duodenal and ampullary cancer, having FAP may lead to an increased risk of certain other cancers such as thyroid cancer, childhood hepatoblastoma, adrenal adenoma and CNS tumours. These cancers remain rare in an uncommon condition.