Familial Adenomatous Polyposis (FAP)

What is familial adenomatous polyposis (FAP)?

Familial adenomatous polyposis is a genetic disorder that predisposes you to develop precancerous colon polyps called adenomas. Colon polyps are abnormal growths in the lining of your colon or rectum. They aren’t cancer, but certain types, like adenomas, can change into colorectal cancer.

Many people get a few colon polyps at random as they get older. But if you have a hereditary polyposis syndrome like FAP, you’ll develop many colon polyps — typically over a hundred — starting from a young age. This significantly raises your lifetime risk that one of them will become cancerous.

To manage this risk, healthcare providers usually recommend complete removal of the colon (total colectomy) and sometimes the rectum, too (proctocolectomy). Polyps in FAP appear too frequently to manage them one by one. Without surgery, most people with FAP will develop cancer by their middle-age years.

People with FAP may also develop polyps in other organs, and other abnormal growths in places like their skin, soft tissues, teeth and bones. Even after colectomy surgery, they’ll need to continue to have regular screenings for other tumors, and possibly additional surgeries to manage those tumors.

What is the estimated cancer risk with familial adenomatous polyposis?

Without treatment, the risk of developing colorectal cancer with familial adenomatous polyposis is close to 100%. It also develops relatively earlier and faster with FAP than in those without. Children in families known to be affected by the syndrome begin yearly colonoscopy screenings at the age of 10.

Besides colorectal cancer, people with familial adenomatous polyposis also have an increased risk of developing other cancers, including:

• Duodenal cancer (8%).
• Papillary thyroid cancer (2%).
• Pancreatic cancer (2%).
• Hepatoblastoma (1.5%).
• Stomach cancer (1%). 
• Brain and spinal tumors (less than 1%).

Are there different types of FAP?

Familial adenomatous polyposis has a classic form and some less common forms that are considered subtypes.

• “Classic” FAP is characterized by more than 100 adenomatous polyps in your colon.
• “Attenuated” FAP (AFAP) is a less severe subtype in which you have somewhere between 20 and 100 colon polyps.
• Gardner syndrome, like classic FAP, typically involves over a hundred colon polyps, as well as other types of tumors in other body parts. 
• Turcot syndrome involves multiple colon polyps, as well as one cancerous brain tumor. 

How common is familial adenomatous polyposis?

Familial adenomatous polyposis is rare, estimated to affect about 1 in 8,000 people. It accounts for only about 0.5% of all colorectal cancer cases. Variants like AFAP, Gardner syndrome and Turcot syndrome are rarer. They represent between 5% and 10% of all familial adenomatous polyposis cases.

What’s the difference between familial adenomatous polyposis (FAP) vs. Lynch syndrome?

Lynch syndrome is a different hereditary syndrome that can raise your risk of developing colorectal cancer and other cancers. Lynch syndrome is also sometimes called hereditary nonpolyposis colorectal cancer syndrome (HNPCC). As the name suggests, it doesn’t necessarily cause a lot of colon polyps.

People with Lynch syndrome may develop colorectal cancer with only one or a few colon polyps. Polyps and cancer also tend to develop a little later than in classic FAP, and the lifetime risk is a bit lower. Different gene mutations lead to the differences between Lynch Syndrome and FAP.

What are the signs and symptoms of familial adenomatous polyposis (FAP)?

Colon polyps in FAP begin to appear much earlier than in the general population, often during the teenage years. They usually won’t cause symptoms until they’ve grown large enough to be dangerous. But if you have a colonoscopy for screening purposes, your healthcare provider will find them. 

People with FAP often have hundreds or thousands of colon polyps. Those with AFAP have at least 20. The greater number and faster growth of polyps in FAP may make them more likely to cause symptoms than polyps usually are. Symptoms may include rectal bleeding, diarrhea or chronic abdominal pain.

People with FAP may also have superficial lesions that healthcare providers can observe, such as:

• Dermatofibromas, fibrous, scar-like lumps just under the skin.
• Epidermal cysts, dome-shaped lumps filled with keratin just under the skin.
• Osteomas, benign bone tumors, often visible on the jawbone or skull.
• Extra teeth or impacted teeth (visible on a dental X-ray).
• Pigmented lesions on the retina of the eye (congenital hypertrophy of the retinal pigment epithelium, or CHRPE), visible on an eye exam. They usually don’t cause vision problems.

What is the average age of onset of familial adenomatous polyposis symptoms?

Colon polyps in FAP begin to appear at the average age of 16. They occur a little later with AFAP. If your parents and healthcare provider know that you’re at risk for the syndrome, they’ll likely begin screening after you turn 10. If they don’t know, it might be your symptoms that bring the condition to light.

What is the main cause of familial adenomatous polyposis?

Familial adenomatous polyposis is caused by a gene mutation. The gene is called adenomatous polyposis coli, or APC. It’s a tumor suppressor gene, which means it’s supposed to prevent cells from growing out of control and forming tumors. The mutation interferes with the function of the gene.

The gene mutation that causes FAP is a germline mutation, which means it occurs during conception, not during your lifetime. This is how it runs in families. If one of your parents has the mutation, you have a 50% chance of inheriting it. However, up to 30% of these mutations are original, not inherited. This means that about 30% of patients diagnosed with FAP won’t have a family history of the disease.

What are the complications of familial adenomatous polyposis?

Colorectal cancer is the most important complication to manage with FAP. Surgery to remove your colon drastically lowers this risk. But living without a colon will complicate your life, to a lesser extent, by changing the way you poop. You’ll have to replace your colon with either an ileostomy pouch or an ileal pouch.

Since the gene mutation that causes FAP is in every cell of your body, tumors can also occur throughout your body. You may develop other tumors outside of your colon, which can sometimes become cancerous. Your healthcare provider will recommend a screening schedule to check for these tumors:

• Duodenal/periampullary polyps. These polyps occur in your duodenum, the top part of your small intestine, or in your bile duct or pancreatic duct where they join the duodenum. Almost everyone with FAP will get them. A few may develop duodenal cancer, ampullary cancer, pancreatic cancer (in the duct) or bile duct cancer.
• Stomach polyps. Up to 90% of people with FAP get stomach polyps, but only 1% of these polyps become cancerous.
• Desmoid tumors. These benign connective tissue tumors occur in about 15% of people with FAP. They can cause health problems and even death in up to 5%. While they aren’t cancerous, they can be aggressive and grow into neighboring structures, compressing or obstructing blood vessels, organs and nerves. They can be difficult to remove, and they often come back.
• Papillary thyroid cancer. This thyroid cancer occurs in up to 2% of people with FAP. It’s relatively benign and almost always curable.
• Liver cancer. Children with FAP, in particular, are at a slightly increased risk of developing hepatoblastoma, a rare liver tumor.
• Medulloblastoma. This cancerous brain tumor can develop with FAP-associated Turcot syndrome. It’s rare, even with FAP.
• Rectal polyps. If you don’t have your rectum removed with your colon, you’ll remain at risk of developing rectal polyps. You’ll have to continue with regular proctoscopy screenings for life.

How do you know if you have familial adenomatous polyposis?

If you want to know if you’ve inherited the APC gene mutation, you can find out through genetic testing. A genetic test takes a DNA sample (such as blood or saliva) and looks for specific gene mutations. If you do have the mutation, the next step is a colonoscopy to check for adenomas. 

Diagnosis of FAP is based on having at least 100 polyps, or 20 for AFAP, and the APC mutation. Familial adenomatous polyposis isn’t the only hereditary syndrome that can cause adenomatous colon polyps. MUTYH-associated polyposis is a similar syndrome caused by a different mutation, in the MUTYH gene. 

What is the treatment plan for familial adenomatous polyposis?

Treatment for FAP involves lifelong surveillance and, eventually, surgery. In the beginning, if you have fewer polyps (or AFAP), your provider might be able to remove them individually during colonoscopy screenings (polypectomy). You’ll need surgery when there are too many or they become cancerous.

Surgery

Most people with classic FAP will have a total colectomy sometime in their late teens to early thirties. Your healthcare provider will determine when to schedule your surgery based on your particular risk factors. They’ll also discuss with you the different types of colectomy operations you might have.

When you have your colon removed, there will be a gap between your small intestine and your rectum (or anus). Sometimes, a surgeon can reconnect these ends together so you can continue pooping out your anus (butthole). If not, they’ll create an ostomy, a new opening in your abdomen for your poop to come out. 

Screening

Your healthcare team will advise you on how often to get screening tests for different types of tumors based on your personal risk factors. For classic FAP, guidelines recommend yearly colonoscopies starting at age 10 and continuing until your colectomy. For AFAP, yearly screenings should begin by age 20.

After your colectomy, you’ll need to continue with regular sigmoidoscopies, examinations of the end of your GI (gastrointestinal) tract. If you have some rectum left over, it should be checked every six to 12 months. If your rectum was removed but was replaced by an ileal pouch, it should be checked every one to four years.

Other regular screenings may include:

• Upper endoscopy. This is like a colonoscopy, but for the upper end of your GI tract. The endoscope passes down your throat and into your stomach and duodenum to check for polyps there. If it finds any, your healthcare provider can remove them during the procedure.
• Ultrasound to screen for thyroid or liver cancers.
• CT scan (computed tomography scan) or MRI (magnetic resonance imaging) to screen for desmoid tumors.

Can familial adenomatous polyposis be prevented?

Genetic counseling can help you understand the risks of passing on FAP to your genetic descendants. Discussing these risks can help you plan. In general, you can’t prevent the gene mutation from happening at conception, but there are some different family planning options you can consider.

What is the life expectancy of someone with familial adenomatous polyposis?

Without timely treatment, the median life expectancy is 42 years. But with appropriate care, you can live a normal life. Once your colon has been removed, your biggest risk is from other gastrointestinal cancers or problematic desmoid tumors. These occur much less frequently than colorectal cancer.

What can I expect if I have this condition?

If you’re diagnosed with FAP, you can expect a lifetime of medical screenings and possibly multiple surgeries to remove tumors. Tumors outside of your colon are less likely to become cancerous than colon polyps. Desmoid tumors, which aren’t cancerous, can be a minor irritation or a major one.

You can expect to have a total colectomy sometime in your early life. You may be able to have your bowels reconnected afterward, or you may have an ileal pouch or an ostomy. All options come with some risks of specific complications. But you can live a long and healthy life after a colectomy.