Introduction: Who Should Undergo Diagnostics

Knowing when to seek diagnostic testing for adenomatous polyposis coli, also called familial adenomatous polyposis (FAP), can literally save your life. This condition is inherited, which means it runs in families. If you have a parent, brother, sister, or child with FAP, you are at higher risk of having the condition yourself.^[1] The genetic defect responsible for this disease can be passed down from generation to generation, although in about 25 to 30 percent of cases, the mutation happens spontaneously in someone with no family history.^[1]

Anyone who has a family history of this syndrome should undergo diagnostics starting in childhood. The reason for this early approach is simple: polyps in FAP typically start appearing by the mid-teens, with about 15 percent of people showing signs by age 10, 50 percent by age 15, and 75 percent by age 20.^[11] Without treatment, these polyps will almost certainly turn into cancer by the time a person reaches their 40s.^[1]

People who develop unexplained digestive symptoms should also consider getting tested, especially if they experience rectal bleeding, ongoing diarrhea, or persistent abdominal pain. Rectal bleeding is often the first noticeable symptom, appearing in about 75 percent of patients with FAP.^[19] Even mild symptoms like small amounts of blood in the stool, unexplained weight loss, or fatigue from anemia (a condition where you don’t have enough healthy red blood cells) should prompt a conversation with your doctor about screening.^[19]

Classic Diagnostic Methods

The diagnosis of adenomatous polyposis coli involves several different approaches. Doctors use a combination of physical examinations, visual inspections of the colon, genetic testing, and sometimes imaging studies to confirm the condition and rule out other diseases that might cause similar symptoms.

Flexible Sigmoidoscopy and Colonoscopy

One of the main ways doctors look for FAP is through sigmoidoscopy or colonoscopy. These are procedures where a thin, flexible tube with a camera on the end is inserted into the rectum to view the inside of the large intestine.^[7] During a sigmoidoscopy, the doctor examines the rectum and the lower part of the colon, called the sigmoid colon. This exam can see polyps in the last two feet of the colon.^[7]

For children and teenagers with a family history of FAP, flexible sigmoidoscopy should be performed every one to two years starting at age 10 to 12 years.^[7] This regular screening is designed to catch the first signs of polyp development. Once polyps are detected during sigmoidoscopy, doctors will usually recommend a full colonoscopy, which allows them to examine the entire colon from the rectum all the way to where it meets the small intestine.^[7]

A colonoscopy is more thorough than sigmoidoscopy because it can reveal polyps throughout the entire large intestine. During the procedure, doctors can not only see the polyps but also remove small tissue samples, called biopsies, for further examination under a microscope.^[7] The main sign that doctors look for is hundreds or even thousands of polyps growing in the colon and rectum. In classic FAP, there are typically more than 100 polyps, while in a milder form called attenuated FAP, people usually have fewer polyps, averaging around 20 to 100.^[2]

Upper Gastrointestinal Endoscopy

People with FAP don’t only develop polyps in their colon and rectum. They can also have polyps in their stomach and the upper part of their small intestine, especially in a section called the duodenum.^[1] To check for these polyps, doctors use a procedure called esophagogastroduodenoscopy, or EGD for short. This involves inserting a flexible tube with a camera down the throat to examine the esophagus, stomach, and duodenum.^[7]

Two types of scopes may be used during this examination. A front-viewing scope allows doctors to see the lining of the stomach and duodenum, while a side-viewing scope, called a duodenoscope, is particularly useful for examining the ampulla of Vater, which is the area where the ducts from the liver and pancreas empty into the small intestine.^[7] This area is important to check because polyps here can develop into cancer. The examination should be performed every one to three years once FAP has been diagnosed.^[7]

Genetic Testing

One of the most powerful diagnostic tools for FAP is genetic testing. A simple blood test can reveal whether a person carries the abnormal APC gene that causes the condition.^[7] The APC gene is a tumor suppressor gene, meaning it normally helps prevent cells from growing and dividing too quickly. When this gene is defective, cells can grow out of control, leading to the formation of polyps.^[5]

Genetic testing is especially helpful for children and other family members who may be at risk but haven’t yet developed symptoms. Identifying the gene mutation early allows doctors to start appropriate screening and monitoring. It can also provide relief for those who test negative, sparing them years of worry and unnecessary medical procedures.^[7] For children who do carry the gene, early knowledge allows for timely intervention that can greatly reduce the risk of cancer.^[7]

The test itself is straightforward. A blood sample is taken and sent to a laboratory where specialists look for mutations in the APC gene. Most people with FAP have inherited the mutation from a parent, but in some cases, the mutation occurs spontaneously.^[19] Understanding whether a mutation is present helps doctors and families make informed decisions about monitoring and treatment.

Eye Examination for CHRPE

An unusual but helpful sign of FAP can be found in the eyes. Many people with FAP, up to 80 percent, have flat, dark spots on the retina called congenital hypertrophy of the retinal pigment epithelium, or CHRPE.^[5] These spots don’t affect vision and are completely harmless, but their presence can be a clue that someone has FAP, especially when combined with other signs.^[5]

An eye doctor can see these lesions during a routine eye examination. While CHRPE alone is not enough to diagnose FAP, it can support the diagnosis when other evidence is present, such as a family history or the appearance of polyps during colonoscopy.

Imaging Studies

In addition to endoscopic procedures, doctors may use imaging tests such as computed tomography (CT) scans or magnetic resonance imaging (MRI) to evaluate the abdomen and pelvis.^[7] These scans create detailed pictures of the inside of the body and are particularly useful for detecting desmoid tumors, which are fibrous growths that can occur in people with FAP. Desmoid tumors develop in about 10 to 30 percent of people with the condition and tend to grow in the abdomen or abdominal wall.^[5] Although not cancerous, they can cause problems by pressing on nearby organs.

CT or MRI scans may also help doctors look for tumors in other parts of the body, such as the liver, thyroid, or pancreas, since people with FAP have an increased risk of developing cancers in these areas.^[4]

Distinguishing FAP from Other Conditions

FAP must be differentiated from other conditions that can also cause multiple polyps in the colon. One such condition is Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer. Lynch syndrome increases the risk of colon cancer but typically does not cause hundreds of polyps. People with Lynch syndrome may develop cancer with only one or a few polyps, and the cancer tends to appear a bit later in life than in classic FAP.^[2]

Another condition that can look similar is MYH-associated polyposis (MAP), which is caused by mutations in a different gene. People with MAP also develop multiple polyps, but the inheritance pattern is different—it follows a recessive pattern, meaning a person needs to inherit two defective copies of the gene, one from each parent.^[11] Genetic testing can help distinguish between these conditions.

Diagnostics for Clinical Trial Qualification

When patients with FAP are being considered for enrollment in clinical trials, specific diagnostic tests are often required to ensure they meet the eligibility criteria. Clinical trials are research studies that test new treatments or procedures, and they have strict rules about who can participate.

Confirmed Genetic Mutation

Many clinical trials for FAP require proof of a genetic mutation in the APC gene. This is typically done through the same blood test used for diagnosis.^[7] Confirmation of the mutation ensures that participants truly have the inherited form of the disease and are likely to respond to treatments being tested. Without genetic confirmation, a person might not be eligible for certain trials, even if they have polyps, because the polyps could be caused by something other than FAP.

Colonoscopy Findings

Clinical trials often require a recent colonoscopy to document the number, size, and location of polyps in the colon. Some studies may only accept patients who have a certain number of polyps or who have not yet had surgery to remove their colon. The colonoscopy report provides baseline information that researchers use to measure whether a treatment is working. For example, if a trial is testing a drug designed to shrink polyps, doctors need to know how many polyps were present before treatment started.^[12]

Upper Endoscopy Results

Because FAP also affects the upper digestive tract, some trials may require an upper endoscopy to assess polyps in the stomach or duodenum. This is especially important for studies focused on preventing or treating duodenal cancer, which occurs in about 8 percent of people with FAP.^[2] Researchers may use a staging system to classify the severity of duodenal polyps and determine whether a patient is a good candidate for the trial.

Imaging for Extraintestinal Tumors

Some trials may also require imaging studies such as CT scans or MRIs to check for desmoid tumors or other growths outside the colon. Desmoid tumors can be a significant complication of FAP, and certain trials are designed specifically to test treatments for these tumors. Having a documented desmoid tumor on imaging might be a requirement for participation in such studies.^[7]

Blood Tests and Other Laboratory Work

Clinical trials typically require a range of blood tests to assess overall health and ensure that it is safe for a person to participate. These may include tests to check liver function, kidney function, blood cell counts, and markers of inflammation. Researchers need to know that participants are healthy enough to tolerate the treatment being studied and that any side effects can be distinguished from pre-existing health problems.

Documentation of Family History

Researchers may also want detailed information about your family history, including which relatives have had FAP or colorectal cancer. This information helps scientists understand how the disease is inherited and whether certain patterns are associated with different outcomes. You may be asked to provide medical records from family members or to help create a family pedigree, which is a chart showing how the disease has been passed down through generations.