Overview of Familial Adenomatous Polyposis

What Is Familial Adenomatous Polyposis (FAP)?

Familial Adenomatous Polyposis (FAP) is a rare, inherited disorder that significantly increases the risk of developing colorectal cancer. Individuals with FAP typically develop hundreds to thousands of noncancerous polyps—also known as adenomas—primarily in the colon and rectum. Without medical intervention, these polyps nearly always progress to cancer over time.

Prevalence and Other Names for FAP

FAP is estimated to occur in 1 out of every 8,000 to 18,000 individuals and accounts for less than 1% of all colorectal cancer cases in the United States. It contributes to about 0.5% of total colon cancer cases. Alternate names for FAP include:

• Adenomatous polyposis of the colon (APC)

• Familial multiple polyposis

• Hereditary polyposis coli

• Multiple polyposis of the colon

Genetic Causes and Inheritance Pattern

FAP is an autosomal dominant condition, meaning a person only needs one copy of the mutated gene to inherit the disorder. A parent with FAP has a 50% chance of passing the mutation to each child. Polyps generally begin to appear during adolescence, and if not treated, often develop into cancer by the age of 39.

Attenuated FAP

A milder form known as attenuated familial adenomatous polyposis involves fewer polyps—typically between 10 and 100—and has a later onset of cancer, often around age 55.

Early Signs and Symptoms

Many individuals with FAP may remain symptom-free for years, despite having multiple polyps. When symptoms do appear, they may include:

• Rectal bleeding or blood in the stool

• Unexplained weight loss

• Abdominal discomfort or pain

• Changes in bowel habits, including stool consistency or frequency

Adenomatous Polyps and Risk of Cancer

The polyps seen in FAP are adenomatous, meaning they are initially benign but considered precancerous. These typically start forming around age 16. Although the colon is the primary site for these growths, polyps and tumors can also appear in other parts of the body, including:

• Small intestine (especially the duodenum)

• Stomach (desmoid tumors)

• Brain and central nervous system

• Thyroid gland

• Skin

• Eyes

Gardner’s Syndrome

When FAP is accompanied by tumors in areas beyond the colon—such as the skin, bones (osteomas), or eyes—it may be referred to as Gardner’s Syndrome. This variation also presents with additional symptoms like:

• Dental abnormalities (extra or missing teeth)

• Congenital hypertrophy of the retinal pigment epithelium (CHRPE), visible as dark spots in the eye from birth

Associated Cancers

In addition to colorectal cancer, FAP increases the risk of other malignancies, including:

• Pancreatic cancer

• Hepatoblastoma (a rare liver cancer in children)

• Papillary thyroid cancer

• Bile duct cancer

• Stomach cancer

• Brain and spinal cord tumors

When Surgery Is Necessary

If FAP is not treated—often by surgically removing part or all of the colon (colectomy)—the likelihood of cancer developing in a person’s 30s or 40s becomes extremely high. Early medical intervention is crucial.

APC Gene Mutation: The Root Cause

FAP is typically caused by mutations in the APC gene (adenomatous polyposis coli). This gene is responsible for producing a protein that regulates cell growth. When it mutates, the protein can no longer suppress cell division effectively, leading to uncontrolled cell growth and polyp formation.

MYH-Associated Polyposis (MAP)

A different, recessively inherited form of FAP known as MYH-associated polyposis (MAP) results from mutations in the MUTYH gene. This variant tends to be less severe and involves fewer than 100 polyps.

Who Is at Risk?

The main risk factor is having a first-degree relative with FAP. However, spontaneous (de novo) gene mutations can also cause the condition in individuals without any family history. Screening often begins between ages 10 and 12 for those at risk, and later for those with suspected attenuated FAP.

Diagnostic Methods for FAP

To confirm a diagnosis, doctors may use several tests based on symptoms and family history. If a person has between 10 and 20 colorectal adenomas—along with other FAP-related symptoms like CHRPE or desmoid tumors—FAP is usually suspected.

How the Colon Is Examined

Several medical procedures are used to examine the colon and detect polyps:

Colonoscopy

A colonoscopy uses a long, flexible tube with a camera to examine the entire colon and rectum. Patients need to follow a special diet and use laxatives beforehand. Sedation is typically given for comfort. If numerous polyps are found, a diagnosis of FAP may be made. Tissue samples (biopsies) may also be taken during the procedure.

Sigmoidoscopy

This procedure is similar to a colonoscopy but only examines the lower part of the colon using a shorter scope. It’s often less invasive and requires minimal bowel preparation.

CT Colonography (Virtual Colonoscopy)

Also known as CT Pneumocolon or VC, this imaging test uses CT scans to provide detailed views of the colon and rectum. Air or carbon dioxide is introduced into the colon to enhance image clarity. Sedation is not required for this method.