Familial adenomatous polyposis

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Familial adenomatous polyposis (FAP) is an inherited disorder that is characterized by a greatly increased risk of cancer of the large intestine (colon) and rectum (collectively known as colorectal cancer). People with FAP have multiple precancerous (benign) growths (polyps) in the colon, and one or more of these polyps will likely develop into colorectal cancer. There are two forms of FAP: the classic type and the attenuated type.

The classic type of FAP is the more severe type. People with classic FAP develop colon polyps as early as childhood. By age 35 years, 95 percent of people with classic FAP will have colon polyps. Once polyps appear in people with classic FAP, the number of polyps increases quickly. People with classic FAP may have hundreds to thousands of colon polyps. Unless the colon is removed, one or more of these polyps will become cancerous (malignant). Individuals with classic FAP typically develop colorectal cancer around 40 years old, and at least 90 percent of affected individuals will develop colorectal cancer by age 50 years if they do not have a procedure that removes their colon beforehand (preventative colectomy).

The attenuated type of FAP is the less severe form. People with attenuated FAP tend to have fewer polyps (an average of 30) that develop later in life (early to mid-adulthood) than those with classic FAP. People with attenuated FAP have a 70 percent lifetime risk of colorectal cancer, with cancer typically developing around 55 years old. People with attenuated FAP may or may not be advised to have a preventative colectomy.

Less commonly, people with FAP may develop other types of cancer. Affected individuals are at increased risk of developing cancer of the stomach, pancreas, a gland in the lower neck (thyroid gland), liver (specifically, a form known as hepatoblastoma), brain (specifically, a form known as medulloblastoma), or a section of the small intestine (duodenum).

People with FAP can also have benign growths in their bones (osteomas), in their skin (cysts), or in the small glands located on top of the kidneys called adrenal glands (adrenal masses). Other benign growths called desmoid tumors develop in 10 to 30 percent of people with FAP. These fibrous tumors usually occur in the abdomen or abdominal wall. Desmoid tumors tend to recur after they are surgically removed.

People with FAP may also have dental abnormalities, which can include teeth that do not break through the gums, one or more missing teeth, extra (supernumerary) teeth, and dental cysts.

Individuals with FAP often have an eye problem called congenital hypertrophy of the retinal pigment epithelium (CHRPE). CHRPE is characterized by flat lesions on the light-sensitive tissue that lines the back of the eye (retina) that can be seen during an eye exam. CHRPE does not cause any vision problems and occurs in up to 80 percent of people with FAP.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the APC gene cause FAP. The APC gene provides instructions for making a protein that acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. In particular, the APC protein helps block a signaling pathway that promotes cell growth and division. The APC protein also interacts with parts of the cell to help ensure that the number of chromosomes in a cell is correct after the cell divides.

Most of the APC gene variants that cause FAP lead to the production of an abnormally short, nonfunctional version of the APC protein. This shortened protein cannot block the signaling pathway, so cell growth is not controlled. This cell overgrowth leads to the colon polyps, tumors, and colorectal cancer seen in people with FAP. Additionally, the nonfunctional APC protein can impair normal cell division, which may result in an abnormal number of chromosomes in cells and contribute to cancer development in people with FAP.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

FAP is inherited in an autosomal dominant pattern, which means one copy of the altered APC gene in each cell is sufficient to cause the disorder. Affected individuals have a 50 percent chance of passing on the APC gene variant to each child. In 75 to 80 percent of cases, an affected person has one parent with FAP.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

FAP has an incidence of 1 in 8,500 individuals. FAP accounts for about 0.5 percent of all cases of colorectal cancer.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Adenomatous colonic polyposis · Very frequent (99-80%)

Presence of multiple adenomatous polyps in the colon.

Colorectal polyposis · Very frequent (99-80%)

Multiple abnormal growths that arise from the lining of the large intestine (colon or rectum) and protrude into the intestinal lumen.

Congenital hypertrophy of retinal pigment epithelium · Very frequent (99-80%)

Sharply demarcated, congenital hyperpigmentation of the retinal pigment epithelium. It can be solitary, clustered or multifocal, uni- or bilateral.

Desmoid tumors · Very frequent (99-80%)

Benign, slow-growing tumors without any metastatic potential. Despite their benign nature, they can damage nearby structures causing organ dysfunction. Histologically they resemble low-grade fibrosarcomas, but they are very locally aggressive and tend to recur even after complete resection. There is a tendency for recurrence in the setting of prior surgery and the most common localisation of these tumors is intraabdominal from smooth muscle cells of the instestine.

Neoplasm of the gastrointestinal tract · Very frequent (99-80%)

A tumor (abnormal growth of tissue) of the gastrointestinal tract.

Colon cancer · Very frequent (99-80%)

Abnormality of the dentition · Frequent (79-30%)

Any abnormality of the teeth.

Constipation · Frequent (79-30%)

Infrequent or difficult evacuation of feces.

Other findings in the same source

From: Orphanet

Additional reported features include Diarrhea (Frequent (79-30%)); Duodenal polyposis (Frequent (79-30%)); Osteoma (Frequent (79-30%)); Thyroid nodule (Frequent (79-30%)); Multiple gastric polyps (Frequent (79-30%)); Abnormality of the cementum (Occasional (29-5%)); Abnormality of the thyroid gland (Occasional (29-5%)); Adrenocortical adenoma (Occasional (29-5%)); Angiofibromas (Occasional (29-5%)); Duodenal adenocarcinoma (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Familial adenomatous polyposis is Gastroenterology, with a gastroenterologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which digestive symptoms or nutritional changes matter most?
• What question would an endoscopy, scan or laboratory test answer if one is proposed?
• How should persistent pain, bleeding or difficulty eating be followed up?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Familial adenomatous polyposis. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.