MUTYH-associated polyposis

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

MUTYH-associated polyposis (MAP) 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). Most people with MAP develop multiple noncancerous (benign) growths (polyps) in the colon by around age 50 years. Polyps can also occur in the small intestine or the stomach. Individuals with this condition can develop ten to hundreds of polyps. Without monitoring and prompt follow-up, affected individuals have an 80 to 90 percent risk of developing colorectal cancer in their lifetimes. However, people with MAP who do not have polyps can also develop cancer.

While colorectal cancer is the most common type of cancer in people with MAP, cancer can develop in other places in the body, including a section of the small intestine known as the duodenum, the breasts, the ovaries, the lining of the uterus (the endometrium), and the bladder. While cancers in other tissues have occurred in people with MAP, it is unclear if the risk for those cancers is higher than the risk for the general population.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the MUTYH gene cause MAP. The MUTYH gene variants that cause MAP are present in all of the body's cells and are known as germline variants. The MUTYH gene provides instructions for making an enzyme that is involved in the repair of DNA. This enzyme corrects particular errors that are made when DNA is copied (DNA replication) in preparation for cell division.

The building blocks of DNA are made up of four chemical bases, each of which pairs with a specific partner to form a unit called a base pair. However, toxic molecules within cells can alter these bases so that they join with the wrong partner. The enzyme produced from the MUTYH gene is part of the repair process that finds and fixes these errors. Once the altered base pairs are fixed, the enzyme will remove the mismatched partner. This process is known as base excision repair.

Variants in the MUTYH gene can cause cells to produce a version of the enzyme that does not function well or at all. As a result, cells are unable to correct DNA mismatch errors. As cells divide, the errors build up in a person's DNA. When these errors occur in genes that control cell growth, cells can grow uncontrollably, which can lead to polyps and the possibility of cancer in people with MAP. For example, the majority of colorectal cancers in people with MAP have a variant in a gene known as KRAS. This KRAS gene variant is an acquired variant that is caused by a MUTYH gene that is not functioning properly.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

MAP is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene. People with only one altered copy of the MUTYH gene likely have a small increase in their risk of developing colorectal cancer compared to the general population, but whether they have an increased risk of other types of cancer is unclear.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of MAP varies from 1 in 20,000 to 1 in 60,000 individuals worldwide. People with MAP account for nearly 1 percent of all people with colorectal cancer.

Which doctor should you see?

The suggested department for discussing MUTYH-associated polyposis is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

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.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for MUTYH-associated 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.