MUTYHassociated

MUTYH-associated polyposis (MAP) is an inherited colorectal cancer predisposition syndrome caused by biallelic pathogenic variants in the MUTYH gene. It is characterized by multiple colorectal adenomas and an elevated risk of colorectal cancer, with the polyp burden typically ranging from a few dozen to a few hundred. MAP is considered in individuals with a polyposis phenotype when APC gene testing is negative or when the family history suggests an autosomal recessive pattern.

The MUTYH gene encodes a DNA glycosylase that participates in base excision repair, removing misincorporated adenines opposite 8-oxoguanine and helping prevent G:C to T:A transversions. Pathogenic variants that disrupt this function lead to accumulation of mutations and increased colorectal neoplasia. In MAP, cancer risk may be influenced by the specific mutations and other genetic or environmental factors. Heterozygous carriers of a MUTYH pathogenic variant have been studied for potential modest risk increases, but the level of risk is not as clearly defined as in biallelic carriers.

Inheritance is autosomal recessive, so affected individuals typically have two mutated MUTYH alleles, often with affected siblings or a consanguineous background. Some families may present with fewer polyps and later onset, while others resemble colonic polyposis conditions with higher cancer risk. Extra-colonic involvement is less common but can occur, including upper gastrointestinal polyps in some cases.

Diagnosis is established by genetic testing showing two pathogenic MUTYH variants. Testing is recommended for individuals with multiple colorectal adenomas, a positive family history consistent with MAP, or when monoallelic MUTYH carriage prompts cascade testing in relatives. Management centers on intensified colonoscopic surveillance, timely polypectomy, and consideration of colectomy in cases of numerous polyps or cancer. Upper GI surveillance may be guided by polyp presence.