MUTYHassocierad

MUTYHassocierad, commonly called MUTYH-associated polyposis (MAP), is a hereditary predisposition to colorectal cancer caused by pathogenic variants in both copies of the MUTYH gene. The MUTYH gene encodes a DNA glycosylase that participates in base excision repair of oxidative DNA damage; loss of function in both alleles leads to accumulation of somatic mutations and the development of multiple adenomatous polyps, with an elevated risk of colorectal cancer.

Inheritance is autosomal recessive. Affected individuals have two pathogenic MUTYH alleles, while heterozygous carriers are typically asymptomatic, though some data suggest a modestly increased risk in certain contexts. Mutation types are diverse, but certain common variants have been identified in different populations.

Clinical features vary, with polyp burden ranging from a few to hundreds of adenomas, usually distributed in the colon and rectum. Onset is often in adulthood, and the colorectal cancer risk is substantially higher than in the general population. There is also an elevated risk of duodenal and other gastrointestinal neoplasms, while the extent of extraintestinal cancer risk is less well defined.

Diagnosis is suspected in individuals with multiple adenomas or polyposis without APC mutations (as seen in classic familial adenomatous polyposis). Germline testing for MUTYH variants confirms MAP when biallelic pathogenic mutations are found. Cascade testing of first-degree relatives is recommended upon diagnosis.

Management focuses on surveillance and polyp control. Colonoscopic surveillance typically begins in late adolescence to early adulthood (often around 18–20 years) with intervals of 1–2 years, adjusted to polyp burden. Endoscopic polypectomy is primary; extensive polyposis or refractory disease may necessitate colectomy. Upper GI surveillance for duodenal polyps is advised. Genetic counseling is recommended due to autosomal recessive inheritance.