MUTYH-related polyposis

MUTYH-associated polyposis (MAP), also known as MUTYH-related polyposis or MYH-associated polyposis, is an inherited colorectal polyposis syndrome caused by biallelic (two-copy) pathogenic variants in the MUTYH gene. The MUTYH gene encodes a DNA glycosylase involved in base excision repair, specifically correcting oxidative DNA damage. When both copies of this gene are nonfunctional, cells accumulate somatic mutations—particularly G:C to T:A transversions in genes such as APC and KRAS—leading to the development of multiple colorectal adenomatous polyps and a significantly increased risk of colorectal cancer. Affected individuals typically develop between 10 and a few hundred colorectal adenomatous polyps, usually presenting in adulthood, most commonly between the ages of 40 and 60. The phenotype can resemble attenuated familial adenomatous polyposis (AFAP). In addition to colorectal polyps and cancer, individuals with MAP may have an increased risk of duodenal adenomas and duodenal cancer, as well as modestly elevated risks for ovarian, bladder, and skin cancers. Some patients may also develop serrated polyps or hyperplastic polyps alongside classical adenomas. Extraintestinal features such as osteomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and desmoid tumors are generally not associated with MAP, which helps distinguish it from classic FAP. Management of MAP centers on regular colonoscopic surveillance, typically beginning between ages 25 and 30, with polypectomy of identified adenomas. Upper gastrointestinal endoscopy is also recommended to screen for duodenal polyps. When the polyp burden becomes too great to manage endoscopically, or if colorectal cancer is detected, surgical intervention such as colectomy or proctocolectomy may be necessary. Genetic counseling is important for affected individuals and their families, particularly regarding the autosomal recessive inheritance pattern, which means siblings of affected individuals have a 25% chance of also being affected. Monoallelic (heterozygous) MUTYH carriers may have a modestly increased colorectal cancer risk, though this remains an area of ongoing research.

Common questions about MUTYH-related polyposis