MUTYH polyposis is caused by germline mutations of the MUTYH gene, a base excision repair gene. The most common variants are Y179C and G396D (1). Affected patients are homozygous or compound heterozygous. About 1% of the population carries one of the mutations.
Affected patients usually present with numerous colon polyps at 60 to 70 years of age, and more than half present with colorectal cancer. The disorder is present in 7 to 40% of patients who have > 10 adenomas.
In addition to colon cancer, affected individuals are at increased risk of gastroduodenal adenomas, osteomas, desmoid tumors, Muir-Torre phenotype with sebaceous gland tumors, and congenital hypertrophy of the retinal pigment epithelium (a feature also occurring in patients with familial adenomatous polyposis). Affected individuals are also at risk of developing cancer of the ovary, bladder, thyroid, and skin.
(See also the American College of Gastroenterology's clinical guideline on the genetic testing and management of hereditary gastrointestinal cancer syndromes.)
Genetic testing is required to establish the diagnosis.
Testing the spouse of an affected patient for the MUTYH gene may be cost-effective; if the spouse is heterozygous, their children should then have genetic testing for this disorder.
Affected patients should have surveillance colonoscopy every 1 to 2 years starting at age 25 to 30. They should have upper endoscopy starting at age 30 to 35. The frequency of this test depends on the presence of gastroduodenal polyps. Fundic gland polyps should be biopsied for dysplasia.
Annual thyroid screening with physical examination and ultrasonography is also recommended. Patients also require surveillance for ovarian, bladder, and skin cancers.
Monoallelic carriers are screened for colorectal cancer with colonoscopy every 5 years beginning at age 40 (similar to a person who has a first-degree relative with colorectal cancer).
Endoscopic management (eg, polypectomy, mucosal resection) is the main treatment of MUTYH polyposis syndrome.
If cancer is present or the polyp burden is too large, surgical resection is needed. Partial, subtotal, or total colectomy are the surgical options, depending on the extent and burden of disease.