Clinical Guidance

Functional studies have shown differences in glycosylase activity between the pathogenic variant and the pathogenic variant . Differences were also seen in clinical manifestations: homozygosity for was associated with a more severe phenotype and an approximately eight-year-earlier age of onset compared to homozygosity for [, , , ]. For other common variants, such as p.Glu324His, which has up to a 50% minor allele frequency in some populations , association with cancer risk has been reported; however, the reported risks are not consistent with mendelian inheritance and are not used to direct patient care.

Source: GeneReviews — "MUTYH Polyposis"

Diagnostic Criteria

Suggestive Findings

MUTYH polyposis (MAP) should be suspected in an individual with the following clinical findings and family history .

Clinical findings

Source: GeneReviews — "MUTYH Polyposis"

Differential Diagnosis

MUTYH polyposis (MAP) can be distinguished from other inherited polyposis and colon cancer conditions by clinical findings, pathologic findings, mode of inheritance, and molecular genetic testing. Conditions to consider in the differential diagnosis include the disorders summarized in . Table 5. Disorders to Consider in the Differential Diagnosis of MUTYH Polyposis

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with MUTYH polyposis (MAP), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Review of personal medical history with emphasis on those features related to MAP or colorectal cancer (CRC): colon polyps (majority are adenomas), rectal bleeding, abdominal pain and discomfort, bloating, diarrhea

• Colonoscopy and review of pathology

• Baseline upper endoscopy including visualization of the major ampulla starting at age 30-35 years

• Baseline thyroid ultrasound examination

• Consider skin examination by a dermatologist.

• Consultation with a clinical geneticist and/or genetic counselor

Currently, investigations for other extracolonic manifestations of MAP are not recommended at the time of initial diagnosis.

Treatment of Manifestations

Practice parameters, including information on surgery, have been outlined by the following resources:

• National Comprehensive Cancer Network

• American College of Gastroenterology (full text)

• American Society of Colon and Rectal Surgeons

• American Society of Clinical Oncology (full text)

• Society of Surgical Oncology (full text)

Source: GeneReviews — "MUTYH Polyposis"

Clinical Guidance

Currently, no studies have investigated external factors or lifestyle factors that could affect the severity of the manifestations of MUTYH polyposis. Smoking may affect polyp development based on a case report of monozygotic twins with MAP in which a somewhat more severe phenotype was observed in the sister who smoked compared to her twin sister who did not smoke. While both twins had about 30 smaller low-grade adenomas, the twin sister who smoked also had three larger (6-10 mm) adenomas and one focal high-grade adenoma of 70 mm .

Source: GeneReviews — "MUTYH Polyposis"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "MUTYH Polyposis"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with MUTYH Polyposis

Source: GeneReviews — "MUTYH Polyposis"