Pathogenic variants (disease-causing) in both copies of the MBD4 gene cause MBD4-Associated Neoplasia Syndrome (MANS). MANS is a rare inherited condition linked to high rates of colorectal polyps (sometimes hundreds), early-onset colorectal cancer, and an elevated risk of blood cancers (like acute leukemia) and other tumors such as uveal (eye) melanoma. The exact lifetime risks of MBD4-related syndrome is unknown due to its rarity. Management of MBD4–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. MBD4 variants are not known to be more common in the Ashkenazi Jewish population.
As noted above, MANS exhibits autosomal recessive inheritance. This means that both parents must be carriers of an MBD4 pathogenic variant to have a 25% chance to have a child with the condition; a carrier means that an individual has a single MBD4 pathogenic variant. Carriers, to the best of our knowledge, do not have an increased of cancer or polyps. If an individual has MANS, the chance their children could have it depends on the genetic make-up of the other parent.
Resources:
Written December 2025
