Constitutional Mismatch Repair Deficiency (CMMRD) (aka Biallelic Mismatch Repair Deficiency or Homozygous Mismatch Repair Mutations) is a hereditary cancer predisposition that typically presents in infancy, childhood or young adulthood. Individuals with CMMRD are at risk for developing hematologic malignancies, brain tumors, colon, small bowel, uterine, gastric, urologic and other types of cancer. Individuals with CMMRD have an estimated a 16-fold increased risk for persons with biallelic MSH2 mutations. They can have multiple diagnoses of these cancers throughout their life. Additionally, café au lait macules have been reported in these individuals.
CMMRD is caused by mutations in the Mismatch Repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. When a person has one mutation in one of their MMR gene then they have Lynch syndrome. A person must have 2 gene mutations in the same MMR gene to develop CMMRD. For example, if both their mother and father had one mutation in their PMS2 genes they would have to inherit both their mother’s and father’s mutated copy. Couples who each carry a single gene mutation in the same MMR gene have a 1 in 4 or 25% risk to have a child with CMMRD. We recommend couples who each carry a MMR gene mutation in the same MMR gene see a genetic counselor who specializes in prenatal genetics either during or prior to pregnancy to discuss available testing options and to learn more about this condition.
Recently, a new European consortium was established with the aim of improving care for patients with CMMRD. On February, 2014 this group of Lynch syndrome and CMMRD experts published screening guidelines for individuals with CMMRD. To review the paper please click: CMMRD Screening Guidelines 2014.
Below is a table of the recommended screening guidelines for those with CMMRD.