Hereditary Cancer and Genetic Testing

Other medical concerns for people with inherited MLH1 mutations

Some mutations in the MLH1 gene cause a subset of Lynch syndrome that is sometimes referred to as Muir-Torre syndrome. In addition to increased risk of Lynch syndrome cancers, people with Muir-Torre syndrome also have increased risk of developing uncommon skin tumors. These rare skin tumors include sebaceous adenomas and carcinomas, which occur in glands that produce an oily substance called sebum (sebaceous glands). Multiple rapidly growing tumors called keratoacanthomas may also occur, usually on sun-exposed areas of skin. Annual skin examination by a dermatologist is recommended for all individuals with inherited MLH1 mutations, whether or not they or a family member have a known history of these skin tumors.

Children who inherit an MLH1 mutation from both their mother and their father can have a rare syndrome known as “constitutional mismatch repair deficiency (CMMRD).” CMMRD can cause high risks of various cancers in childhood and young adulthood. Children with CMMRD syndrome may have blood (hematological) and brain/central nervous system tumors and colorectal and other cancers that are typically seen in Lynch syndrome patients at a later age. Many, but not all CMMRD patients show features that resemble neurofibromatosis, a genetic disorder that causes tumors to form on nerve tissue, particularly harmless, light brown “café au lait” spots on the skin. Both parents must have an MLH1 mutation for a child to have CMMRD. Couples where one partner has a known MLH1 mutation may wish to speak with a genetic counselor about testing the other partner prior to having children.

There are options using assisted reproduction technology and preimplantation genetic diagnosis for parents to select embryos that are free of inherited MLH1 mutations.