What is Constitutional Mismatch Repair Deficiency Syndrome?

Constitutional mismatch repair deficiency (CMMRD) syndrome is a genetic condition in which individuals are born with a predisposition to develop many different types of childhood and adult-onset cancers. The average age of cancer diagnosis in patients with this syndrome is age 7.

Cancers most often diagnosed in children with CMMRD include:

  • Leukemia and lymphoma (especially non-Hodgkin lymphoma)
  • Glioblastoma multiforme and high-grade gliomas
  • Colon cancer

What are the causes?

CMMRD syndrome is caused by genetic changes in both copies of a mismatch repair gene. These include MLH1, MSH2, MSH6, PMS2 and EPCAM. An individual must inherit a nonworking copy of a gene from each of their parents in order to be affected by this syndrome. In most cases, the parents themselves will not be diagnosed with cancer and the child with cancer is most often the first patient identified in the family. Each parent of a child with CMMRD has an adult-onset syndrome called Lynch Syndrome, which increases lifetime risks for colon, endometrial, and other types of cancers.

The incidence of CMMRD syndrome is unknown and thought to be very rare. Fewer than 500 patients with it have been reported in the medical literature.

How is constitutional mismatch repair deficiency syndrome diagnosed?

CMMRD syndrome can be diagnosed through genetic testing that is facilitated by a genetic counselor or genetics services provider.

Treatment and monitoring

Guidelines exist for the medical monitoring of children and adults with CMMRD syndromes. These patients should receive their care at centers with expertise in this syndrome.