What is CMMRD?

Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome is a rare condition that makes a child more likely to develop:

  • Brain cancer
  • Cancers in blood and lymph systems
  • Polyps (abnormal growths in the intestinal tract) and cancers in the gastrointestinal tract
  • Cancers in the female reproductive organs (for example, the uterus and ovaries)
  • Certain skin issues, for example café au lait spots (flat brown colored areas on the skin) or patches of skin that are lighter than the overall skin tone
  • Other rare pediatric cancers

A child with CCMRD Syndrome can develop more than one type of cancer at a time or more than one cancer during their lifetime.

CCMRD Syndrome is related to changes in the genes MLH1, MSH2, MSH6, or PMS2 and rarely in a gene called EPCAM. Genes carry information telling cells in the body how to work. The MLH1, MSH2, MSH6 and PMS2 genes help to fix a specific type of DNA damage through a process called “mismatch repair” or MMR. It is harder for people with CCMRD Syndrome to fix the damage that naturally occurs in their genes. This can lead to the growth of polyps and cancer at an early age.

Most people have two working copies of each of the MMR genes in their cells. One copy is inherited from each parent. A change in the gene that causes it to not work right is called a variant. When someone inherits an MMR gene variant from each parent, they have CCMRD Syndrome. In other words, this person has a variant affecting each of the 2 copies of an MMR gene.

Most children with CCMRD Syndrome inherit the MMR gene variants from their parents. Parents of a child with CCMRD Syndrome have a 25% (or 1 in 4) chance for each pregnancy of having a child with the same syndrome.

All children of a person with CCMRD Syndrome will inherit one MMR variant. To understand the chances of having a child with this syndrome, the partner of a person with the syndrome might want to consider genetic testing to see if he or she also carries an MMR gene variant.

If a person has one working copy and one non-working copy of an MMR gene, they have a condition known as hereditary non-polyposis colorectal cancer, or Lynch Syndrome. Generally, when a child has CMMRD, both parents are assumed to have Lynch Syndrome.

People with Lynch Syndrome are more likely to develop colon polyps and certain types of cancer, such as colon, uterine, ovarian, and small bowel cancer, most commonly as adults. A person with Lynch Syndrome will need to be followed closely by a health care provider (a gastroenterologist who knows the condition well is best).

A doctor may suspect this diagnosis after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.

Diagnosing this syndrome is usually done by sequencing the MMR genes to find variants (changes in the genes). Both copies of the person’s MMR genes are checked for possible changes.

In some cases, tests may be performed on a sample of a person’s cancer to better direct genetic testing.

For people with this syndrome, the exact risk of developing cancer during their lifetime is not known at this time, but it is thought to be very high. Because CMMRD Syndrome can cause a wide variety of cancers, it is hard to predict what type of cancer a child with this condition may develop and when that cancer will occur.

Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.

A person with Lynch Syndrome will need to be followed closely by a health care provider (a gastroenterologist who knows the condition well is best). There are well-established cancer screening guidelines for Lynch Syndrome. Starting in adulthood, regular screening exams, known as colonoscopies, are recommended to look for and remove any polyps and to detect colon cancer if it is present. Adult women with Lynch Syndrome can also consider screening of the reproductive organs.

Other ideas to reduce the risk of cancer include:

  • Eat a healthful diet with lots of fruits and vegetables
  • Get regular exercise
  • Avoid smoking or using tobacco products
  • Avoid secondhand smoke
  • Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
  • Get medical attention for unusual or ongoing symptoms

Because of the other medical concerns related to this syndrome, specialists in the following area may need to assess a child with CMMRD:

  • Dermatology

Resources about colon cancer and MMR genes:

Other resources:

Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program