Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and severe inherited condition that significantly increases a child's risk of developing various cancers, particularly in the brain, blood, and digestive system. It is recognized as a distinct childhood cancer predisposition syndrome due to its early onset and broad tumor spectrum.
Understanding Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome
CMMRD syndrome is characterized by a profound genetic vulnerability to cancer. It means that individuals born with this syndrome have a much higher likelihood of developing specific types of cancer at a very young age compared to the general population.
Genetic Basis of CMMRD
The underlying cause of CMMRD syndrome lies in specific genetic mutations. It develops when an individual inherits biallelic germline mutations—meaning mutations in both copies of a gene, inherited from both parents—in one of four crucial genes. These genes are responsible for a vital cellular process known as DNA mismatch repair (MMR). The four genes implicated in CMMRD are:
- MLH1
- MSH2
- MSH6
- PMS2
These MMR genes are essential for correcting errors that occur naturally when DNA is copied during cell division. When these genes are faulty and unable to perform their repair function, DNA errors accumulate throughout the body. This unchecked accumulation of mutations can lead to uncontrolled cell growth, forming tumors and, ultimately, cancer.
Broad Cancer Spectrum
Children affected by CMMRD syndrome are susceptible to a very wide array of tumors. While the overall tumor spectrum is broad, the most commonly observed types of cancers primarily involve:
- Haematological tumors: These include cancers of the blood-forming tissues, such as various forms of leukemia and lymphoma.
- Brain tumors: A significant number of children with CMMRD develop tumors originating in the brain or other parts of the central nervous system.
- Intestinal tract tumors: Cancers affecting the digestive system, particularly the colon and rectum, are also prevalent in individuals with CMMRD.
The aggressive nature and early onset of these cancers necessitate specialized medical attention and surveillance for individuals diagnosed with CMMRD syndrome. Understanding this genetic predisposition is crucial for early detection and targeted management strategies.
For more information on conditions where inherited genetic mutations increase cancer risk, you can learn about Cancer Predisposition Syndromes.
