Constitutional mismatch repair deficiency syndrome

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare disorder that greatly increases the risk of developing different types of cancer throughout a person's lifetime. Affected individuals often develop their first cancer in childhood. The cancers that most commonly occur in people with CMMRD are cancers of the colon and rectum (collectively referred to as colorectal cancer), blood (leukemia or lymphoma), and brain.

Approximately 50 percent of people with CMMRD will develop cancer by age 10, and 90 percent will develop cancer by age 18. Brain cancers, leukemias, and lymphomas tend to occur at a younger age than colorectal cancer in affected individuals. Nearly all people with CMMRD will develop a second cancer if they survive the first cancer. 

People with CMMRD often develop multiple abnormal growths (polyps) on the lining of the colon. If these polyps are not removed, they may become cancerous over time. 

Brain cancers in people with CMMRD are often high-grade gliomas or glioblastomas, which are tumors that are made up of cells called glial cells. 

The most common blood cancers in people with CMMRD are non-Hodgkin lymphomas, such as lymphoblastic lymphoma. These cancers primarily affect white blood cells known as T cells. 

Other cancers that can occur in people who have CMMRD include cancers of the small intestine, urinary tract, or lining of the uterus. Cancers of the connective tissue and bone (sarcomas) may also develop. 

Some affected individuals have patches of skin that are unusually light in color (hypopigmented). Many people with CMMRD develop features similar to those seen in people with a condition called neurofibromatosis type 1. These features include changes in skin coloring (pigmentation), which are characterized by multiple flat patches on the skin that are darker than the surrounding area (café-au-lait spots). Because of these shared features, CMMRD is sometimes initially misdiagnosed as neurofibromatosis type 1. 

Many people with CMMRD also develop a noncancerous (benign) feature called developmental venous anomaly, which is a rearrangement of the small veins in the brain. This feature can only be seen with medical imaging.

Due to the young age at which people with CMMRD develop cancer, the lifespan of affected individuals is typically shortened, with many people surviving only into adolescence or early adulthood.