MLH1 Gene Mutations (Lynch Syndrome)

MLH1 is a gene that helps repair damage to your DNA. Inherited mutations in the MLH1 gene cause Lynch syndrome. People with Lynch syndrome have an increased risk for several types of cancer. Other names for Lynch syndrome include:

• Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
• Muir-Torre syndrome, which refers to a subset of Lynch syndrome in which people have an increased risk of developing rare skin tumors.

People with an inherited MLH1 mutation have an increased risk for many cancers, especially of the large intestine (the colon and the rectum) and uterus (endometrium). Expert guidelines include estimates of the lifetime cancer risks for people with MLH1 mutations.

Although the lifetime risk for cancer with an MLH1 mutation is very high, not everyone with the mutation develops cancer. Following the guidelines for screening and prevention increases the chances of preventing cancer or catching it at its earliest and most treatable stage.

MLH1 mutations are passed down from parents to children, but they do not skip generations. Each person with an MLH1 mutation has a 50% chance of passing their mutation on to each of their children. Children who did not inherit their parent's MLH1 mutation cannot pass the mutation to their children. 

People with an MLH1 mutation who never develop cancer can still pass their mutation on to their children. A child who inherits their parent's MLH1 mutation will be at increased risk for cancer. 

People with an MLH1 mutation have options for screening, prevention and treatment of hereditary cancer. There are expert guidelines and clinical trials that focus on:

• screening and early detection
• risk-reduction
• treatment 

These expert guidelines are updated every year based on new research. 

There may be other medical concerns, including a rare childhood disease known as “constitutional mismatch repair deficiency (CMMRD),” which can happen in people who inherit a mutation in both copies of their MLH1 gene.  

If you test positive for an MLH1 mutation, you should inform your close blood relatives (first-, second-, and third-degree relatives) about your test results and encourage them to speak with a genetics expert.