American Board of Internal Medicine (ABIM) Certification Practice Exam

How is Lynch syndrome inherited?

1. Autosomal recessive

2. Autosomal dominant

3. X-linked

4. Mitochondrial inheritance

The correct answer is: Autosomal dominant

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is primarily inherited in an autosomal dominant manner. This means that only one copy of the mutated gene inherited from an affected parent is sufficient to increase the risk of developing certain types of cancer. In families with Lynch syndrome, individuals have a significantly elevated risk for colorectal cancer and other malignancies, particularly endometrial cancer, as well as a few other cancers. The underlying genetic mutations that cause Lynch syndrome typically affect the DNA mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, and PMS2. When a mutation occurs in one of these genes, the body's ability to fix errors that occur during DNA replication is impaired, leading to an increased likelihood of developing tumors over a person's lifetime. Because the condition can be passed on from one generation to the next with just one affected parent, it exemplifies the inheritance patterns consistent with autosomal dominant conditions. In contrast, autosomal recessive conditions require both copies of a gene to be mutated for an individual to be affected, X-linked conditions are linked to the X chromosome and have different implications for inheritance in males and females, and mitochondrial inheritance involves genes found in