Lynch syndrome associated with a MLH1 gene mutation: preventive and personalized monitoring based on the results of molecular testing
We report a family case of hereditary non-polyposis colorectal cancer with an autosomal dominant inheritance pattern known as Lynch syndrome. The development of Lynch syndrome is associated with mutations in the genes MLH1, MSH2, MSH6, PMS2, and EPCAM. Patients with this disorder have an increased risk of various cancers. The proband was a 36-year-old male with non-polyposis sigmoid colon cancer and had a family history of colon cancer in 4 generations. Using next generation sequencing (NGS), we identified the c.298C>T mutation (p.Arg100Ter) in the exon 3 of the MLH1 gene, described as a cause of Lynch syndrome in international genomic databases. This confirmed the diagnosis of Lynch syndrome. Clinical manifestation of the disease was observed in 4 generations of the proband’s family. All relatives available for examination were tested for this mutation. Eight out of 13 people of the fifth generation were found to be carriers of this mutation, which allows to make the diagnosis of Lynch syndrome before the development of clinical symptoms. Three out of 4 children of the patient had this mutation. Three out of 4 children of the proband’s brother, who had this mutation and developed cancer at the age of 27 years old, also inherited this mutation. The 30-year-old proband’s sister was timely diagnosed with Lynch syndrome before the disease manifestation. The mean age at the diagnosis of colorectal cancer associated with the Arg100Ter mutation in the MLH1 gene in this family was 37 years. Diagnosis of Lynch syndrome in this family allowed the identification of proband’s relatives at high risk of cancer development. All carriers of the MLH1 gene mutation were recommended to follow the prophylactic program of cancer development monitoring according to the National Comprehensive Cancer Network (NCCN) protocol.