Constitutional Mismatch Repair Deficiency Syndrome as a Cause of Numerous Malignancies in a Teenage Patient—A Case Report

Abstract

Constitutional mismatch repair deficiency syndrome is a genetic disorder resulting from a biallelic mutation in one of the following genes: MLH1, MSH2, MSH6, or PMS2. Individuals with constitutional mismatch repair deficiency are highly predisposed to develop both hematological and solid cancers in childhood, particularly lymphoma, brain tumors, and gastrointestinal neoplasms. We report a case of a boy diagnosed with B-cell acute lymphoblastic leukemia at the age of 3. In 2013, at the age of 6, head magnetic resonance imaging revealed hamartoma and astrocytoma lesions in the central nervous system. Two years after treatment completion, a diagnosis of precursor T-cell lymphoblastic lymphoma, accompanied by the vena cava syndrome, was established and treated accordingly. During treatment, a genetic test using Sanger sequencing was performed—a biallelic mutation in the MSH6 gene was detected. The study revealed that the mutation 17-bp c.2277-2293del. was inherited from the patient’s mother. The second mutation, 5-bp c.1135_1139delAGAGA, developed inpatient de novo. At the age of 14, the diagnosis of isolated bone marrow relapse of acute lymphoblastic leukemia B-cell type was established. Due to the almost exceeded total dose of anthracyclines, the patient’s treatment included blinatumomab, and subsequently, he was qualified for allogeneic hematopoietic cell transplantation. The patient remains in complete remission for 11 months after allogeneic hematopoietic stem cell transplantation under the care of the transplant center.