Constitutional Mismatch Repair Deficiency, the Most Aggressive Cancer Predisposition Syndrome : Clinical Presentation, Surveillance, and Management
- Author:
Eungu KANG
1
;
Jin Kyung SUH
;
Sang-Dae KIM
Author Information
- Publication Type:Review Article
- From:Journal of Korean Neurosurgical Society 2025;68(3):294-304
- CountryRepublic of Korea
- Language:English
- Abstract: Constitutional mismatch repair deficiency (CMMRD) is a rare and highly aggressive cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair genes. This condition is characterized by early-onset malignancies across multiple organ systems, including central nervous system tumors, hematological cancers, and gastrointestinal malignancies. CMMRD-associated tumors exhibit hypermutation and microsatellite instability, resulting in a high tumor mutation burden and rendering these malignancies responsive to immune checkpoint inhibitors (ICIs). ICIs targeting programmed cell death protein-1 and programmed cell death ligand 1 have demonstrated remarkable efficacy, particularly in hypermutated tumors, providing durable responses and improving survival outcomes. Advances in genetic and molecular diagnostics have enhanced the ability to identify CMMRD early, allowing for the implementation of comprehensive surveillance programs and improved management strategies. A multidisciplinary and individualized approach is essential for managing CMMRD patients. This review underscores the importance of early diagnosis, surveillance, and emerging therapeutic approaches to improve outcomes and quality of life for individuals and families affected by this devastating syndrome.
