title: Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.
abstract: Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer and a range of other cancer types. However, surveillance for cancers other than colorectal cancer is still of uncertain value. Prophylactic surgery, especially for the uterus and its adnexa is an option in female mutation carriers. Chemoprevention of colorectal cancer with aspirin is actively being investigated in this syndrome and shows promising results. In contrast, the Constitutional Mismatch Repair Deficiency syndrome is rare, features a wide spectrum of childhood onset cancers, many of which are brain tumors with high mortality rates. Future studies are very much needed to improve the care for patients with this severe disorder.
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30001, 9700RB, Groningen, The Netherlands. Electronic address: r.h.sijmons@umcg.nl.
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000CA Rotterdam, The Netherlands. Electronic address: r.hofstra@erasmusmc.nl.
authors.forename: Robert M W
authors.initials: RMW
authors.lastname: Hofstra
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis; D053843:DNA Mismatch Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics*
keywords: Constitutional Mismatch Repair Deficiency syndrome; DNA Mismatch repair; Lynch syndrome; MLH1; MSH2; MSH6; PMS2; clinic; review