{"entity":{"id":"constitutional-mismatch-repair-deficiency","kind":"term","name":"Constitutional mismatch repair deficiency (CMMRD)","aka":["CMMRD","constitutional mismatch repair deficiency syndrome","biallelic mismatch repair deficiency","BMMRD","mismatch repair cancer syndrome","Turcot syndrome"],"tldr":"Constitutional mismatch repair deficiency is a rare inherited condition in which a child has two faulty copies of a DNA spell-checking gene, one from each parent, and develops brain, blood and bowel cancers from early childhood. Six-monthly brain scans and early bowel checks find tumours sooner, and these cancers often respond to immunotherapy.","summary":"Caused by biallelic pathogenic variants in MLH1, MSH2, MSH6 or PMS2, the genes that cause Lynch syndrome in a single copy. Confers a very high, lifelong risk of haematological, brain and gastrointestinal cancers; the commonest non-cancer features are café-au-lait macules reminiscent of NF1, other pigmented patches and brain developmental venous anomalies.\n\nThe 2024 ERN GENTURIS guideline (82 recommendations, modified Delphi, 72 experts and a patient representative) sets testing criteria, diagnostic criteria and surveillance: clinical examination every six months; brain MRI every six months in childhood (both prospective cohorts that evaluated earlier protocols support this interval) and annually from age 20; colonoscopy from age 6 with upper endoscopy and capsule endoscopy started at the same time, at intervals of no more than a year, shortening to about six months once polyps are found; whole-body MRI optional. Prospective C4CMMRD and IRRDC cohorts showed a survival benefit for those under surveillance. Temozolomide is no longer recommended; checkpoint immunotherapy should be considered front-line for high-grade glioma and is recommended front-line for large, unresectable or metastatic colorectal tumours.","asOf":"2026-11-04","wikipedia":"https://en.wikipedia.org/wiki/Mismatch_repair_cancer_syndrome","links":[{"label":"Colas, Eur J Hum Genet 2024: ERN GENTURIS guidelines on constitutional mismatch repair deficiency","url":"https://doi.org/10.1038/s41431-024-01708-6"},{"label":"Das, Clin Cancer Res 2024: DNA replication repair deficiency syndromes in children and young adults (AACR update)","url":"https://doi.org/10.1158/1078-0432.ccr-23-3994"},{"label":"Orphanet ORPHA:252202","url":"https://www.orpha.net/en/disease/detail/252202"}],"tags":["gap-fill","hereditary"],"related":[],"cancers":["glioblastoma","colorectal"],"sections":[],"technologies":["whole-body-mri","capsule-endoscopy-systems","germline-testing"],"targets":["mlh1","msh2","msh6","pms2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lynch-syndrome","msi","colonoscopy","hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Orphanet ORPHA:252202. The AACR 2024 update groups CMMRD with Lynch syndrome and polymerase proofreading-associated polyposis as replication repair deficiency syndromes."],"category":"Genomics & genetics"},"route":"/terms/constitutional-mismatch-repair-deficiency/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"technology":[{"id":"capsule-endoscopy-systems","kind":"technology","name":"Capsule endoscopy (PillCam, EndoCapsule, CapsoCam)","route":"/technologies/capsule-endoscopy-systems/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","route":"/technologies/whole-body-mri/"}],"target":[{"id":"mlh1","kind":"target","name":"MLH1","route":"/targets/mlh1/"},{"id":"msh2","kind":"target","name":"MSH2","route":"/targets/msh2/"},{"id":"msh6","kind":"target","name":"MSH6","route":"/targets/msh6/"},{"id":"pms2","kind":"target","name":"PMS2","route":"/targets/pms2/"}],"term":[{"id":"colonoscopy","kind":"term","name":"Colonoscopy","route":"/terms/colonoscopy/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"germline-all-predisposition","kind":"term","name":"Inherited susceptibility to acute lymphoblastic leukaemia (PAX5, ETV6, IKZF1)","route":"/terms/germline-all-predisposition/"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","route":"/terms/lynch-syndrome/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}]}}