# Constitutional mismatch repair deficiency (CMMRD)

Source: https://onco.cc/terms/constitutional-mismatch-repair-deficiency/  
OnCo record `constitutional-mismatch-repair-deficiency` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

## Fields

- Kind: Term
- Last checked: 2026-11-04
- Also known as: CMMRD; constitutional mismatch repair deficiency syndrome; biallelic mismatch repair deficiency; BMMRD; mismatch repair cancer syndrome; Turcot syndrome
- Tags: gap-fill; hereditary

## Notes

- Orphanet ORPHA:252202. The AACR 2024 update groups CMMRD with Lynch syndrome and polymerase proofreading-associated polyposis as replication repair deficiency syndromes.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Mismatch_repair_cancer_syndrome
- Colas, Eur J Hum Genet 2024: ERN GENTURIS guidelines on constitutional mismatch repair deficiency: https://doi.org/10.1038/s41431-024-01708-6
- Das, Clin Cancer Res 2024: DNA replication repair deficiency syndromes in children and young adults (AACR update): https://doi.org/10.1158/1078-0432.ccr-23-3994
- Orphanet ORPHA:252202: https://www.orpha.net/en/disease/detail/252202

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- technologies: [Capsule endoscopy (PillCam, EndoCapsule, CapsoCam)](https://onco.cc/technologies/capsule-endoscopy-systems/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Whole-body MRI](https://onco.cc/technologies/whole-body-mri/)
- targets: [MLH1](https://onco.cc/targets/mlh1/), [MSH2](https://onco.cc/targets/msh2/), [MSH6](https://onco.cc/targets/msh6/), [PMS2](https://onco.cc/targets/pms2/)
- terms: [Colonoscopy](https://onco.cc/terms/colonoscopy/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Inherited susceptibility to acute lymphoblastic leukaemia (PAX5, ETV6, IKZF1)](https://onco.cc/terms/germline-all-predisposition/), [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)

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