Frequency
CMMRD syndrome is a rare disorder; more than 200 affected individuals have been reported in the scientific literature.
Causes
Mutations in the PMS2 gene are the most common cause of CMMRD syndrome, and mutations in the MLH1, MSH2, or MSH6 gene cause the remaining cases. These four genes are involved in repairing errors that occur when DNA is copied in preparation for cell division (a process called DNA replication). Because these genes work together to fix DNA errors, they are known as DNA mismatch repair (MMR) genes.
Mutations in any of these genes result in near or complete loss of functional protein. A shortage of one of these proteins eliminates mismatch repair activity and prevents the proper repair of errors that occur during DNA replication. The errors accumulate and disrupt other genes involved in important cellular processes such as controlling cell growth and division (proliferation). Uncontrolled cell growth can lead to childhood cancer in people with CMMRD syndrome.
It is thought that the features of neurofibromatosis type 1 in people with CMMRD syndrome are due to genetic changes in the NF1 gene that result from a loss of mismatch repair. These changes are present only in certain cells (somatic mutations), whereas NF1 gene mutations that are present in all cells of the body cause neurofibromatosis type 1.
Inheritance
CMMRD syndrome is inherited in an autosomal recessive pattern, which means having mutations in both copies of the gene greatly increases the risk of developing cancer. The parents of an individual with CMMRD syndrome each carry one copy of the mutated gene.
A single mutation in any of the genes associated with CMMRD syndrome generally leads to a different cancer predisposition syndrome called Lynch syndrome. Because the parents of an individual with CMMRD syndrome typically have a single copy of the mutated gene, they may have Lynch syndrome. Lynch syndrome increases the risk of many types of cancer, particularly colorectal cancer, but also cancers of the stomach, small intestine, gallbladder ducts, upper urinary tract, endometrium, brain, and skin. Unlike CMMRD syndrome, individuals with Lynch syndrome often develop these cancers in adulthood. Additionally, not all people with Lynch syndrome develop cancerous tumors, so a person with CMMRD syndrome might not have a history of cancer in their family.
Other Names for This Condition
- Biallelic mismatch repair deficiency syndrome
- BMMRD
- Mismatch repair cancer syndrome
- Mismatch repair deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Durno C, Boland CR, Cohen S, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Levin TR, Lieberman D, Robertson DJ, Rex DK. Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency (BMMRD) Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2017 May;152(6):1605-1614. doi: 10.1053/j.gastro.2017.02.011. Epub 2017 Mar 28. Citation on PubMed
- Lavoine N, Colas C, Muleris M, Bodo S, Duval A, Entz-Werle N, Coulet F, Cabaret O, Andreiuolo F, Charpy C, Sebille G, Wang Q, Lejeune S, Buisine MP, Leroux D, Couillault G, Leverger G, Fricker JP, Guimbaud R, Mathieu-Dramard M, Jedraszak G, Cohen-Hagenauer O, Guerrini-Rousseau L, Bourdeaut F, Grill J, Caron O, Baert-Dusermont S, Tinat J, Bougeard G, Frebourg T, Brugieres L. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort. J Med Genet. 2015 Nov;52(11):770-8. doi: 10.1136/jmedgenet-2015-103299. Epub 2015 Aug 28. Citation on PubMed
- Sijmons RH, Hofstra RMW. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations. DNA Repair (Amst). 2016 Feb;38:155-162. doi: 10.1016/j.dnarep.2015.11.018. Epub 2015 Dec 11. Citation on PubMed
- Wimmer K, Kratz CP, Vasen HF, Caron O, Colas C, Entz-Werle N, Gerdes AM, Goldberg Y, Ilencikova D, Muleris M, Duval A, Lavoine N, Ruiz-Ponte C, Slavc I, Burkhardt B, Brugieres L; EU-Consortium Care for CMMRD (C4CMMRD). Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD). J Med Genet. 2014 Jun;51(6):355-65. doi: 10.1136/jmedgenet-2014-102284. Epub 2014 Apr 15. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.