Mismatch repair cancer syndrome

Genetics

Under the name constitutional mismatch repair-deficiency (CMMR-D), it has been mapped to MLH1, MSH2, MSH6 or PMS2. Monoallelic mutations of these genes are observed in the condition known as Lynch syndrome or hereditary nonpolyposis colorectal cancer, while biallelic mutations are observed in CMMR-D. People expressing the HNPCC (which itself is considered autosomal dominant) trait are considered carriers of CMMR-D, thus CMMR-D is classified as autosomal recessive.

The term "childhood cancer syndrome" has also been proposed. Café-au-lait macules have been observed.

Diagnosis

Childhood to early adult onset HNPCC + malignant gliomas. The polyps developed tend to be larger, fewer, and progress to malignancy earlier than those seen in familial adenomatous polyposis, a clinically similar condition with different underlying mutations. Diagnostic testing consists of a blood sample being collected, and a genetic specialist compares two copies of a patient's gene to normal MMR genes. If there are differences in the genes, the specialists are able to further test and decide if the patient has the deficiency.

History

OMIM currently includes "Turcot syndrome" under Mismatch repair cancer syndrome. Turcot syndrome is the association between familial polyposis of the colon and brain tumors like medulloblastoma, malignant glioma. It was first reported by Canadian surgeon Jacques Turcot (1914-1977 ) et al. in 1959 and hence carries the first author's name.

References

References

1. {{OMIM. 276300
2. (June 2009). "Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome". Journal of Medical Genetics.
3. (September 2008). "Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg?". Human Genetics.
4. (January 2008). "Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1". European Journal of Human Genetics.
5. (March 2008). "Biallelic PMS2 mutations and a distinctive childhood cancer syndrome". Journal of Pediatric Hematology/Oncology.
6. (June 2008). "Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2". Pediatric Blood & Cancer.
7. "Constitutional Mismatch Repair Deficiency Syndrome".
8. {{DorlandsDict. eight/000112462. Turcot syndrome
9. (1959). "Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases". Diseases of the Colon and Rectum.