Constitutional Mismatch Repair Deficiency Syndrome
Synonym: CMMR-D, Mismatch Repair Cancer syndrome, MMRCS, Childhood Cancer Syndrome, CCS, Biallelic Mismatch Repair Gene Mutations Associated Early Onset Cancer, Lynch syndrome type III
Mode of Inheritance: AR
OMIM number: 276300
PMS2, mapped to 7p22
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
leukemia, chronic myeloid (CML)
primitive neuroectodermal tumor (PNET)
small intestinal cancer
Tumor Features (possible)
ovarian sarcoma (incl. pPNET of ovary)
Wilms' tumor (nephroblastoma)
café au lait spots
iris, Lisch nodules
Non-tumor Features (possible)
corpus callosum agenesis
gray matter heterotopia of the brain
Multiple café au lait spots, axillary freckling, Lisch nodules of the iris and occasionally simple or plexiform neurofibromas and tibia dysplasia, all features also observed in NF1, and early onset of cancer are typical for this syndrome. Reported tumors include colorectal cancer, small intestinal cancer, oligopolyposis, leukemia (ALL, AML, AL not further specified, CML), non-Hodgkin lymphoma, brain tumors (glioblastoma, astrocytoma, oligodendroglioma medulloblastoma, supratentorial primitive neuroectodermal tumors (SPNET)), Wilms' tumor, ovarian neuroectodermal tumor, neuroblastoma, rhabdomyosarcoma and endometrial cancer. IgA deficiency has been observed as well. In a few patients with CMMR-D, agenesis of the corpus callosum and gray matter heterotopia have been observed.
The syndrome is caused by biallelic mutations of the DNA Mismatch Repair (MMR) Genes MLH1, MSH2, MSH6 or PMS2.[1-12,17 reviewed in 13,14].
There is clinical overlap with Lynch syndrome, associated with single inherited MMR gene mutations. Lynch syndrome type III has therefore been coined as the name for the bi-allelic MMR gene mutation disorder. Turcot syndromefeatures brain tumors & colorectal polyps; a subset of cases have in fact Constitutional Mismatch Repair Deficiency Syndrome.