The Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome is a rare congenital condition associated with a range of neoplasms that may appear during childhood or adolescence. It shares with Lynch Syndrome a defect in mismatch repair.
Pathogenesis: biallelic germline mutations in one of four mismatch repair genes
Mismatch repair genes affected: MLH1, MSH2, MSH6, PMS2
Inheritance: autosomal recessive, typically affecting offspring of a consanguineous mating
Non-malignant features:
(1) features of neurofibromatosis type 1, especially cafe au lait macules
(2) occasional pediatric SLE
Malignant tumors that may develop include:
(1) malignant lymphoma
(2) ALL
(3) AML
(4) atypical chronic myeloid leukemia
(5) glioblastoma
(6) supratentorial primitive neuroectodermal tumor
(7) medulloblastoma
(8) colorectal cancer
(9) small intestinal adenocarcinoma
(10) endometrial cancer
(11) urothelial carcinoma of the ureter or renal pelvis
(12) neuroblastoma
(13) Wilms tumor
(14) rhabdomyosarcoma
(15) ovarian neuroectodermal tumor
(16) infantile myofibromatosis
(17) breast cancer
(18) sarcoma, NOS
About a third of patients develop 2 or more neoplasms.
