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Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1
Author(s) -
Wimmer K.,
Rosenbaum T.,
Messiaen L.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12904
Subject(s) - medicine , rhabdomyosarcoma , neurofibromatosis , dna mismatch repair , childhood cancer , germline , cancer , genetics , sarcoma , biology , gene , pathology , colorectal cancer
Constitutional mismatch repair ( MMR ) deficiency ( CMMRD ) is a rare childhood cancer susceptibility syndrome resulting from biallelic germline loss‐of‐function mutations in one of the MMR genes. Individuals with CMMRD have high risk to develop a broad spectrum of malignancies and frequently display features reminiscent of neurofibromatosis type 1 ( NF1 ). Evaluation of the clinical findings of genetically proven CMMRD patients shows that not only multiple café‐au‐lait macules but also any of the diagnostic features of NF1 may be present in a CMMRD patient. This phenotypic overlap may lead to misdiagnosis of CMMRD patients as having NF1 , which impedes adequate management of the patients and their families. The spectrum of CMMRD ‐associated childhood malignancies includes high‐grade glioma, acute myeloid leukaemia or rhabdomyosarcoma, also reported as associated with NF1 . Reported associations between NF1 and these malignancies are to a large extent based on studies that neither proved the presence of an NF1 germline mutation nor ruled‐out CMMRD in the affected. Hence, these associations are challenged by our current knowledge of the phenotypic overlap between NF1 and CMMRD and should be re‐evaluated in future studies. Recent advances in the diagnostics of CMMRD should render it possible to definitely state or refute this diagnosis in these individuals.