title: [Constitutional mismatch repair-deficiency syndrome (CMMR-D) - a case report of a family with biallelic MSH6 mutation].
abstract: This work gives comprehensive information about new recessively inherited syndrome characterized by development of childhood malignancies. Behind this new described syndrome, called Constitutional mismatch repair-deficiency syndrome (CMMR-D), there are biallelic mutations in genes, which cause adult cancer syndrom termed Lynch syndrom (Hereditary non-polyposis cancer syndrom-HNPCC) if they are heterozygous mutations. Biallelic germline mutations of genes MLH1, MSH2, MSH6 and PMS2 in CMMR-D are characterized by increased risk of hematological malignancies, atypical brain tumors and early onset of colorectal cancers. An accompanying manifestation of the disease are skin spots with diffuse margins and irregular pigmentation reminiscent of Café au lait spots of NF1. This paper reports a case of a family with CMMR-D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri, T-ALL in an 11-year-old female and glioblastoma multiforme in her 10-year-old brother, both with rapid progression of the diseases. A literature review of brain tumors in CMMR-D families shows that they are treatment-resistant and lead to early death. Therefore, this work highlights the importance of early identification of patients with CMMR-D syndrome - in terms of initiation of a screening program for early detection of malignancies as well as early surgical intervention.
authors.affiliation: II. detská klinika, LF UK a DFNsP Bratislava, Slovenská republika. denisa.ilencikova@dfnsp.sk
authors.forename: D
authors.initials: D
authors.lastname: Ilenčíková
mesh_terms: D000483:Alleles; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D019080:Cafe-au-Lait Spots / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein