High‐grade brain tumors in siblings with biallelic MSH6 mutations

Biallelic germline mutations of Constitutional mismatch repair‐deficiency syndrome (CMMR‐D) genes, MLH1, MSH2, MSH6, and PMS2 are characterized by increased risk of childhood malignancy. We report a case with CMMR‐D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri and 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 on brain tumors in CMMR‐D families shows that they are treatment‐resistant and lead to early death. Identification of patients with CMMR‐D is critical, and specific cancer screening programs with early surgery are recommended. Pediatr Blood Cancer 2011; 57: 1067–1070. © 2011 Wiley‐Liss, Inc.

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