HGG 2. Brain tumors in children with DNA mismatch repair deficiency syndrome

Document Type

Conference Paper


Emergency Medicine


DNA mismatch repair (MMR) deficiency syndrome, also referred to as the recessive form of Turcot syndrome, is characterized by childhood onset of CNS tumors, hematologic malignancies, colorectal cancers, and NF1-like cutaneous lesions. Multiple brain tumors have been associated with MMR including medulloblastoma, glioblastoma multiforme (GBM), astrocytoma, oligodendroglioma, and SPNET. Both homozygous and compound heterozygous mutations in the MLH1, MSH2, PMS2, and MSH6 genes have been reported. We describe three families with the clinical diagnosis of MMR deficiency syndrome from one institution. Family 1 is a nonconsanguineous Pakistani family with two children with cafe-au-lait spots (CALS). The son was diagnosed with lymphoma at age 5 and colorectal cancer at age 8, while the daughter was diagnosed with GBM at age 8, related to being homozygous for a nonsense mutation in MSH6. Family 2 is a consanguineous Indian family with a 6-year-old male with CALS and synchronous diagnosis of multifocal GBM and T-cell lymphoblastic lymphoma. This child is homozygous for an intragenic PMS2 deletion. Family 3 is a Mexican/Guatemalan nonconsanguineous family with two children with multiple CALS. The older sibling was diagnosed with T-cell lymphoblastic lymphoma at age 5 years and GBM at age 6 years. A younger sibling, who is now 5 years old, was recently diagnosed with a GBM, and mutation analysis is underway. In all three families there was no evidence for hereditary nonpolyposis colon cancer–associated cancers in obligate heterozygous mutation carriers. This group of patients supports careful skin exams for NF1-associated lesions in newly diagnosed patients with pediatric brain tumors and diagnostic consideration of MMR deficiency syndrome in addition to NF1. Family members and patients with MMR deficiency syndrome are at increased risk for lymphoma and also require screening by colonoscopy for colon cancer risk. Screening guidelines for patients with DNA MMR deficiency, which should include routine colonoscopy, need to be developed.


This work was published before the author joined Aga Khan University.

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