Germline mismatch repair gene mutations in children with tumors: a case series from two centers.

Background: Mismatch repair (MMR) deficiency can lead to constitutional mismatch repair deficiency (CMMRD) syndrome and Lynch syndrome (LS). These two genetic disorders are associated with a broad spectrum of tumor types, including a variety of brain tumors. Usually, tumors associated with LS are more common in adults and rarely occur in children. The characterizations of café-au-lait macules (CALMs) are relatively similar in CMMRD syndrome and neurofibromatosis type 1 ( Case Description: We identified five patients with MMR gene germline mutations and tumors from the University of Hong Kong - Shenzhen Hospital (four cases) and Hong Kong Children's Hospital (one case) within a 2-year period (June 2021 to June 2023). The clinical features of these patients were reviewed and compared with those detailed in the literature. Of the four patients with CMMRD syndrome, two had medulloblastomas, one had low-grade glioma, and one had desmoid fibromatosis. The only LS patient was diagnosed with medulloblastoma at the age of 10. In terms of the gene mutations of the CMMRD syndrome patients, two had the Conclusions: More than half of CMMRD syndrome and LS patients have no family history of cancer; thus, the absence of a positive family history does not rule out CMMRD syndrome and LS. A better diagnostic approach is to perform genetic testing to rule out the risk as early as possible when a newborn presents with cafe-au-lait spots, which are a typical feature of hereditary syndromes. Therefore, it is important to use germline genetic testing, combined with clinical phenotypic observation, to establish a diagnosis of a cancer susceptibility syndrome caused by an MMR gene mutation.