Clinical challenges of cancer predisposition syndromes with pediatric central nervous system tumors: a single-center...

Recent developments in genetic testing have demonstrated that cancer predisposition syndrome (CPS) is present in approximately 15% of pediatric central nervous system (CNS) tumors; however, the optimal eligibility and timing of germline genetic testing in these patients have not been determined yet.

We retrospectively examined the clinical and genetic characteristics of pediatric CNS tumor patients diagnosed with CPS at Saitama Children's Medical Center between December 2016 and December 2022.

Among approximately 83 pediatric CNS tumor patients at our institution, 12 (14.5%) were diagnosed with CPS. Only 2 patients had a family history of cancer. A total of 6 patients were identified with CPS before developing a tumor, including 4 with neurofibromatosis type 1, one with 22q11.2 deletion syndrome, and one with von Hippel-Lindau disease. The remaining 6 patients were identified as having CPS only after the development of tumors in 2 with Li-Fraumeni syndrome, one with familial adenomatous polyposis, one with Cowden disease, one with rhabdoid tumor predisposition syndrome, and one with Gorlin syndrome. Cancer gene panel testing discovered germline mutations in 4 patients. Notably, one patient with a lateral ventricle tumor was provisionally diagnosed with choroid plexus carcinoma following the finding of a TP53 germline mutation by liquid biopsy. Another patient with 22q11.2 deletion syndrome developed pineoblastoma, with confirmed biallelic inactivation of DGCR8.

A subset of CPS in pediatric CNS tumors was challenging to diagnose before tumor development. These findings highlight the need for refined genetic screening criteria to enhance CPS diagnosis and management.