Genetically, <i>ACVR1</i> mutations were more common whereas <i>MGMT</i> methylation, <i>FGFR1</i>, and <i>NF1</i> mutations were less prevalent in the pediatric cohort.<h4>Conclusion</h4>Pediatric <i>H3</i>K27M-mutant midline gliomas were demographically, clinically, and molecularly distinct from adult patients, highlighting an opportunity to refine the risk stratification for these neoplasms. This evidence concerns the gene ACVR1 and neoplasm.