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. The gene discussed is FGFR1; the disease is neoplasm.