A Novel KDR Mutation in an Infant With a Non-Involuting Congenital Hemangioma

Congenital hemangioma (CH) is a rare, benign vascular tumor present at birth and molecularly characterized by somatic mutations in angiogenic signaling pathways, most commonly activating mutations in GNA11 and GNAQ, although additional genetic drivers remain incompletely defined. Genomic sequencing of lesional tissue from a child with a non-involuting congenital hemangioma (NICH) identified a likely pathogenic mutation in the kinase insert domain receptor (KDR) gene. KDR encodes vascular endothelial growth factor (VEGF) receptor 2, a central regulator of endothelial proliferation and angiogenesis. This previously unreported variant in CH implicates receptor tyrosine kinase-mediated VEGF signaling as a distinct pathogenic mechanism and expands the molecular spectrum of CH, suggesting a biologically distinct subset of tumors lacking canonical GNA11/GNAQ mutations.