The specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway were identified, including v-raf murine sarcoma viral oncogene homolog B1 (BRAF) (V600E), Mitogen-Activated Protein Kinase Kinase 1 (MAP2K1), neuroblastoma RAS viral oncogene homolog (NRAS), and Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), which indicated that the MAPK/ERK pathway may play a key role in the pathomechanism of LCH, Erdheim–Chester disease (ECD), and even other non-LCH diseases [20,21,22,23,24,25,26,27,28]. Here, MAP2K1 is linked to familial atrioventricular septal defect.