About 90% of cases belong to one of 5 groups with mutations in either PTPN11, NRAS, KRAS, CBL, or NF1. The first three subtypes (PTPN11, NRAS, KRAS) are characterized by heterozygous somatic gain-of-function mutations in non-syndromic children, while JMML in neurofibromatosis type 1 and JMML in children with CBL-syndrome are characterized by germ line RAS disease and acquired biallelic inactivation of the NF1 or CBL gene in hematopoietic cells (12, 37). The gene discussed is CBL; the disease is neurofibromatosis type 1.