A. NF1 patients are predisposed to developing symptoms affecting multiple cells of origin and tissues. Some manifestations associated with NF1, such as cognitive and vascular problems, result from haploinsufficiency of NF1. In contrast, other symptoms are triggered by somatic NF1 mutation/loss of heterozygosity (LOH) resulting in biallelic NF1 inactivation. Further, transformation of plexiform neurofibromas (NFs) into malignant peripheral nerve sheath tumors (MPNSTs) involves additional genetic events. Abbreviations: juvenile myelomonocytic leukemias (JMML) and gastrointestinal stromal tumors (GIST). B. The major defining features of NF1 include: (i) Café-au-lait macules, (ii) cutaneous neurofibromas, (iii) axillary freckling, (iv) Lisch nodules, (v) plexiform neurofibromas, (vi) thinning of long bone cortex and (vii) optic pathway glioma. Adapted from [2].