Patients with type-1 NF1 deletions often exhibit a severe clinical phenotype characterized by features that are not frequently seen in patients with intragenic pathogenic NF1 variants such as dysmorphic facial features, severe global developmental delay, cognitive disability, increased MPNST risk and a high number (as well as an accelerated growth rate) of neurofibromas (reviewed by Kehrer-Sawatzki et al. 2017, 2020; Ottenhoff et al. 2020; Büki et al. 2021; Pasmant et al. 2021; Pacot et al. 2021; Well et al. 2021). The gene discussed is NF1; the disease is malignant peripheral nerve sheath tumor.