SPRED1 and Legius syndrome: Heterozygous germline loss-of-function SPRED1 mutations have been described in patients affected by Legius Syndrome,5 which is a developmental disorder that shares the pigmentary phenotype of and some additional clinical features with Neurofibromatosis-1 (NF1).6 Both of these syndromes belong to the group of rasopathies or neuro-cardio-facial-cutaneous syndromes, which are caused by germline mutations that affect proteins involved in the Ras/MAPK pathway.3