NF1 and Leigh syndrome: Initially described as an NF1-like phenotype, LS is caused by mutations in SPRED1 (MIM 609291) [1], which encodes Spred1, a member of the Sprouty/Spred protein family [19] and, similarly to neurofibromin, a negative regulator of the Ras/MAPK signaling pathway [20,21].