The GoF MAX variants, the cause of polydactyly-macrocephaly syndrome, are present in the b-HLH-LZ domain, where the mutant MAX binds its target E-box sequence with a lower apparent affinity, leading to a more efficient heterodimerization with Myc and an increase in transcriptional activity of Myc (29). This evidence concerns the gene MYC and polydactyly-macrocephaly syndrome.