Currently, only six genes/loci [GLI1, GLI3, serine/threonine kinase like domain containing 1 (STKLD1), ZPA regulatory sequence (ZRS), pre-ZRS region, and a deletion of 240 kb from the sonic hedgehog signaling molecule (SHH) promoter] have been identified in isolated PPD cases and ZRS is, perhaps, the most special and well known (7–12). This evidence concerns the gene GLI3 and progressive pseudorheumatoid arthropathy of childhood.