The majority of acrodysostosis patients carry de novo mutations,11 although familial cases have been described.11,34,37 Neither the mutations in PDE4D or PRKAR1A are found at a specific locus within the genes, instead they are spread throughout the functional domains of the proteins, specifically the catalytic domain and UCR1 and UCR2 in PDE4D (Fig. 2) and the cAMP binding domains in PRKAR1A. Here, PRKAR1A is linked to acrodysostosis.