The importance of PDE4D for human cognition is shown by ultra-rare, autosomal dominant mutations in PDE4D that cause acrodysostosis without hormone resistance (ACRDYS2), a neurodevelopmental syndrome causing short stature, brachydactyly (short fingers and toes), nasal hypoplasia and intellectual disability with speech and psychomotor retardation20,21. This evidence concerns the gene PDE4D and acrodysostosis 2 with or without hormone resistance.