Given the spectrum of human midfacial anomalies associated with disrupted functions of TFAP2A (branchio-oculo-facial syndrome), TFAP2B (Char syndrome), and ALX1, ALX3 and ALX4 (frontonasal dysplasia), these findings link features of previously disparate disorders into a shared genetic hierarchy. This evidence concerns the gene ALX3 and Branchio-oculo-facial syndrome.