IRF6 and van der Woude syndrome: Since then, a role for GRHL-signalling in craniofacial development has been shown in multiple vertebrate models, and loss-of-function mutations are implicated in human epithelial disease that affects the head region, such as age-related hearing loss [130], ectodermal dysplasia [126], and both syndromic [14] and non-syndromic [131,132] clefts of the secondary palate, where Grhl3 is thought to interact with the known causative gene in Van der Woude Syndrome, Interferon Regulatory Factor 6 (IRF6).