,44 Binding of PRRX1 to a specific sequence within the promoter of Msx2 was demonstrated in vitro,45 and in the mouse mandible, it has been shown that the requirement for a high level of BMP4 to induce expression of the homeobox gene Msx2 can be bypassed in a Prrx1−/−;Prrx2−/− genetic background, indicating that PRRX1 acts as a repressor in this context46; hence, if the same activity occurs in the cranial suture, the effect of a PRRX1 pathogenic variant would be to alleviate this repression, thus predisposing to craniosynostosis. Here, MSX2 is linked to craniosynostosis.