In craniosynostosis distinctive craniofacial and oral growth patterns are to be expected. This study aims to determine maxillary anomalies in craniosynostosis patients with Muenke syndrome, Saethre-Chotzen syndrome or TCF12-related craniosynostosis, using a three-dimensional semi-automated setup measurement of digital dental casts. Symmetry analysis of the maxilla of craniosynostosis patients was performed with creation of a reference frame, a palatal mesh and a distance map. The outline of the palate was determined by landmarks with the use of a semi-automated technique and software algorithm and compared to healthy controls. All transverse dimensions were smaller in the craniosynostosis group compared to the. control group (p < 0.001; canine premolar right TCF12 p = 0.005). In Muenke syndrome, the palate was higher compared to the control group (left and right; p < 0.001). In Saethre-Chotzen syndrome, the palate was shallower (left p < 0.001; right p = 0.003) and the left palatal surface was smaller compared to the control group (p < 0.001). This retrospective case-control study indicates that Muenke syndrome, Saethre-Chotzen syndrome and TCF12-related craniosynostosis have distinctive maxillary characteristics compared to healthy controls. Muenke syndrome had a higher arched palate. and Saethre-Chotzen had a shallower palate compared to healthy controls. The intersurface distance (ISD) in both syndromes indicated a palatal anomaly.