Craniofacial abnormalities in a murine model of Saethre-Chotzen Syndrome

Background: Saethre-Chotzen Syndrome (SCS) is an autosomal dominant syndrome that occurs due to a mutation or deletion of the Twist1 gene at chromosome 7p21. Our aim was to conduct a morphometric analysis of the craniofacial features in the mouse associated with a Twist1^+/− mutation. Methods: Micro-computed imaging was conducted for the skulls of forty skeletally mature mice, equally distributed by sex (male and female) and two genotypes (Twist1^+/− or murine model of SCS; and Twist1^+/+ or wild-type). A morphometric analysis was carried out for eight parameters for the maxillary-zygomatico-temporal region, 10 parameters for the mandible and three parameters for teeth from three-dimensional reconstructions. Results: Compared with wild-type, the murine model of SCS showed these trends: (1) maxillary-zygomatico-temporal region, significantly shorter length and width posteriorly (p < 0.05), (2) mandible, significantly reduced height and width (p < 0.05), and (3) teeth, significantly shorter height, shorter mesio-distal width but longer bucco-lingual width (p < 0.05). In the murine model of SCS, the key morphological variations included incomplete ossification of the temporal bone and zygomatic arch, twisting and/or incomplete ossification of the palatal process of the maxilla, premaxilla and the ventral nasal concha, as well as bifid coronoid processes. Conclusions: The skeletal and dental alterations in the height, length and width provide a foundation for large-scale phenomics studies, which will improve existing knowledge of the Twist1 signalling cascade. This is relevant given the predicted shift towards minimally invasive molecular medical treatment for craniosynostosis.