Identification of a Novel Vomer Phenotype in the Fgfr2c C342Y/+ Mouse Model of Crouzon Syndrome

Crouzon syndrome has been linked with several FGFR2 mutations, including the Cys342Tyr mutation. The Fgfr2c C342Y/+ mouse model displays many of the phenotypic traits associated with Crouzon syndrome, including premature coronal suture fusion, a dome shaped neurocranium, and midfacial retrusion. This study was designed to perform a systematic evaluation of the morphological variation of the vomer in 3D micro‐computed tomography (3DμCT) scans of Fgfr2c C342Y/+ mice and their unaffected littermates. Vomer morphology was evaluated in mice at three ages: E17.5, P0, and P2. First, 3D reconstructions and slice images of 3DμCT scans were evaluated for evidence of bridging or fusion between the presphenoid bone and either the left or right vomer alae (N=81 Fgfr2c C342Y/+ mice, 92 unaffected littermates). None of the unaffected mice at any age exhibited any bridging or fusion between the vomer alae and presphenoid bone, while affected mice were increasingly likely to show bridging or fusion as age progressed. At P2, 60% of affected mice exhibited at least unilateral bridging between one of the vomer ala and the presphenoid. Second, geometric morphometric analysis was conducted on a set of 6 3D landmarks describing vomer shape, including landmarks on the vomer body and tips of the left and right alae (N=45 Fgfr2c C342Y/+ mice, 55 unaffected littermates). Mann‐Whitney U testing revealed that at each of the three ages tested, the anteroposterior lengths of the vomer bodies and vomer alae were significantly longer ( p < 0.05) and the mediolateral distance between the tips of the vomer alae was also significantly increased ( p < 0.001) in Fgfr2c C342Y/+ mice as compared to their unaffected littermates. The vomer is an element of the dermatocranium that interfaces with elements of the cranial base and the facial skeleton, which are components of the endocranium. This novel phenotype provides insight into the morphogenesis of the complex craniofacial traits typically associated with Crouzon syndrome and suggests the importance of evolutionary considerations in the interpretation of dysmorphogenesis associated with this FGFR2 mutation. Support or Funding Information This research was supported in part by NIDCR/NIH R01DE018500 R01DE022988 NICHD/NIH P01HD078233 and NSF BCS 1731909. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .