Craniofacial anomalies in a murine model of heterozygous fibroblast growth factor 10 gene mutation.

OBJECTIVE: Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo-Auriculo-Dento-Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/- ) mutation at skeletal maturity. METHODS: Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/- mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro-computed tomography. Landmark-based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. RESULTS: The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/- mice (P < .05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P > .05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. CONCLUSION: The FGF10+/- mutation was associated with craniomaxillary skeletal hypoplasia that probably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, the skeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion.

Erosion-inhibiting potential of the stannous fluoride-enriched CPP-ACP complex in vitro.

Currently available anti-erosive agents only provide partial protection, emphasizing the need to enhance their performance. By characterizing erosive enamel wear at the nanoscale, the aim of this in vitro study was to assess the anti-erosive effects of SnF2 and CPP-ACP both individually and synergistically. Erosion depths were assessed longitudinally on 40 polished human enamel specimens after 1, 5, and 10 erosion cycles. Each cycle comprised one-min erosion in citric acid (pH 3.0) and one-min treatment in whole saliva (control group) or a slurry of one of the three anti-erosive pastes (10% CPP-ACP; 0.45% SnF2 (1100 ppm F); or SnF2/CPP-ACP (10% CPP-ACP + 0.45% SnF2)) (n = 10 per group). Scratch depths were assessed longitudinally in separate experiments using a similar protocol after 1, 5, and 10 cycles. Compared with the control groups, all slurries reduced erosion depths after 1 cycle (p ≤ 0.004) and scratch depths after 5 cycles (p ≤ 0.012). The order of anti-erosive potential was SnF2/CPP-ACP > SnF2 > CPP-ACP > control for erosion depth analysis, and SnF2/CPP-ACP > (SnF2 = CPP-ACP) > control for scratch depth analysis. These data provide 'proof of concept' evidence that SnF2/CPP-ACP has superior anti-erosive potential compared to SnF2 or CPP-ACP alone.

Prevalence and morphological features of molar-root incisor malformation in children attending a specialist paediatric dental unit.

BACKGROUND: Molar-root incisor malformation (MRIM) is a rare dental anomaly featuring constricted cervical margins and tapered, narrow root and pulp morphology, often associated with severe toothache and infection. AIM: The aim of this study was to determine the prevalence of MRIM in children seen in a specialist paediatric dental unit of a tertiary referral hospital and to describe the characteristics of affected individuals. DESIGN: This study was an audit of children attending from November 2020 to November 2021. Radiographs were used to identify individuals with MRIM, and clinical data were collated. In addition, histology and microcomputed tomography (microCT) imaging were performed on teeth extracted from an affected individual. RESULTS: The prevalence of MRIM was five cases of 1054 children examined (0.47% or 1:210). The permanent first molars were affected in all five children and the primary second molars in two children; all children had medical comorbidities and multiple exposures to general anesthesia before 4 years of age. In addition, histological and microCT analyses displayed numerous microchannels connecting the pulp chamber to the external surface of the tooth at the furcation. CONCLUSIONS: Molar-root incisor malformation is an uncommon dental anomaly affecting paediatric patients with multiple comorbidities and is characterized by porosities extending from the pulp chamber to the external tooth surface, predisposing the risk of bacterial ingress from the oral cavity into the pulp chamber. Early detection may prevent atypical odontogenic facial pain and infection.

Computed tomography assessment of hypodontia and crown size in hemifacial microsomia.

OBJECTIVE: Our aims were to assess the prevalence of hypodontia in unilateral hemifacial microsomia (HFM), and to compare tooth (crown) size between affected and unaffected sides. DESIGN: In a retrospective cross-sectional study of South Australians, computed tomography (CT) scans were used to assess hypodontia and crown size (mesiodistal length, buccolingual width and crown height). The inclusion criteria were the absence of other congenital anomalies and the availability of CT scans. The exclusion criteria were the lack of extraction history or reproducible landmarks for morphometric assessment. The final sample comprised 41 participants in both dentitions, including 32 children and 9 adults (median age 13.9 years, range 0.4 - 47.6 years; 19 males and 22 females). Hypodontia was assessed in all participants, and the permanent crown size in 30 (73.2%) participants. Linear mixed-effects models were performed to determine if crown size was significantly different between the two sides, controlling for sex, HFM severity, and tooth and jaw type. RESULTS: Hypodontia occurred in none of the participants in the primary dentition, but in 6/30 (20%) participants in the permanent dentition (3/30 each on the affected and unaffected sides). There was no significant difference in the mean crown dimensions between the two sides, but the crown size was larger in males (p < 0.05), except for mesiodistal length, and became progressively smaller with increased HFM severity (p < 0.05). CONCLUSIONS: Hypodontia spared the primary dentition but featured prominently in the permanent dentition. The permanent crown dimensions were unaltered between the two sides.

Effectiveness of photobiomodulation in reducing pain and producing dental analgesia: a systematic review.

PURPOSE: Photobiomodulation (PBM) is reported in many studies to produce dental analgesia without producing thermal damage to tissues. This systematic review aims to assess in vivo studies to support the statement that PBM can produce dental analgesia. METHOD: A systematic search strategy was constructed, and PubMed, Scopus, and Embase databases were searched. Subsequently, inclusion and exclusion criteria were applied, reference lists were scanned, and hand searched to identify other suitable studies. RESULTS: Five studies met the inclusion criteria. Meta-analysis was not undertaken due to the heterogenous nature of the studies and data. Positive analgesia outcome was obtained in four out of five studies, and one study with no significant results was criticized for poor reporting of laser parameters, small sample size (six). CONCLUSION: In general, all studies were criticized for poor discussion of all covariates that could have modified the results, consequently resulting in poor quality of evidence, moderate risk of bias, and poor internal validity, as well as external validity. The systematic review also discussed the potential implications of all variables to be considered for future trials, including pulsing mode, contact modes, and tooth characteristics.

Comparison of surface roughness of root cementum and orthodontically induced root resorption craters from high- and low-fluoridation areas: a 3D confocal microscopy study.

BACKGROUND: Fluoride has a major role in strengthening the structure of enamel against acids. Despite differences between caries and root resorption processes, both events inherently involve acidic dissolution of dental tissues. The aim of the present study was to investigate the effects of water fluoridation levels on the surface roughness of root cementum and resorption craters. The findings provided more insight into the influence of fluoride on the surfaces of intact cementum surface and resorption craters. METHODS: Twenty-eight orthodontic patients were recruited from two cities in Turkey, with high (≥ 2 ppm) and low (≤ 0.05 ppm) water fluoridation. These patients needed bilateral maxillary first premolar extraction as part of their orthodontic treatment and were allocated into two study groups (n = 14 in each group) based on water fluoridation exposure level: the high-fluoride group (HF) and low-fluoride group (LF). 150 g of buccal tipping forces was applied to all maxillary first premolar teeth for 12 weeks with a beta-titanium spring which was reactivated every 4 weeks. All maxillary premolars were removed at the end of the experiment for surface roughness assessment using three-dimensional confocal microscopy and the associated software. The buccal root surface and the largest buccal resorption crater were investigated. RESULTS: Resorption craters were significantly rougher in LF group compared to HF group (p = 0.002). Craters were rougher than the intact root surfaces (p = 0.000). Cervical and apical regions were significantly rougher than the middle region (p = 0.000 and p = 0.024, respectively). CONCLUSIONS: Higher water fluoridation level of ≥ 2 ppm resulted in significantly smoother root resorption craters than low water fluoridation level of ≤ 0.05 ppm when the teeth were subjected to 150 g of buccal tipping force. Fluoride seems to have a protective role at the interface of root resorption, and further mineral or histological studies may shed light on the exact protective process against root resorption.

Craniomaxillofacial morphology in a murine model of ephrinB1 conditional deletion in osteoprogenitor cells.

OBJECTIVE: EFNB1 mutation causes craniofrontonasal dysplasia (CFND), a congenital syndrome associated with craniomaxillofacial anomalies characterised by coronal craniosynostosis, orbital hypertelorism, and midface dysplasia. The aim of this murine study was to investigate the effect of the EfnB1 conditional gene deletion in osteoprogenitor cells on the craniomaxillofacial skeletal morphology. DESIGN: The skulls of male and female mice, in which EfnB1 was deleted by Cre (a site-specific DNA recombinase) under the control of the Osterix (Osx) promoter (EfnB1OB-/-), were compared to those without EfnB1 deletion (Osx:Cre control) at two ages (4 and 8 weeks; n = 6 per group). The three-dimensional micro-computed tomography reconstructions were prepared to calculate 17 linear measurements in the cranial vault (brain box), midface and mandible. Coronal and sagittal sutures from the 8-week-old mice were also subjected to histological examination. RESULTS: EfnB1OB-/- mice displayed significantly larger cranial height, larger interorbital and nasal widths, smaller maxillary width than controls by 8 weeks (p < 0.05), but mandibular size was not significantly different (p > 0.05). Binomial testing showed significantly smaller EfnB1OB-/- skulls at 4 weeks but larger at 8 weeks (p < 0.05). Histological examination revealed increased bony fusion and fibrous connective tissue deposition at the coronal suture of EfnB1OB-/- mice compared with controls. CONCLUSIONS: Craniofacial phenotype of the murine model of EfnB1 deletion in osteoprogenitor cells partially represents the human CFND phenotype, with implications for better understanding mechanisms involved in skeletal morphogenesis and malocclusion.

Craniofacial Phenomics: Three-Dimensional Assessment of the Size and Shape of Cranial and Dentofacial Structures.

Craniofacial phenomics has opened up numerous opportunities to correlate genetic and epigenetic factors to craniofacial phenotypes in order to improve our understanding of growth and development in health and disease. Three-dimensional (3D) imaging has played a key role in advancing craniofacial phenomics by facilitating highly sensitive and specific characterizations of craniofacial and dental morphology. Here we describe the use of micro-computed tomography (micro-CT) to image the murine craniofacial complex, followed by surface reconstruction for traditional morphometric analyses. We also describe the application of geometric morphometrics, based on Generalized Procrustes Analysis, for use in human premolars. These principles are interchangeable between various vertebrate species, and between various surface imaging techniques (including micro-CT and 3D surface scanners), offering a high level of versatility and precision for extensive phenotyping of the entire craniofacial complex.

Micro-CT-Based Bone Microarchitecture Analysis of the Murine Skull.

X-ray micro-computed tomography (micro-CT) imaging has important applications in microarchitecture analysis of cortical and trabecular bone structure. While standardized protocols exist for micro-CT-based microarchitecture assessment of long bones, specific protocols need to be developed for different types of skull bones taking into account differences in embryogenesis, organization, development, and growth compared to the rest of the body. This chapter describes the general principles of bone microarchitecture analysis of murine craniofacial skeleton to accommodate for morphological variations in different regions of interest.

Tooth wear development in the Australian Aboriginal dentition from Yuendumu: A longitudinal study.

The analysis of dental wear, at both the microscopic and macroscopic scale, is one of the most widely used tools in archeology and anthropology to reconstruct the diet and lifestyle of past human populations. Biomechanical studies have indicated that tooth wear helps to dissipate the mechanical load over the crown surface, thus reducing the risk of tooth fracture. To date, there are only a few studies that have examined functional tooth wear variation in modern humans. Here we propose to study masticatory efficiency through the use of the Occlusal Fingerprint Analysis method, a well-developed digital approach that allows the reconstruction of the occlusal dynamics occurring during mastication. The aim of this study is to provide the first longitudinal quantitative data of molar and premolar macrowear patterns within a functional context. We examined the mixed and permanent dentition of one Australian Aboriginal child (from ages 8 to 17) from Yuendumu, using high-resolution surface scans of dental casts including both upper and lower arches. Our results suggest that the occlusal macrowear patterns of this individual did not significantly change through time. Occlusal contact parameters such as functional area, inclination and direction remain relatively unaltered throughout childhood and adolescence, indicating little change in the masticatory function of this individual. The functional tooth wear pattern in this individual did not change longitudinally indicating the degree of masticatory efficiency has most probably remained unaltered.

A functional analysis of Carabelli trait in Australian aboriginal dentition.

OBJECTIVES: Carabelli is a nonmetric dental trait variably expressed as a small pit to a prominent cusp in the maxillary molars of modern humans. Investigations on the occurrence and expression rates of this trait have been conducted extensively, tracing its origin to genetic sources. However, there remains a lack of understanding about its potential role in chewing. In this study, we examine molar macrowear with the aim of reconstructing Carabelli trait occlusal dynamics occurring during chewing. METHODS: We have examined 96 deciduous and permanent maxillary molars of children and young adults from Yuendumu, an Australian Aboriginal population that was at an early stage of transition from a nomadic and hunter-gatherer way of life to a more settled existence. We apply a well-established method, called Occlusal Fingerprint Analysis, which is a digital approach for analyzing dental macrowear allowing the reconstruction of jaw movements required to produce wear pattern specific to each tooth. RESULTS: Carabelli trait slightly enlarges the surface functional area, especially in those molars where this feature is expressed in its cuspal form and it is closer to the occlusal plane. Moreover, the highly steep contact planes would also indicate that Carabelli wear areas contribute to increasing the shearing abilities of the occluded teeth, which are particularly important when processing fibrous and tough foods. CONCLUSIONS: The macrowear analysis suggests that Carabelli trait in the Aboriginal people from Yuendumu slightly enhanced occlusion and probably played some functional role during mastication. Future biomechanical and microwear analyses could provide additional information on the mechanical adaptation of Carabelli trait in modern human dentition.

Titania nanotube-based protein delivery system to inhibit cranial bone regeneration in Crouzon model of craniosynostosis.

BACKGROUND: Craniosynostosis is a developmental disorder characterized by the premature fusion of skull sutures, necessitating repetitive, high-risk neurosurgical interventions throughout infancy. This study used protein-releasing Titania nanotubular implant (TNT/Ti) loaded with glypican 3 (GPC3) in the cranial critical-sized defects (CSDs) in Crouzon murine model (Fgfr2c342y/+ knock-in mutation) to address a key challenge of delaying post-operative bone regeneration in craniosynostosis. MATERIALS AND METHODS: A 3 mm wide circular CSD was created in two murine models of Crouzon syndrome: (i) surgical control (CSDs without TNT/Ti or any protein, n=6) and (ii) experimental groups with TNT/Ti loaded with GPC3, further subdivided into the presence or absence of chitosan coating (on nanotubes) (n=12 in each group). The bone volume percentage in CSDs was assessed 90 days post-implantation using micro-computed tomography (micro-CT) and histological analysis. RESULTS: Nano-implants retrieved after 90 days post-operatively depicted well-adhered, hexagonally arranged, and densely packed nanotubes with average diameter of 120±10 nm. The nanotubular architecture was generally well-preserved. Compared with the control bone volume percentage data (without GPC3), GPC3-loaded TNT/Ti without chitosan coating displayed a significantly lower volume percent in cranial CSDs (P<0.001). Histological assessment showed relatively less bone regeneration (healing) in GPC3-loaded CSDs than control CSDs. CONCLUSION: The finding of inhibition of cranial bone regeneration by GPC3-loaded TNT/Ti in vivo is an important advance in the novel field of minimally-invasive craniosynostosis therapy and holds the prospect of altering the whole paradigm of treatment for affected children. Future animal studies on a larger sample are indicated to refine the dosage and duration of drug delivery across different ages and both sexes with the view to undertake human clinical trials.

Dentinal dysplasia type 1: A 3D micro-computed tomographic study of enamel, dentine and root canal morphology.

Dentine dysplasia type 1 is a rare and complex dental anomaly. Our aim was to conduct a morphometric assessment of a dentinal dysplasia type 1c (DD1c) caries-free mandibular second molar, extracted due to symptomatic apical periodontitis. Controls consisted of five intact mandibular second molars. Micro-computed tomography analysis showed that the DD1c volume % for enamel, dentine/cementum and pulp chamber fell in the 0.36th, 99.97th and 0.09th percentiles of the control teeth (P < 0.01). It also revealed an extremely complicated root canal system in the DD1c tooth with a varying degree of dentine mineralisation and aberrant dentine deposition in the pulp chamber. A crack extending from the external tooth surface to the pulp chamber was identified as a potential site for microbial invasion. Clinical implications include preventive measures and early intervention in reversible pulpitis. Conclusion: Micro-CT imaging can be useful in establishing post-extraction diagnosis of cracks and phenomic characterisation of tooth anomalies.

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.

Compensatory interactions between developing maxillary anterior teeth in a sample of twins.

OBJECTIVES: The objective of this study was to revisit the topic of compensatory interactions between maxillary anterior teeth during development advanced by Sofaer et al. (1971). We addressed the hypotheses listed by Sofaer and colleagues using data derived from our Australian twin sample to investigate whether final tooth size in permanent maxillary central incisors and canines showed evidence of developmental compensation for adjacent missing or microdont lateral incisors. Such compensation is one factor interacting in the complex system of dental development. MATERIALS AND METHODS: A 2D image analysis system was used to measure crown height from the labial view, labiopalatal crown width from the incisal view, and mesiodistal crown width from both the labial (MDl) and incisal (MDi) views of the permanent maxillary central incisors and canines on the dental study model of twins enrolled in a longitudinal study of dental development. RESULTS: Developmental variations of maxillary lateral incisors influence the morphogenesis of the adjacent teeth. For example, individuals with one missing lateral incisor and one lateral incisor of average dimensions, had significantly larger central incisors than the control group for the MDl and MDi dimensions (p < 0.05). Of the 7 monozygotic twin pairs, 6 were discordant in maxillary anterior hypodontia and microdontia, and 13 out of 14 dizygotic twin pairs were discordant. CONCLUSIONS: This study provides further evidence of developmental interactions in the maxillary anterior region, partially supporting Sofaer and colleagues' hypotheses. These interactions are part of a complex adaptive system involving genetic, epigenetic and environmental factors.

Technical note: The use of 3D printing in dental anthropology collections.

OBJECTIVES: Rapid prototyping (RP) technology is becoming more affordable, faster, and is now capable of building models with a high resolution and accuracy. Due to technological limitations, 3D printing in biological anthropology has been mostly limited to museum displays and forensic reconstructions. In this study, we compared the accuracy of different 3D printers to establish whether RP can be used effectively to reproduce anthropological dental collections, potentially replacing access to oftentimes fragile and irreplaceable original material. METHODS: We digitized specimens from the Yuendumu collection of Australian Aboriginal dental casts using a high-resolution white-light scanning system and reproduced them using four different 3D printing technologies: stereolithography (SLA); fused deposition modeling (FDM); binder-jetting; and material-jetting. We compared the deviations between the original 3D surface models with 3D print scans using color maps generated from a 3D metric deviation analysis. RESULTS: The 3D printed models reproduced both the detail and discrete morphology of the scanned dental casts. The results of the metric deviation analysis demonstrate that all 3D print models were accurate, with only a few small areas of high deviations. The material-jetting and SLA printers were found to perform better than the other two printing machines. CONCLUSIONS: The quality of current commercial 3D printers has reached a good level of accuracy and detail reproduction. However, the costs and printing times limit its application to produce large sample numbers for use in most anthropological studies. Nonetheless, RP offers a viable option to preserve numerically constraint fragile skeletal and dental material in paleoanthropological collections.

Three-dimensional (3D) geometric morphometric analysis of human premolars to assess sexual dimorphism and biological ancestry in Australian populations.

OBJECTIVES: This study aimed to investigate size and shape variation of human premolars between Indigenous Australians and Australians of European ancestry, and to assess whether sex and ancestry could be differentiated between these groups using 3D geometric morphometrics. MATERIALS AND METHODS: Seventy dental casts from each group, equally subdivided by sex, were scanned using a structured-light scanner. The 3D meshes of upper and lower premolars were processed using geometric morphometric methods. Seventy-two landmarks were recorded for upper premolars and 50 landmarks for lower premolars. For each tooth type, two-way ANOVA was used to assess group differences in centroid size. Shape variations were explored using principal component analysis and visualized using 3D morphing. Two-way Procrustes ANOVA was applied to test group differences for ancestry and sex, and a "leave-one-out" discriminant function was applied to assess group assignment. RESULTS: Centroid size and shape did not display significant difference between the sexes. Centroid size was larger in Indigenous Australians for upper premolars and lower second premolars compared to the Australians of European ancestry. Significant shape variation was noted between the two ancestral groups for upper premolars and the lower first premolar. Correct group assignment of individual teeth to their ancestral groups ranged between 80.0 and 92.8% for upper premolars and 60.0 and 75.7% for lower premolars. DISCUSSION: Our findings provide evidence of significant size and shape variation in human premolars between the two ancestral groups. High classification rates based on shape analysis of upper premolars highlight potential application of geometric morphometrics in anthropological, bioarcheological and forensic contexts.

Glypican-based drug releasing titania implants to regulate BMP2 bioactivity as a potential approach for craniosynostosis therapy.

Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies. This study presents the application of nanoengineered TNT/Ti implants loaded with recombinant glypicans for craniosynostosis therapy. By using Dual luciferase Reporter assay, we tested the biofunctionality of eluted glypicans from the TNT/Ti implants for BMP2 bioactivity regulation in C2C12 murine myoblast cell line. BMP2 activity was inhibited significantly for up to 15days by the glypicans released from polymer-coated TNT/Ti implants, indicating their potential application in adjunctive craniosynostosis treatment.

Extensive phenotyping of the orofacial and dental complex in Crouzon syndrome.

OBJECTIVES: Fibroblast growth factor receptor 2 (FGFR2) C342Y/+ mutation is a known cause of Crouzon syndrome that is characterised by craniosynostosis and midfacial hypoplasia. Our aim was to conduct extensive phenotyping of the maxillary, mandibular and dental morphology associated with this mutation. MATERIALS AND METHODS: Morphometric data were obtained from 40 mice, representing two genotypes (Crouzon and wild-type) and two sexes (males and females) (n=10 in each group). Dental analysis further categorised the first molars into the two jaws (maxillary and mandibular) (n=20 in each group). Maxillary, mandibular and dental morphology was compared by analysing 23 linear landmark-based dimensions in three-dimensional micro-computed tomography reconstructions. RESULTS: Compared with wild-type, Crouzon (FGFR2C342Y/+) maxillae were significantly shorter in maximum height, anterior and posterior lengths and middle width, but larger in posterior width (p<0.05 for height; p<0.001 for other comparisons). In the Crouzon mandible, the ascending and descending heights, effective and mandibular lengths, and intercoronoid and intercondylar widths were significantly shorter, whereas intergonial width was larger (p<0.01 for intercondylar width; p<0.001 for other comparisons). Crouzon teeth were significantly smaller mesiodistally, but larger in crown height (p<0.001 for each comparison). All Crouzon mice presented with bifid mandibular condyles and a quarter presented with expansive bone lesions in the mandibular incisor alveolus. CONCLUSIONS: Our findings of hypoplasia in all three planes in Crouzon maxillae and mandibles, together with the presence of bifid mandibular condyles and expansive bone lesions, may be relevant to maxillofacial surgery and orthodontics. Beyond skeletal effects, the FGFR2C342Y/+ mutation is now implicated in affecting tooth development. This study's skeletal phenomics data also provides baseline data against which the effect of various treatments can now be assessed.