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.

The Influence of Chorion Type on Health Measures at Birth and Dental Development in Australian and Dutch Twins: A Comparative Study.

Chorion type may significantly influence the prenatal environment of twins. This study explored the associations between chorion type and gestational age, birth weight, birth length, and the timing of emergence of the first primary tooth in two populations of twins, Australian and Dutch. Additionally, we investigated the relationship between chorion type and birth weight discordance (BWD) in order to determine whether a significant relationship existed between discordance in birth weight and discordance in the timing of emergence of the first primary tooth. The two study samples consisted of 409 Australian twin pairs and 301 Dutch twin pairs, all of European ancestry. Data were collected through a combination of questionnaires and recording charts administered to the parents and through linkage with biological databases. In the Australian sample, monozygotic monochorionic (MZMC) twins experienced the shortest mean gestation time (35 weeks), the lowest mean birth length (46 cm) and the lowest mean birth weight (2.3 kg) compared with other twin groups. For the same variables in the Dutch sample, these trends with MZMC twinning were not observed. Chorion type did not significantly affect the mean timing of emergence of the first primary tooth in either sample. Monochorionicity was found to be significantly associated with BWD in both samples, but there was a significant association between BWD in MZMC twin pairs and timing of emergence of the first primary tooth only in the Australian sample. Results from this study support previous findings that the timing of emergence of the first primary tooth is influenced strongly by genetic factors and is well protected from environmental disturbances.

Infraocclusion: Dental development and associated dental variations in singletons and twins.

OBJECTIVE: The aim of this study was to investigate the prevalence of selected dental variations in association with infraocclusion, as well as determining the effects of infraocclusion on dental development and tooth size, in singletons and twins. DESIGN: Two samples were analysed. The first sample comprised 1454 panoramic radiographs of singleton boys and girls aged 8-11 years. The second sample comprised dental models of 202 pairs of monozygotic and dizygotic twins aged 8-11 years. Adobe Photoshop CS5 was used to construct reference lines and measure the extent of infraocclusion (in mm) of primary molars on the panoramic radiographs and on 2D images obtained from the dental models. The panoramic radiographs were examined for the presence of selected dental variations and to assess dental development following the Demirjian and Willems systems. The twins' dental models were measured to assess mesiodistal crown widths. RESULTS: In the singleton sample there was a significant association of canines in an altered position during eruption and the lateral incisor complex (agenesis and/or small tooth size) with infraocclusion (P<0.001), but there was no significant association between infraocclusion and agenesis of premolars. Dental age assessment revealed that dental development was delayed in individuals with infraocclusion compared to controls. The primary mandibular canines were significantly smaller in size in the infraoccluded group (P<0.05). CONCLUSION: The presence of other dental variations in association with infraocclusion, as well as delayed dental development and reduced tooth size, suggests the presence of a pleiotropic effect. The underlying aetiological factors may be genetic and/or epigenetic.

Prevalence and patterning of maxillary premolar accessory ridges (MxPARs) in several human populations.

We present new data on the prevalence and patterning of the maxillary premolar accessory ridge (MxPAR), a common but understudied morphological dental trait that is expressed as a linear elevation extending from the buccal cusp ridge to the medial sulcus of maxillary premolar teeth. A total of 579 sets of dental casts, representing six ethnic groups, were scored using the five-grade system proposed by Burnett et al. (2010). The frequency and distribution of the MxPAR were determined by tooth type, sex, side, locus and ethnicity, and the applicability of the scoring system was assessed. The MxPAR was found in approximately two-thirds of premolar teeth, more often on second than first premolars, and more often on the distal aspect of the occlusal surface than the mesial. There was some evidence that more pronounced forms of the feature occurred more often in males than females, and that there may be some directionality in its expression between sides. Variation was also noted in the frequency of occurrence and degree of expression of the MxPAR between ethnic groups. Intra- and inter-observer concordance rates for scoring the MxPAR were low, confirming that it was difficult to score the trait identically on two different occasions. Our findings have clarified the distribution of the MxPAR within the dentition and between ethnic groups, and highlighted the need for researchers to carry out thorough replicability studies and to decide on an appropriate breakpoint for determining presence or absence of this feature before embarking on genetic studies or bio-distance analyses.

Genetic, epigenetic, and environmental influences on dentofacial structures and oral health: ongoing studies of Australian twins and their families.

The Craniofacial Biology Research Group in the School of Dentistry at The University of Adelaide is entering an exciting new phase of its studies of dental development and oral health in twins and their families. Studies of the teeth and faces of Australian twins have been continuing for nearly 30 years, with three major cohorts of twins recruited over that time, and currently we are working with twins aged 2 years old to adults. Cross-sectional data and records relating to teeth and faces of twins are available for around 300 pairs of teenage twins, as well as longitudinal data for 300 pairs of twins examined at three different stages of development, once with primary teeth, once at the mixed dentition stage, and then again when the permanent teeth had emerged. The third cohort of twins comprises over 600 pairs of twins recruited at around birth, together with other family members. The emphasis in this third group of twins has been to record the timing of emergence of the primary teeth and also to sample saliva and dental plaque to establish the timing of colonization of decay-forming bacteria in the mouth. Analyses have confirmed that genetic factors strongly influence variation in timing of primary tooth emergence. The research team is now beginning to carry out clinical examinations of the twins to see whether those who become colonized earlier with decay-forming bacteria develop dental decay at an earlier age. By making comparisons within and between monozygotic (MZ) and dizygotic (DZ) twin pairs and applying modern molecular approaches, we are now teasing out how genetic, epigenetic, and environmental factors interact to influence dental development and also oral health.

Anatomical relationships within the human pterygomandibular space: Relevance to local anesthesia.

A thorough understanding of the anatomy of the pterygomandibular space is fundamental to the successful administration of inferior alveolar nerve (IAN) blocks, which are frequently used in dentistry for mandibular anesthesia. However, the nature and extent of anatomical variations and relationships within this space are not well documented, and descriptions vary within the literature. This study analyzed the anatomical patterns and relationships of structures in the pterygomandibular space of 56 human cadaver hemi-heads, with both left and right sides from 10 individuals being available, and described the range of variability. In most cases, the IAN was anterior to the inferior alveolar vasculature with the inferior alveolar vein(s) being closest to the bone. On average, there were two veins per specimen. The position of the inferior alveolar neurovascular bundle expressed as the ratio of its distance from the anterior border of the ramus to the total anteroposterior length of the ramus was 0.60 (standard deviation [SD] = 0.07). The distance of anterior and medial displacement of the lingual nerve to the IAN was 7.3 mm (SD = 2.4 mm) and 3.9 mm (SD = 1.6 mm), respectively. The direct distance between the IAN and lingual nerve was 8.5 mm (SD = 2.4 mm). The sphenomandibular ligament always appeared dense and fibrous, medial to the neurovascular bundle. This anatomical study highlights the extent of variations in the positioning of anatomical structures directly relevant to IAN blocks, and reassesses the rationale for the direct approach, which is currently taught and practiced throughout many countries.

A three-dimensional computed tomography analysis of craniofacial asymmetry in malaysian infants with cleft lip and palate.

BACKGROUND: The application of three-dimensional computed tomography (3D CT) to analyse craniofacial morphology in individuals with cleft lip and palate (CLP) enables detailed assessments to be made of asymmetry in the region of the cleft and in regions distant from the cleft. The aim of this study was to compare craniofacial morphology in a sample of Malaysian infants with unoperated CLP with a control sample of unaffected Malaysian infants. METHODS: The study sample comprised 29 individuals: 10 with unilateral CLP (UCLP), 5 with bilateral CLP (BCLP), 7 with cleft lip and primary palate (CLPP), and 7 with isolated cleft palate (ICP). The control sample consisted of 12 non-cleft (NC) infants. All subjects were between 0.4 and 12.2 months of age. Nine mid-facial and 4 nasal bone landmarks were located on 3D CT scans and compared to a midline reference plane, which was created using the landmarks basion, sella, and nasion. Unpaired t tests and F tests were used to compare means and variances between sample groups, whereas paired t tests were used for comparisons within the UCLP and NC groups. RESULTS: Differences in variances of some mid-facial breadths and nasal bone dimensions were found in both male and female cleft groups when compared to the NC sample. In the UCLP group, some nasal bone and facial breadth dimensions were larger than in the NC sample and the nasal bone tended to deviate to the contralateral side of the cleft. CONCLUSION: CLP affects the size and orientation of the nasal bones and is associated with an altered morphology of some facial bones at positions distant from the region of the cleft.