Journal of craniofacial genetics and developmental biology最新文献

While the dynamics of maxillo-mandibular allometry associated with treatment modalities available for the management of Class III malocclusions currently are under investigation, developmental aberration of the soft tissues in untreated Class III malocclusions requires specification. In this study, lateral cephalographs of 124 prepubertal European-American children (71 with untreated Class III malocclusion; 53 with Class I occlusion) were traced, and 12 soft-tissue landmarks digitized. Resultant geometries were scaled to an equivalent size and mean Class III and Class I configurations compared. Procrustes analysis established statistical difference (P < 0.001) between the mean configurations. Comparing the overall untreated Class III and Class I configurations, thin-plate spline (TPS) analysis indicated that both affine and non-affine transformations contribute towards the deformation (total spline) of the averaged Class III soft tissue configuration. For non-affine transformations, partial warp 8 had the highest magnitude, indicating large-scale deformations visualized as a combination of columellar retrusion and lower labial protrusion. In addition, partial warp 5 also had a high magnitude, demonstrating upper labial vertical compression with antero-inferior elongation of the lower labio-mental soft tissue complex. Thus, children with Class III malocclusions demonstrate antero-posterior and vertical deformations of the maxillary soft tissue complex in combination with antero-inferior mandibular soft tissue elongation. This pattern of deformations may represent gene-environment interactions, resulting in Class III malocclusions with characteristic phenotypes, that are amenable to orthodontic and dentofacial orthopedic manipulations.

Prenatal exposure to anticonvulsant medication has been shown to cause craniofacial dysmorphology, prenatal growth retardation, hypoplastic nails and phalanges, and visceral abnormalities. In this study we examined maxillary and mandibular stone dental casts (45) and panoramic radiographs (39) from 45 individuals with ages 4.5 to 22.0 years for changes in mesiodistal crown size of deciduous and permanent teeth, and the presence of dental anomalies. These individuals had been exposed prenatally to antiepileptic drugs (AEDs). Mesiodistal crown diameters were measured from the dental casts and converted into standard scores (Z), using published normative data from the University of Michigan Longitudinal Craniofacial Growth Series. A significant increase in mesiodistal crown dimensions of the posterior maxillary teeth was observed, specifically in primary molars and their permanent premolar successors, as well as permanent molars. Changes in tooth size were more common in females than in males. Dental maturity, assessed using the panoramic radiographs, was equal to chronologic age. An increased frequency of hypodontia was the only notable dental anomaly.

Craniosynostosis, the premature osseous obliteration of cranial vault sutures, can result from mutations in genes encoding components of growth factor signaling systems or the extracellular matrix (ECM). Little is known of the capacity of osteoprogenitor cells of the cranial sutures to divide or to synthesize ECM in situ. Osteoblasts derived from patients with prematurely fused sutures were reported to express alkaline phosphatase and osteocalcin at elevated levels, while proliferating at a rate comparable to control cells [DePollack et al., JBMR, 1996]; however, the suture osteoprogenitors, the population most likely to show proliferative abnormalities, were not present in the fused sutures used for this study. A model in which rat coronal sutures and associated bones develop normally in vitro, but in which sutures can be induced to fuse in the absence of dura mater, was used to examine cell proliferation and total protein synthesis in unfused sutures cultured in the presence of dura mater or in sutures induced to fuse in the absence of dura mater. Significantly increased cell proliferation was seen in suture cells prior to sutural obliteration, which returned to control levels as sutural fusion proceeded. Collagen synthesis in fusing sutures was elevated compared to non-fusing sutures and comparable to that seen in bone. Results indicated that in the absence of intercellular signals provided by the dura mater, suture cell proliferation increased initially, followed by increased synthesis of collagenous ECM within the suture and subsequent osseous obliteration of the suture. Thus factors originating in the dura mater affected suture cell proliferation and ECM production and were required for the maintenance of suture patency.

We report our preliminary observations in six fetal lambs that were surgically manipulated in utero to impede the blood flow of the carotid arteries and their branches, including the laryngeal artery, the anastomotic branch between the vertebral artery and the occipital artery, the auricularis and the transverse facial arteries. Between 115 and 117 days of gestation (term pregnancy 147 days), all ewes were placed under general anesthesia and mechanical ventilation. Their fetuses were exteriorized and catheters were placed in their femoral artery for blood gas sampling. A balloon occluder and a blood flow probe were placed on one internal carotid while the contralateral side was completely ligated. On the third day post surgery, the balloon occluder was inflated three times for 30 minutes each time at 30 minute intervals in the experimental fetuses. PO2, PCO2, pH, lactate and glucose were monitored during the study. At 7 days post occlusion, all animals were sacrificed and tissues were collected. Craniofacial anomalies were obvious in three animals similar to those seen in hemifacial microsomia, Goldenhar syndrome and Pierre-Robin sequence. All three control animals had normal craniofacial structures. This preliminary data suggests that late gestation vascular disruptions may lead to significant craniofacial anomalies, as seen in our animal model.

An earlier puzzling observation [Shields and Mann, J Craiofac Genet Dev Biol, 16:126-136, 1996] that the prevalence of a polymorphic male predominate, major salivary gland-associated, static lesion of the mandible increased exponentially from the Arctic to the Tropics was explained by both positive and negative selection (balancing) on major salivary gland endocrine and exocrine factors. Additional prevalence rates presented here identified three high prevalence high-Temperate zone cultures that were unusually exposed to alimentary parasites. A correlation between macroparasite exposure and the mandibular lesion helped refine the potential selective forces that fashioned major salivary gland size variation. The data suggests that positive selection occurred for androgen-induced enlargement of the suite of major salivary glands and consequently increased quantities of factors. Increased quantities of salivary gland biologically active factors enhance innate protection against infestation of macroparasites per se, especially gut parasites. The data further suggests that negative selection against enlarged salivary glands occurred as protection against electrolyte imbalances in electrolyte stressed environments and in females.

Ovariectomy (OVX) and orchiectomy (ORX) are well known to increase bone turnover; however, the influences on condylar remodeling are not fully understood. The purpose of this study was to examine histological changes of the mandibular condyles in OVX and ORX mice in comparison to the femora. Eighty 8-week-old mice were used in this study. In each of the experimental and control groups, five mice were sacrificed 2, 4, 8, and 12 weeks after surgery for OVX and ORX. Histological changes of the mandibular condyle were studied in comparison to the femur, which is liable to undergo the influences of OVX and ORX. The number of TRAP-positive cells and the thickness of articular cartilage layer were also quantified. TRAP-positive cells in the condylar head of OVX and ORX mice exhibited the most prominent increase 4 weeks after the surgery and approached the control levels at the later experimental stages. Trabecular bone volume in the condyle of the OVX and ORX mice also decreased, although the rate was less than in the femora. It is shown that influences of OVX on the remodeling of femora appear earlier than those of ORX, whereas OVX and ORX affect the remodeling of condyle during the same growth period. It is also demonstrated that the influences of OVX and ORX are less in the condyle than in the femora. These findings emphasize that the influences of OVX and ORX on bone remodeling are varied by sexual difference and the type of bones.

Normal facial growth and development was analyzed through indirect anthropometry in a mixed longitudinal and cross-sectional investigation; 2,023 examinations were performed on 1,156 healthy Caucasian children and adolescents between 6 and 17 years of age and on 191 young adults. Three-dimensional coordinates of 22 facial landmarks were collected with the Three-Dimensional Facial Morphometry method by automated infrared photogrammetry. Selected three-dimensional parameters (linear distances, angles, and a ratio), describing facial height, width, depth, and convexity on the horizontal plane, were calculated and averaged for age and sex. Within each age group, most linear distances were significantly larger in males than in females, with some exceptions in the 11 to 12 age group, where female growth velocity showed a spurt. In females of the 14 to 15 age group the face had almost completed growth; in males of the same age group, a large increase was still to occur to attain adult values. The sexual dimorphism of the parameters calculated did not appear in the different parts of the face to the same extent: a large part of male facial preponderance occurred in the lower third of face. From 6 years of age to adulthood, the soft-tissues in the facial lower third increased by about 23% (males) and 17% (females), in the middle third by about 18% (males) and 13% (females), and in the upper third by about 16% (males) and 9% (females). The male vs. female comparisons within each age group suggested a sexual dimorphism in the timing of soft-tissue facial growth, but an overall similar attainment of different adult dimensions.

An histological and histochemical study analyzing cell density and distribution of extracellular matrix (ECM) components in two stages of developing secondary palate and in two strains of mice with different H-2 backgrounds was undertaken to investigate differences between a strain that is susceptible to glucocorticoid-induced cleft palate (A/Sn) and one that is resistant (C57/BL). In addition, the influence of dexamethasone treatment on ECM components was evaluated. A/Sn strain had significantly higher mesenchymal cell density compared to C57/BL at 13 days of gestation when the palatine processes are in vertical position. This difference in cell density was not significant at 14 days when palatal processes have been elevated. Dexamethasone did not alter cell density in both strains. A computer-assisted method utilizing image registration was used to compare the distribution of ECM components as judged by the stain intensity. Hyaluronate and collagen were higher in mesenchymal tissue of the palatine processes at 13 days of gestation in the C57/BL than in the A/ Sn strain. No differences in either hyaluronate or collagen were found in either strain and 14 days of development and dexamethasone treatment decreased these compounds in both strains. No differences were observed in laminin and type IV collagen of the basal lamina between strains in any of the stages studied. The results suggest that hyaluronic acid and collagen may be involved in different susceptibility to cortisone-induced cleft palate in the mouse.

The goal of this study is to characterize the differences between normal cranial morphology and that of patients diagnosed with isolated sagittal synostosis, using three-dimensional (3D) landmark coordinate data collected from computed tomography (CT) scans. This retrospective study uses pre-operative CT images of a sample of children diagnosed with isolated sagittal synostosis (N = 23) and of dry skulls of unaffected children (N = 10). In order to be included in the study, patients had to have a confirmed diagnosis of sagittal synostosis and a pre-operative CT scan of acceptable quality available in digital format. Separation of normal and synostosed individuals on the basis of craniofacial morphology was achieved by applying a principal coordinates analysis to a dissimilarity matrix calculated from the landmark coordinate data. Direct comparison of age-graded samples of normal and synostosed individuals using Euclidean Distance Matrix Analysis enabled localization of the morphological differences between samples. This method was also used to characterize growth patterns of the two samples using cross-sectional data. The parietal bosses were found to be the features that were most influential in separating sagittal synostosis patients from their age-matched normal counterparts. A cross-sectional analysis of growth showed that the specifics of the growth differences between normal and sagittal synostosis individuals changed with the age interval considered. We present direct evidence that the parietal bosses are critical in the differentiation of normal and sagittal synostosis morphology, and indirect evidence of the possible role of the parietal tubers in the etiology of sagittal synostosis.