No abstract

BackgroundThe purpose of this study was to elucidate the factors that cause facial asymmetry by comparing the characteristics of the mandibular morphology in patients with mandibular prognathism with or without facial asymmetry using three-dimensional computed tomography (3D-CT).MethodsWe studied 28 mandibular prognathism patients whose menton deviated by ≥ 4 mm from the midline (FA group, n = 14) and those with a < 4-mm deviation (NA group, n = 14). DICOM data from multislice CT images were reconstructed and analysed using 3D image analysing software. Mandibular structures were assessed via linear, angular, or volumetric measurements and analysed statistically.ResultsThe lengths of the ramal and body components and condylar volume in the FA group were significantly greater on the nondeviated side than those on the deviated side. The mandibular body length of the nondeviated side in the FA group was significantly longer than that of the NA group. Other components of the FA group did not significantly differ from those of the NA group.ConclusionsImbalances in the sizes of the ramal and body components as well as the increased body length of the nondeviated side in the FA group compared with that of the NA group may contribute to facial asymmetry in patients with mandibular prognathism.

The frontonasal mass gives rise to the facial midline and fuses with the maxillary prominence to form the upper lip. Here we focus on the regulation and function of TBX22, a repressor dynamically expressed in the frontonasal mass. Both FGF and Noggin (a BMP antagonist) strongly induce gTBX22, however, each has opposite effects on morphogenesis -Noggin inhibits whereas FGF stimulates growth. To determine whether TBX22 mediates these effects, we used retroviruses to locally increase expression levels. RCAS::hTBX22 decreased proliferation, reduced expression of MSX2 and DLX5 and caused cleft lip. Decreased levels of endogenous gTBX22 were also observed but were not the primary cause of the phenotype as determined in rescue experiments. Our data suggest that genetic or environmental insults such as those affecting the BMP pathway could lead to a gain-of-function of TBX22 and predispose an individual to cleft lip. Developmental Dynamics 239:458-473,

BackgroundThe purpose of this cross-sectional study was to investigate the effects of congenitally missing teeth on craniofacial morphology and to characterize the features of maxillofacial morphology of oligodontia patients associated with individual skeletal maturity by assessment with the cervical vertebrae maturation (CVM) method.MethodsA total of 106 non-syndromic Japanese patients with congenitally missing teeth (except for third molars) were selected and categorized into two groups according to the severity of congenitally missing teeth (hypodontia group, 1–5 missing teeth [n = 56]; oligodontia group, ≥ 6 missing teeth [n = 50]). A control group included orthodontic patients without either skeletal disharmony or congenitally missing teeth (n = 63). Subjects in oligodontia and control groups were further categorized into two subgroups on the basis of cervical stage (CS): stage I (CS2 or 3; n = 27 and n = 31, respectively) and stage II (CS4 or above; n = 23 and n = 32, respectively). Lateral cephalograms were analyzed by using eight angular and eight linear measurements. Z-scores were formulated on the basis of age and sex and were matched to the Japanese norm. Tukey tests and t tests were performed.ResultsCompared with the control group, the hypodontia group had significantly smaller U1 to FH plane angle and A-B plane angle; U1-L1 was significantly larger. The oligodontia group had significantly smaller ANS-Me, L1 to mandibular plane angle, and Ptm-A; U1-L1 was significantly larger. At stage I, the oligodontia group had significantly smaller ANS-Me, gonial angle, and ANS-U1. At stage II, the oligodontia group had significantly smaller U1 to FH plane angle, L1 to mandibular plane angle, Ptm-A, and Go-Pog; it also had significantly larger U1-L1.ConclusionsThe present study suggested that skeletal patterns differ along with the number of congenitally missing teeth and that, in oligodontia patients, skeletal patterns differ before and after growth peak. It is important to consider the skeletal characteristics of tooth agenesis patients when designing a treatment plan.

BackgroundTooth agenesis can involve one or more congenitally missing teeth (CMT) and is the most common congenital dental anomalies in humans. Tooth agenesis and reduction of mesiodistal tooth width are reportedly associated, suggesting that the pathogenesis of the two conditions is related. The current study analyzed the frequency of tooth agenesis and mesiodistal tooth width in cases of hypodontia (1–5 CMT) and oligodontia (≥ 6 CMT) in Japanese patients based on the hypothesis that reductions in mesiodistal tooth width are more frequently associated with oligodontia than hypodontia.MethodsJapanese patients with tooth agenesis were divided into hypodontia cases (60 female and 25 male, mean age 19.6 years, mean CMT number 1.31 ± 1.65) and oligodontia cases (26 female and 25 male, mean age 14.6 years, mean CMT number 8.07 ± 2.39). Controls included patients with a skeletal class I relationship and no CMT (female and 60 male, mean age 20.8 years). Dental casts and orthopantomograms were used to analyze the CMT frequency and mesiodistal tooth width for each group. The Kruskal-Wallis test, the Mann-Whitney U test, and Spearman’s rank correlation were used for statistical analysis.ResultsIn the hypodontia group, mandibular second premolars were the most frequently missing tooth type (25.9%), followed by mandibular and maxillary lateral incisors (19.4 and 17.1%, respectively). In the oligodontia group, mandibular second premolars were the most frequently missing tooth type (88.2%), followed by maxillary second premolars (87.3%) and first premolars (63.7%). In female subjects in the hypodontia group, only maxillary lateral incisors and mandibular first molars were significantly smaller than those of the female control subjects. In contrast, in the oligodontia group, more tooth types were significantly smaller than those of the control, for both sexes. Except for maxillary second premolars in female subjects, correlations were apparent for all tooth types in both sexes.ConclusionsCompared to hypodontia, more tooth types exhibited reduced mesiodistal tooth width in oligodontia. Correlations between CMT number and mesiodistal tooth width support the hypothesis that reduction of mesiodistal tooth width are more frequently observed in Japanese oligodontia patients than in Japanese hypodontia patients.

No abstract

The basic helix-loop-helix protein Twist, a transcriptional repressor, is essential for embryogenesis in both invertebrates and vertebrates. Haploinsufficiency of the human TWIST1 gene, which causes the craniosynostosis disorder Saethre-Chotzen syndrome (SCS), is related to failure to repress transcription of CDKN1A (which encodes p21/WAF1/CIP1), promoting osteoblast differentiation. We have examined the functional significance of natural TWIST1 variants present in craniosynostosis patients and in their healthy relatives. Both deletion and duplication variants of the glycine-rich tract Gly5AlaGly5 inhibited E2A (E12/E47)-dependent transcription of CDKN1A to a similar degree as wild-type protein, indicating that the length of this glycine tract is not critical for efficient transcriptional repression. We also evaluated a newly identified heterozygous TWIST1 variant (c.115C>G, encoding p.Arg39Gly), located within a putative nuclear localization signal (NLS), that was present in a child with mild SCS and her clinically unaffected father and grandmother. Unlike wild-type protein, this mutant required cotransfected E12 to localize to the nucleus, indicating that the NLS, including amino acid 39, is essential for nuclear localization; inhibition of E2A-dependent transcription of CDKN1A occurred normally. This analysis further dissects the structure-function relationships of TWIST and corroborates with phenotypic observations of disease expressivity.

Here, we examine the expression and regulation of the gene BAMBI, a kinase-deficient decoy receptor capable of interacting with type I bone morphogenetic protein (BMP) receptors in avian embryos. Initially, expression was limited to the endoderm during neurula and pharyngula stages. From embryonic day 3.5 (stage 20) and onward, BAMBI expression almost perfectly overlapped with known expression patterns for BMP4, particularly in the face and limbs. We performed bead implant experiments in the face to see which signals could be repressing or promoting expression of BAMBI. Our data point to retinoids and BMPs as being major positive regulators of BAMBI expression; however, fibroblast growth factor 2 acts to repress BAMBI. Furthermore, retinoic acid is likely to act directly on BAMBI as induction occurs in the presence of cycloheximide. The data suggested that BAMBI could be used to regulate Bmp signaling during tissue interactions that are an integral part of facial morphogenesis. Developmental Dynamics 237:1500 -1508, 2008.