Comparison of Mandibular Volume and Linear Measurements in Patients with Mandibular Asymmetry.

In patients with mandibular asymmetry, the volume of the mandible divided by the mandibular median plane is significantly larger on the non-deviated (N-Dev) side than on the deviated (Dev) side. However, it has been reported that there is no significant difference between the volumes of the N-Dev and Dev sides when the mandibular ramus and body are divided. The purpose of this study was to investigate which region is responsible for the volume difference between the N-Dev and Dev sides. Cone Beam Computed Tomography (CBCT) images of patients with mandibular asymmetry were analyzed by measuring the volume, and linear analysis of the mandibular body, ramus, and condyle on the N-Dev and Dev side was performed. In this study, CBCT images of 37 patients (8 Japanese, 16 Korean, and 13 Egyptian) aged ≥ 18 years with mandibular asymmetry (men: 20, women: 17) were used to evaluate mandibular asymmetry. In patients with mandibular asymmetry, the N-Dev side showed significantly larger values than the Dev side for both volume and linear condyle, ramus, and mandibular body measurements. These results do not differ according to sex or ethnicity. Therefore, it is suggested that the N-Dev side of mandibular asymmetry is large without any regional specificity in pathophysiology.

Methods in Genetic Analysis for Evaluation Mandibular Shape and Size Variations in Human Mandible.

ABSTRACT: The human mandible has been investigated from both clinical and evolutionary perspectives. Recent advances in genome science have identified the genetic regulation of human mandibular shape and size. Identification of genes that regulate mandibular shape and size would not only enhance our understanding of the mechanisms of mandibular growth and development but also help define a strategy to prevent mandibular dysplasia. This review provides a comprehensive summary of why and how the mandible was evaluated in the human mandible genome study. The variation in human mandibular shape and size has been progressively clarified, not only by focusing on the mandible alone but also by using extremely diverse approaches. The methods of data acquisition for evaluating human mandibular shape and size variation are well established. Furthermore, this review explains how to proceed with future research.

Three-dimensional evaluation of mandibular volume in patients with cleft lip and palate during the deciduous dentition period.

OBJECTIVES: To examine the relationship between mandibular volume and craniofacial morphology in patients with cleft lip and palate using cone beam computed tomography (CBCT) and to compare these findings with control (noncleft) patients undergoing CBCT for other purposes during the deciduous dentition period. MATERIALS AND METHODS: Eighty-four patients were categorized into the unilateral cleft lip and alveolus (UCLA) group (n = 25; mean age, 4.60 ± 0.40 years), unilateral cleft lip and palate (UCLP) group (n = 23; mean age, 4.52 ± 0.39 years), bilateral cleft lip and palate (BCLP) group (n = 22; mean age, 4.54 ± 0.37 years), and control group without cleft (n = 14; mean age, 5.19 ± 0.52 years). Mandibular volume and craniofacial cephalometric measurements were obtained using CBCT. All measurements were assessed by analysis of covariance (ANCOVA) using Bonferroni post hoc pairwise comparison tests. RESULTS: ANCOVA revealed no statistically significant differences in mandibular volume among the groups. SNA° and ANB° were significantly larger in the UCLA and BCLP groups than in the control group. SN-MP° was smallest in the UCLA group. Co-A in the UCLP group was shorter than in the UCLA and BCLP groups. Go-Gn was shortest in the UCLP and BCLP groups compared with the control group. CONCLUSIONS: Three-dimensional evaluation of craniofacial morphology using CBCT can provide valuable information on malocclusion and other dentoskeletal problems among patients with CLP.

Three-dimensional assessment of the pharyngeal airway in Japanese preschoolers with orofacial clefts.

OBJECTIVES/HYPOTHESIS: Individuals with orofacial clefts often experience respiratory problems because of nasopharyngeal abnormalities. Pharyngeal airway morphology is thought to differ among the various cleft types. We measured three-dimensional (3D) airway volume using cone-beam computed tomography (CBCT) analysis to evaluate and compare pharyngeal airways in Japanese preschoolers with and without orofacial clefts. STUDY DESIGN: Retrospective case-control study. METHODS: We enrolled 83 subjects (37 boys, 46 girls; mean age = 4.66 ± 0.56 years) with nonsyndromic orofacial clefts and 16 noncleft healthy subjects (seven boys, nine girls; mean age = 5.30 ± 0.52 years) as controls. The subjects were divided into five groups. Four groups were based on the cleft type: isolated cleft palate, unilateral cleft lip and alveolus), unilateral cleft lip and palate, and bilateral cleft lip and palate. The fifth group included the noncleft controls. All subjects were examined with CBCT, and the 3D airway volume was measured. We analyzed group differences statistically using analysis of covariance with the Bonferroni post hoc pairwise comparison tests for the corrected means. RESULTS: Compared with the noncleft group, each cleft group exhibited significantly decreased total and nasal airway volumes and increased superior and inferior pharyngeal airway volumes. The differences were all statistically significant. CONCLUSIONS: Our findings suggest that anatomical differences exist in pharyngeal airway volumes among various cleft groups and in those without a cleft. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:533-540, 2020.

Comparison of condylar size among different anteroposterior and vertical skeletal patterns using cone-beam computed tomography.

OBJECTIVES: To compare condylar size among different anteroposterior and vertical skeletal patterns using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The study included 166 subjects (61 men, mean age: 27.2 ± 7.6 years; 105 women, mean age: 27.4 ± 9.2 years). The anteroposterior skeletal patterns of the subjects were classified into Classes I (-1° ≤ A point-nasion-B point angle [ANB] < 4°), II (ANB ≥ 4°), and III (ANB < -1°). The vertical skeletal patterns were classified into hypodivergent (mandibular plane [MP] ≤ 23°), normodivergent (23° < MP < 30°), and hyperdivergent (MP ≥ 30°) groups. The condylar length, height, and width were examined using CBCT images. Analysis of covariance was used to compare three condylar size measurements among the three anteroposterior groups and the three vertical groups using sex as a covariate. Both left and right sides were examined. Nine groups were further divided according to the anteroposterior and vertical groups, and two-way analysis of covariance (ANCOVA) was applied to estimate the composite effect of skeletal patterns in both directions. RESULTS: Sex as a covariate showed statistical significance in most examinations. The condylar height on both sides had statistically different anteroposterior skeletal patterns ( P < .001). The condylar width on both sides also had statistically different vertical skeletal patterns ( P < .001). After adjusting for sex, the condylar height and width on both sides increased from Class II, Class I, and Class III. The condylar width on both sides increased from the hypodivergent group, the normodivergent group, and the hyperdivergent group. No composite effect of skeletal patterns in both directions was observed. CONCLUSIONS: Condylar height and width considerably differed among subjects with different anteroposterior or vertical skeletal patterns. The anteroposterior or vertical skeletal patterns independently affected the condylar size.

Orthognathic surgery induces genomewide changes longitudinally in DNA methylation in saliva.

OBJECTIVE: Orthognathic surgery dramatically changes morphology of the maxillofacial deformity and improves the malocclusion morphologically and functionally. We investigated the influence of orthognathic surgery on genomewide DNA methylation in saliva. METHODS: Saliva was obtained from nine patients undergoing orthognathic surgery and two healthy reference individuals before and 3 months after orthognathic surgery. Genomewide DNA methylation profiling of saliva (341,482 CpG dinucleotides) was conducted using Infinium HumanMethylation450 BeadChips. RESULTS: Comparison between pre- and postsurgery saliva samples revealed significant changes in DNA methylation patterns at 2,381 CpG sites (p < 0.01) with suggestive significance. The differentially methylated probe sets were significantly associated with the cancer pathway (p = 2.8 × 10-7 ; a false discovery rate q-value = 3.7 × 10-4 ) and PI3K-Akt signalling pathway (p = 2.4 × 10-5 ; a false discovery rate q-value = 3.1 × 10-2 ). CONCLUSION: Pathway enrichment analysis of genes with suggestive significance demonstrated that altered DNA methylation in saliva of patients undergoing orthognathic surgery, possibly as a response to surgical stress or bone injury. Further studies with a large sample size and long-term observation are needed to validate the phenomena identified in this study.

Association between the FGFR1 rs13317 single nucleotide polymorphism and orbitale-nasion depth based on cephalometric images.

The fibroblast growth factor receptor 1 (FGFR1) gene plays an important role in craniofacial morphogenesis. In our previous study, an association between FGFR1 single nucleotide polymorphisms (SNPs) and craniofacial morphology was demonstrated in Japanese and Korean subjects. The present study aimed to evaluate the relationship between a common FGFR1 SNP (rs13317) with craniofacial morphology, increasing the number of measurements and examining Egyptian subjects (n = 191) in addition to the Japanese (n = 211) and Korean (n = 226) subjects. Genotyping for rs13317 was performed using the TaqMan assay, and its associations with 81 craniofacial measurements derived from lateral and posteroanterior cephalograms were analyzed by multiple regression analysis controlling sex and facial size. The results from each of the populations were then statistically combined. In the Egyptian subjects, rs13317 was significantly associated with the nasion-orbitale depth (P = 0.00040), and a suggestive association was also observed in the Japanese (P = 0.037) and Korean subjects (P = 0.045). The combined analysis revealed that only the nasion-orbitale depth showed a significant association (P = 0.000062) and that several measurements showed a suggestive association. Our results strongly indicate that rs13317 is associated with a smaller depth between the nasion and orbitale, representing a relative protrusion of the cheekbones and retrusion of the nasal root. A similar characteristic is also observed in individuals with Pfeiffer syndrome, which is caused by a dysfunctional FGFR1 mutation.

Growth hormone receptor gene is related to root length and tooth length in human teeth.

OBJECTIVES: To examine the relationship between tooth length and growth hormone receptor (GHR) gene variants in a healthy Japanese population. MATERIALS AND METHODS: The subjects consisted of 193 Japanese adults (69 men, 124 women), aged 13 to 56 years. Genomic DNA was extracted from saliva and genotyped GHR rs6184 and rs6180 variants using the Taqman genotyping. Computed tomography (CT) images were acquired using a dental cone-beam CT scanner and reconstructed using open-source OsiriX medical image processing software. The maxillary (upper; U) and mandibular (lower, L) central incisors (1), lateral incisors (2), canines (3), first premolars (4), second premolars (5), first molars (6), and second premolars (7) were evaluated. Teeth were assessed for crown height (CH), root length (RL), overall tooth length (C+R), and crown to root ratio (C/R). The relationships between GHR variants and CH, RL, C+R, and C/R were statistically examined. RESULTS: The GHR variant rs6184 was associated with the root lengths and tooth length for the upper and lower lateral incisors and upper canines (U2 RL; U3 RL, C+R; L2 RL [ P < .05]). CONCLUSIONS: The results indicate that the GHR rs6184 variant is associated with tooth length and ratio dimensions in a Japanese cohort. Further studies utilizing a larger sample size are needed to confirm this finding.

Relationship between tooth length and three-dimensional mandibular morphology.

OBJECTIVES: To clarify the relationship between tooth length and three-dimensional mandibular morphology in a healthy Japanese population. MATERIALS AND METHODS: This study included 181 Japanese adults: 66 men and 115 women. Cone-beam computed tomography (CBCT) images were acquired with a dentofacial cone-beam x-ray CT scanner. Tooth length was measured with open-source OsiriX medical image processing software. Crown height and root length were measured in the maxillary and mandibular central incisors, lateral incisors, canines, first premolars, second premolars, first molars, and second molars. Based on these measurements, principal component (PC) analysis was performed. The following measurements were used to assess three-dimensional mandibular morphology: CD-GO, GO-GN, RCD-LCD, RGO-LGO, RCP-LCP, and the gonial angle. Stepwise multiple regression analysis was performed to examine the associations between three-dimensional mandibular morphology and the patterns of crown and root lengths using the mandibular measurements as explanatory variables and each PC as the dependent variable. RESULTS: CD-GO was positively associated with PC1, which represented overall tooth length. RGO-LGO was positively associated with PC2, whereas GO-GN, RCP-LCP, and gonial angle were negatively associated with PC2, which was the axis denoting relatively longer root (+) vs higher crown (-). Being female was associated with PC3, which was the axis denoting relatively longer posterior tooth (+) vs anterior tooth (-). CONCLUSIONS: The present clinical study effectively used CBCT images and PC analysis to reveal significant correlations between tooth length and mandibular morphology in a modern human population, confirming in part the statement that "large teeth necessitate large jaws."

Interferon regulatory factor 6 variants affect nasolabial morphology in East Asian populations.

OBJECTIVE: The interferon regulatory factor 6 gene (IRF6) is one of the most conspicuous genes among a large number of candidate risk genes for non-syndromic cleft lip with or without cleft palate, which is considered to be a multifactorial defect. Variants of IRF6 are also suggested to affect normal craniofacial variations, especially in the area of the nose and the upper lip. In the present study, we used lateral cephalograms to establish the relationship between IRF6 and sagittal nasolabial morphology in healthy East Asian subjects. DESIGN: Genomic DNA was extracted from 215 Japanese and 226 Korean individuals, and genotyped for five IRF6 single nucleotide polymorphisms (SNPs): rs17389541, rs642961, rs2013162, rs2235371, and rs7802. These SNPs were tested by multiple regression analyses for their association with craniofacial measurements obtained from lateral cephalometrics. RESULTS: We detected a significant association between the derived variants, rs2013162 and rs2235371 and the distances between a facial bone plane indicated by distance from Nasion and Point A (NA plane) to soft tissue landmarks; the Subalare (NA-Sbal) and the Subnasale (NA-Sn) in the sagittal plane. CONCLUSION: Our results indicate that IRF6 variants play an important role in the normal range of variation in nasolabial soft-tissue morphology.

Contribution of FGFR1 Variants to Craniofacial Variations in East Asians.

FGFR1 plays an important role in the development of the nervous system as well as the regulation of the skeletal development and bone homeostasis. Mutations in FGFR1 genes affect skull development, specifically suture and synchondrosis, resulting in craniosynostosis and facial abnormalities. We examined subjects with normal skull morphology for genetic polymorphisms that might be associated with normal craniofacial variations. Genomic DNA was obtained from 216 Japanese and 227 Korean subjects. Four FGFR1 SNPs, namely, rs881301, rs6996321, rs4647905, and rs13317, were genotyped. These SNPs were tested for association with craniofacial measurements obtained from lateral and posteroanterior cephalometries, in which principle component analysis was performed to compress the data of the craniofacial measurements. We observed that SNPs rs13317 and rs6996321 were correlated with the overall head size and midfacial development, indicating that FGFR1 SNPs played crucial roles in the normal variation of human craniofacial morphology. Subjects with the derived alleles of SNPs rs13317 and rs6996321 had a small face and a facial pattern associated with a retruded midface and relatively wide-set eyes. These facial features were similar to but were milder than those of individuals with Pfeiffer syndrome, which is caused by a dysfunctional mutation in FGFR1.

Growth hormone receptor gene variant and three-dimensional mandibular morphology.

OBJECTIVE: To examine the relationship between three-dimensional mandibular morphology and growth hormone receptor (GHR) gene variants in a healthy Japanese population. MATERIALS AND METHODS: The subjects, who were unrelated Japanese orthodontic patients, consisted of 64 men and 114 women. Using the Taqman genotyping assay, GHR gene rs6184 and rs6180 variants were detected in genomic DNA extracted from saliva. Mandibular volume and length were measured from cone-beam computed tomography images that were analyzed using Analyze image-processing software. The relationship between GHR gene variants and three-dimensional mandibular morphology was statistically examined. RESULTS: Statistical significance for the relationship between the distance between the left and right coronoid processes and rs6180 was noted (P < .05). CONCLUSION: Our results indicate that the GHR variant rs6180 is associated with the distance between the left and right coronoid process in the Japanese subjects.

Evaluation of mandibular volume classified by vertical skeletal dimensions with cone-beam computed tomography.

OBJECTIVE: To investigate the relationship between anteroposterior and vertical differences in maxillofacial morphology and mandibular volume. MATERIALS AND METHODS: Subjects comprised 213 Japanese adults (84 males and 129 females) who were divided into three groups based on mandibular basal arch (ANB) and Wits, measured in a cephalometric analysis: Class I (-1° ≤ ANB < 4°,-1 mm ≤ Wits < 0 mm), Class II (ANB ≥ 4°, Wits ≥ 0), and Class III (ANB <-1°, Wits <-1 mm). Subjects were also divided into three groups based on the mandibular plane angle (Mp), as follows: hypodivergent (Mp < 23°), normodivergent (Mp  =  23-30°), and hyperdivergent (Mp > 30°) groups. Mandibular volume was measured from cone-beam computed tomographic images that were analyzed using Analyze™ image processing software and compared among the three groups in each classification. RESULTS: No significant differences were noted in mandibular volume among Classes I, II, and III. An inverse relationship was found between mandibular volume and Mp, and a significant difference was noted in mandibular volume between the hypodivergent and hyperdivergent groups. CONCLUSIONS: In addition to two-dimensional analysis, such as lateral cephalometry, three-dimensional information such as volume, provided by cone-beam computed tomography, contributes to a more detailed assessment of maxillofacial morphology.