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 P561T and C422F polymorphisms in growth hormone receptor gene and mandibular prognathism

Objective:To evaluate the allele and genotype frequencies of the P561T and C422F polymorphic sites of the growth hormone receptor (GHR) gene and the relationship between mandibular prognathism (MP) and these two single-nucleotide polymorphisms (SNPs).Materials and Methods:A total of 99 subjects with severe skeletal Class III MP who planned to undergo orthognathic surgery and 99 subjects with Class I occlusion were examined in this study to evaluate the relationship between MP and two SNPs in exon 10 of the GHR gene. GHR was chosen as a candidate gene because growth hormone plays an important role in cartilage growth. A blood sample was used to extract genomic DNA, and the polymerase chain reaction–restriction fragment length polymorphism method was used to determine genotypes of P561T and C422F. The Minitab 14.0 packet program was used to perform statistical analysis.Results:Allele frequencies of the C422F and P561T variants were determined. Because of the low allele frequency of the control group, statistical analysis could not be performed to test the difference between MP and control groups. Therefore, the data were combined to determine the association between the P561T polymorphism and craniofacial measurements. Effective mandibular length (condylion-gnathion) and lower face height (anterior nasal spina-menton) were associated with the P561T variant.Conclusion:This finding supports that the GHR might be a candidate gene for mandibular morphogenesis in this population.     

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

ObjectiveThe 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.DesignGenomic 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.ResultsWe 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.ConclusionOur results indicate that IRF6 variants play an important role in the normal range of variation in nasolabial soft-tissue morphology.     

Long-term follow-up of intersegmental displacement after orthognathic surgery using cone-beam computed tomographic superimposition

ObjectivesTo evaluate intersegmental displacement during long-term follow-up after bilateral sagittal split osteotomy (BSSO) by mandibular body area superimposition.Materials and MethodsCone-beam computed tomography (CBCT) images of 23 patients ages 18−37 years with class III malocclusion before orthognathic surgery were obtained. A three-dimensional (3D) CBCT examination was performed at four stages: surgery (T0), 6 months after surgery (T1), 1 year after surgery (T2), and long-term follow-up (6.1 ± 2.1 years, T3). The CBCT datasets were superimposed on the symphyseal area and the lower part of the distal segment of the mandible between T0 and the other time points (T1, T2, and T3). The reference points (both condyle, coronoid, and sigmoid) were estimated by the CBCT analyzed program.ResultsThe coronoid, condylion, and sigmoid showed changes within 6 months after surgery, but there was no significant change in the intersegmental displacement between 6 months and 6 years after surgery. The distances between the left and right coronoid, condylion, and sigmoid from T0 to T3 were noted.ConclusionsThe change in intersegmental displacement between T0 and T3 affecting relapse after orthognathic surgery was not significantly different. This suggests that the mandible itself may have a stable morphology during the follow-up period.     

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.”     

Three-dimensional analysis of mandibular functional units in adult patients with unilateral posterior crossbite: A cone beam study with the use of mirroring and surface-to-surface matching techniques

Objectives:To use three-dimensional (3D) mirroring and surface-to-surface techniques to determine any differences in mandibular functional unit shape and morphology between the crossbite side and non-crossbite side in adult patients with posterior unilateral crossbite who had not received any corrective treatment for malocclusion.Materials and Methods:Cone-beam computed tomography (CBCT) records from 24 consecutive adult white patients (mean age, 27.5 years; range 22.6–39.7 years; 14 women and 10 men) seeking treatment for maxillary transverse deficiency were assessed in this study. The control group comprised CBCT scans from age- and sex-matched patients. Segmentation masks were generated to obtain 3D surface mesh models of the mandibles and analyze the six skeletal functional units, which were further analyzed with reverse engineering software.Results:Statistically significant differences in the mean surface distance when comparing the study sample and the control sample were found at the condylar process, mandibular ramus, angular process (P ≤ .0001), and alveolar process (P ≤ .01); no statistically significant differences were found for the coronoid process, the chin, and the mandibular body (P ≥ .5).Conclusions:The condylar, angular, and alveolar processes plus the mandibular ramus appear to play a more dominant role than did the body, the coronoid, and the chin units in the asymmetry of the mandible in patients with unilateral crossbite.     

Evaluation of mandibular volume using cone-beam computed tomography and correlation with cephalometric values

Objective:To investigate the association between maxillofacial morphology and mandibular bone volume in patients with skeletal malocclusion.Materials and Methods:Subjects were 118 adult Japanese (58 males and 60 females). Skeletal malocclusion was classified, based on cephalometric analysis, into skeletal Classes I (−1° ≤ ANB < 4°), II (ANB ≥ 4°), and III (ANB < −1°). Using cone-beam computed tomography and three-dimensional image analysis software, the dental crowns and mandible were separated, with only the mandible extracted. This was then reconstructed as a three-dimensional model, from which the mandibular volume was measured.Results:No significant difference in mandibular volume was noted among skeletal Classes I, II, and III, nor was there any significant correlation between mandibular volume and the ANB, SNB, or mandibular plane angles. There was occasional and limited correlation between mandible volume and gonial angle and certain cephalometric distance parameters.Conclusion:We conclude that proper understanding of the three-dimensional maxillofacial morphology requires not only cephalometric radiographic tracings but also high-resolution analysis of the mandibular area, width, and volume.     

Growth hormone receptor gene variant and mandibular height in the normal Japanese population

This study was aimed at quantitatively evaluating the relationship between craniofacial morphology and the Pro561Thr (P56IT) variant in the growth hormone receptor gene (GHR), which is considered to be an important factor in craniofacial and skeletal growth. The subjects were unrelated individuals in a normal Japanese population and consisted of 50 men and 50 women. With the use of genomic DNA extracted from whole blood, the GHR gene P56IT variant was detected by the polymerase chain reaction-restriction fragment length polymorphism method (with the restriction enzyme StuI). The relationships of the genotypes to body height and 5 linear measurements from lateral cephalograms were examined for evaluation of craniofacial morphology. The normal Japanese population without P56IT had a significantly greater mandibular ramus length (condylion-gonion) than did those with P56IT. This suggests that the GHR gene P56IT variant may be associated with mandibular height growth and can be a genetic marker for it. Further studies about such genetic markers may expand our understanding of the genetic control in craniofacial morphological determinants and help in the prediction of craniofacial growth.     

Alteration of the angle of the coronoid process in prognathism

Muscles and bones may dynamically affect the functions of each other, resulting in changes in the activity of the muscle and/or morphological change in the bones. However, alterations of the morphology of the coronoid process have not been documented in relation to the temporal muscle between the mandible and the cranium. Angles of the coronoid process to the line through the right and the left frontotemporale were measured on posteroanterior (PA) cephalograms in patients with normal occlusions and Class II, division 1 malocclusions, and those with true skeletal Class III malocclusions. Standard deviation of the angle of the coronoid process in patients with Class III malocclusions was greater than those subjects with normal occlusion or Class II, division 1 malocclusions. Differences of angles between the right and the left coronoid process in each patient of either sex were significantly large in true skeletal Class III malocclusions (both P < 0.001). Large variation of angle of the coronoid process was related to prognathism, and this effect may represent adaptation of temporal muscle function to a variety of alterations in mandibular morphology.     

Exploration of genetic factors determining cleft side in a pair of monozygotic twins with mirror-image cleft lip and palate using whole-genome sequencing and comparison of craniofacial morphology

ObjectiveThe aim of the present study is to explore genetic factors determining difference of cleft side using whole-genome sequencing and evaluation of craniofacial morphology using cephalometric analysis between Japanese monozygotic (MZ) twins with mirror-image cleft lip and palate (CLP).DesignWe selected a Japanese MZ twin pair (MZ-A and MZ-B) affected with unilateral CLP who are discordant for cleft side (left/right) and conducted whole-genome sequencing to identify genetic factors determining cleft side. Moreover, we compared their craniofacial morphologies using cephalograms.ResultsWhole-genome sequencing results suggested that no discordant DNA variants were found between MZ-A and MZ-B. The comparison of craniofacial morphology between the MZ twins revealed that MZ-B had maxillary deficiency and slightly more mandibular protrusion than MZ-A.ConclusionsIt is indicated that environmental factors might be a critical factor that influences the determination of difference of cleft side in orofacial clefts. In addition, we found some differences in craniofacial morphology between MZ-A and MZ-B. Our findings suggest that various environmental factors, such as epigenetics, might be a critical factor that influences the determination of difference of cleft side in CLP rather than inherited genetic factors.     

Phenotypes of CCAAT/enhancer‐binding protein beta deficiency: hyperdontia and elongated coronoid process

Oral Diseases (2012) Objectives: This investigation aimed to conduct a case–control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer‐binding protein beta (CEBPB). Materials and methods: Skulls of CEBPB^?/?, CEBPB^+/? and CEBPB^+/+ mice were inspected with micro‐computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. Results: Elongation of the coronoid process was identified in CEBPB^+/? (P ≤ 0.046) and CEBPB^?/? 12‐month‐olds (P ≤ 0.028) but not in 14‐day‐olds (P ≥ 0.217) and 0‐day‐olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB^?/? adult mice was demonstrated (χ² = 6.00, df = 1, P = 0.014). Conclusions: CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed.     

Changes in the buccolingual inclination of first molars with growth in untreated subjects: A longitudinal study

Objectives:To assess longitudinal changes in the buccolingual inclination of the maxillary and mandibular first molars in untreated male and female subjects.Materials and Methods:Forty-seven male and 48 female subjects whose longitudinal dental casts were available at ages 6–16 years, with normal maxillary and mandibular arch forms were included. The original casts at ages 6, 7, 8, 9, 10, 12, 14, and 16 years were digitized and standardized. Measurements were recorded as the differences in cusp heights in the vertical dimension for the mandibular and maxillary first molars using OrthoInsight software.Results:On average, for boys from age 6 to 16 years, both maxillary and mandibular first molars uprighted with age. Maxillary molars uprighted 0.403 mm on the left and 0.418 mm on the right; mandibular molars uprighted 0.441 mm on the left and 0.589 mm on the right. Similarly, for girls from age 6 to 16, both maxillary and mandibular molars uprighted with age. Maxillary molars uprighted 0.67 mm on the left and 0.574 mm on the right; mandibular molars uprighted 0.358 mm on the left and 0.329 mm on the right.Conclusions:Maxillary molars erupted with buccal crown inclination at age 6 in both boys and girls and uprighted lingually with growth. At age 16, maxillary molars were not completely upright but rather maintained some buccal crown inclination. Mandibular molars erupted with lingual crown inclination at age 6 and uprighted buccally with age. At age 16, mandibular molars were not completely upright but rather maintained some lingual inclination.     

Evaluation of median mandibular flexure values in dentulous and edentulous subjects by using an intraoral digital scanner

PURPOSEMandibular flexure is a crucial phenomenon that may affect the success of rigid bilateral mandibular prosthetic treatment. The aim of this study was to determine the amount of median mandibular flexure (MMF) that occurs during mouth opening from anterior to posterior mandible in seven different regions, in different age and gender groups of both dentulous and edentulous subjects, using an intraoral digital scanner.MATERIALS AND METHODSIn this study, the mandibular arch of 56 dentulous and 35 edentulous individuals were scanned with an intraoral scanner at both the minimum mouth opening (MnMO) and the maximum mouth opening (MxMO). MMF values were calculated by subtracting the distance value at the MxMO from the distance between the reference points at the MnMO at seven different mandibular regions of dentulous and edentulous subjects. In addition, the left and right side MMF values were measured. All data were analyzed statistically (α = .05).RESULTSMMF value increased linearly from anterior to posterior mandible in both dentulous and edentulous individuals. The differences in MMF values were not statistically significant according to side (left/right), age, or gender (P > .05). No significant differences were found between the mean MMF values of the same region in both dentulous and edentulous individuals (P > .05).CONCLUSIONMMF was seen in different regions of the mandibles of both edentulous and dentulous individuals measured at the MxMO. Mandibular flexure should be considered for the success and prognosis of the long-span and rigid prostheses.     

Accuracy of three-dimensional dental resin models created by fused deposition modeling,stereolithography, and Polyjet prototype technologies: A comparative study

Objectives: The aim of this study was to assess the dimensional accuracy of fused deposition modeling (FDM)–, Polyjet-, and stereolithography (SLA)–produced models by comparing them to traditional plaster casts.Materials andMethods: A total of 12 maxillary and mandibular posttreatment orthodontic plaster casts were selected from the archives of the Orthodontic Department at the Indiana University School of Dentistry. Plaster models were scanned, saved as stereolithography files, and printed as physical models using three different three-dimensional (3D) printers: Makerbot Replicator (FDM), 3D Systems SLA 6000 (SLA), and Objet Eden500V (Polyjet). A digital caliper was used to obtain measurements on the original plaster models as well as on the printed resin models.Results: Comparison between the 3D printed models and the plaster casts showed no statistically significant differences in most of the parameters. However, FDM was significantly higher on average than were plaster casts in maxillary left mixed plane (MxL-MP) and mandibular intermolar width (Md-IMW). Polyjet was significantly higher on average than were plaster casts in maxillary intercanine width (Mx-ICW), mandibular intercanine width (Md-ICW), and mandibular left mixed plane (MdL-MP). Polyjet was significantly lower on average than were plaster casts in maxillary right vertical plane (MxR-vertical), maxillary left vertical plane (MxL-vertical), mandibular right anteroposterior plane (MdR-AP), mandibular right vertical plane (MdR-vertical), and mandibular left vertical plane (MdL-vertical). SLA was significantly higher on average than were plaster casts in MxL-MP, Md-ICW, and overbite. SLA was significantly lower on average than were plaster casts in MdR-vertical and MdL-vertical.Conclusions: Dental models reconstructed by FDM technology had the fewest dimensional measurement differences compared to plaster models.     

Three-dimensional analysis of upper airway morphology in skeletal Class III patients with and without mandibular asymmetry

Objective:To compare the three-dimensional (3D) morphology of the upper airway in skeletal Class III patients with and without mandibular asymmetry and to investigate the possible underlying correlations between the morphology of the upper airway and mandibular deviation.Materials and Methods:Cone-beam computed tomography images of 54 subjects with skeletal Class III malocclusion (ANB angle ≤ 0.4°, Wits ≤ −5.5°) were taken and 3D upper airway models were reconstructed using Dolphin 3D software. According to the distance (d) from symphysis menti to the sagittal plane, all subjects were divided into a symmetry group (d ≤ 2 mm) and an asymmetry group (d ≥ 4 mm). Based on the severity of mandibular deviation, the asymmetry group was divided into subgroup I (4 mm ≤d <10 mm) and subgroup II (d ≥ 10 mm). Cross-sectional linear distances, areas, and volumetric variables of the upper airway were measured in the 3D airway model.Results:Width of the inferior limit of the glossopharynx (P3W), cross-sectional area of the anterior limit of the nasal airway (P5S), and height of the glossopharynx (GPH) in the asymmetry group were significantly larger than in the symmetry group. As for subjects with severe mandibular deviation in subgroup II (d ≥ 10 mm), volume of the glossopharynx (GPV), total volume of the pharynx (TPV), length of the inferior limit of the velopharynx (P2L), and ratio of length to width of the inferior limit of the velopharynx (P2L/P2W) showed significantly negative correlations with mandibular deviation (r > 0.7, P < .05).Conclusions:In Class III subjects with severe mandibular asymmetry, the pharyngeal airway showed a tendency toward constriction and presented a more elliptical shape as mandibular deviation became more severe (P < .01).     

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.     

The growth hormone receptor gene is associated with mandibular height in a Chinese population

Genetic influences are important in the determination of mandibular morphology, and growth hormone receptor (GHR) is believed to have an important influence on the growth of craniofacial bone. In this study, we used quantitative trait locus methods to evaluate the relationship between craniofacial morphology and single-nucleotide polymorphisms (SNPs) in GHR in an unselected healthy Chinese population. We systematically screened the 10 exons and nearby introns of GHR and identified 6 SNPs. Using 4 SNPs as markers, we studied the relationships between genotypes and craniofacial linear measurements. Individuals with the genotype CC of polymorphism I526L had a significantly greater mandibular ramus length (condylion-gonion/ articulare-gonion) than those with genotype AC or AA. Haplotype analysis showed that there were also significant differences between the long and short mandibular height groups in an extreme population. Our results indicate that the GHR gene polymorphism I526L is associated with mandibular height in the Chinese population.     

Iperplasia bilaterale del processo coronoideo in pazienti pediatrici

ObjectivesTo present an international literature review on the coronoid hyperplasia in pediatric patients, describing the etiology, the diagnosis and the therapeutic options.Materials and methodsA systematic revision of the international literature has been done on Medline database (www.ncbi.nlm.nih.gov/pubmed). Keywords chosen were: “bilateral coronoid hyperplasia”, “coronoid process”, “temporomandibular joint ankylosis”, “coronoid hyperplasia and treatment”, “pediatric patients”.ResultsAmong the pathogenetic factors, there are: temporalis muscle hyperactivity, genetic inheritance, hormonal stimulus, temporomandibular joint dysfunctions, traumas and persistent coronoid cartilage growth centre. The main symptoms are: mandibular hypomobility, alterations in protrusion and in lateral mandibular movements and muscular dystonia. Orthopantomography, magnetic resonance imaging and computed tomography are the diagnostic gold standards. The most widely surgical treatment used is coronoidectomy.ConclusionsOn the scientific evidences present in literature it's possible to conclude that, being coronoid hyperplasia a frequent pediatric condition, an early diagnosis is important to restore stomatognathic multifunctions as soon as possible.     

Laterality of Asymmetry in Movements of the Corners of the Mouth during Voluntary Smile

Objectives:To examine (1) the laterality of asymmetry in movements of the right and left corners of the mouth in space during voluntary smile and (2) the laterality of asymmetry in relation to the difference between the right and left hemiface size and the handedness.Materials and Methods:Participants were 155 volunteer Japanese female adults. They were categorized into the symmetric group (n  =  120) and the right-side hemiface dominant group (n  =  26) according to the hemiface size. In addition, the symmetric group was categorized into the right-handed group (n  =  98) and the left-handed group (n  =  22) according to the Edinburgh Handedness Inventory. Position vectors of the right and left corners of the mouth were obtained from the three-dimensional facial images for the rest, the maximal lip corner retraction, and the portrait smile. The displacements of the right and left corners of the mouth for each expression and the proportions of the subjects with the right- and left-sided laterality were compared.Results:The left corner of the mouth showed significantly greater displacement (P < .01) than the right in the symmetric group for the portrait smile. The left-sided laterality was found regardless of the handedness.Conclusions:Displacements of the right and left corners of the mouth during voluntary smile were asymmetric, and the left-sided laterality was found. Also, the laterality of the facedness differed in relation to the hemiface size, but was not related to the handedness.