Introduction Botulinum toxin type A causes muscle paralysis and is widely used in the masticatory muscle for stomatognathic diseases, such as temporomandibular disorder, bruxism, or masseteric hypertrophy. Nonetheless, its muscular effect remains unclear. Better understanding could aid improved use and perhaps new indications, particularly in dentofacial orthopaedics and orthognathic surgery. Methods This systematic review explored the histologic and functional effects of botulinum toxin in animal and human masticatory muscles and was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The MEDLINE, Web of Science, and Cochrane Library electronic databases were searched for relevant articles. The inclusion criteria were human or animal masticatory muscle analysis after botulinum toxin injection(s) AND histological structural/ultrastructural analysis by optical or electronic microscopy OR functional effect analysis by bite force evaluation (occlusal force analyzer) and muscle activity (electromyography). Results Of an initial 1578 articles, 44 studies were eventually included. Botulinum toxin injection in the masticatory muscle altered its histological structure and functional properties. The human and animal studies revealed ultrastructural change, atrophy, and fiber type modifications of the masticatory muscles after one injection. Botulinum toxin decreased bite force and muscle activity, but recovery was uncertain. Conclusions Muscle forces applied on the skeleton is a key feature of facial growth. Masticatory muscle paralysis changes mechanical stress on bones, which rebalances the force applied on facial bones. This new balance could benefit dental deformity or surgical relapse. Therefore, botulinum toxin could limit the orthognathic effect of the masticatory muscles in such patients. Given the uncertain recovery, multiple injections should be avoided, and usage should not deviate from established consensus.

Objectives Main aim of the study was to explore the association between genetic polymorphisms in ACTN3 and bruxism. Secondary objectives included masseter muscle phenotypes assessment between bruxers and non-bruxers and according to genetic polymorphisms in ACTN3. Materials and Methods Fifty-four patients undergoing orthognathic surgery for correction of their malocclusion were enrolled. Self-reported bruxism and temporomandibular disorders status were preoperatively recorded. Saliva samples were used for ACTN3 genotyping. Masseter muscle samples were collected bilaterally at the time of orthognathic surgery to explore the muscle fiber characteristics. Results There were significant differences in genotypes for rs1815739 (R577X nonsense) (p = 0.001), rs1671064 (Q523R missense) (p = 0.005), and rs678397 (intronic variant) (p = 0.001) between bruxers and non-bruxers. Patients with self-reported bruxism presented a larger mean fiber area for types IIA (p = 0.035). The mean fiber areas in individuals with the wild-type CC genotype for rs1815739 (R577X) were significantly larger for type IIA fibers (1394.33 mu m(2) [572.77 mu m(2)]) than in those with the TC and TT genotypes (832.61 mu m(2) [602.43 mu m(2)] and 526.58 mu m(2) [432.21 mu m(2)] [p = 0.014]). Similar results for Q523R missense and intronic variants. Conclusions ACTN3 genotypes influence self-reported bruxism in patients with dentofacial deformity through specific masseter muscle fiber characteristics.

Oral DiseasesEarly View LETTER TO THE EDITOR Response to “sleep bruxism, wake bruxism, or both? The importance of their full reporting and diagnosis” Romain Nicot, Corresponding Author Romain Nicot romain.nicot@gmail.com orcid.org/0000-0001-7391-2121 Department of Oral and Maxillofacial Surgery, Roger Salengro Hospital, Univ. Lille, Inserm, CHU Lille, Lille, France Correspondence Romain Nicot, Service de Chirurgie Maxillo Faciale et Stomatologie Hôpital Roger Salengro, Bd du Prof Emile Laine, 59037 Lille Cedex, France. Email: romain.nicot@gmail.com Contribution: Formal analysis, ​Investigation, Validation, Writing - original draftSearch for more papers by this authorGwénaël Raoul, Gwénaël Raoul Department of Oral and Maxillofacial Surgery, Roger Salengro Hospital, Univ. Lille, Inserm, CHU Lille, Lille, France Contribution: Formal analysis, Supervision, Validation, Writing - review & editingSearch for more papers by this authorJames J. Sciote, James J. Sciote Department of Orthodontics, Temple University, Philadelphia, Pennsylvania, USA Contribution: Formal analysis, Project administration, Supervision, Validation, Writing - review & editingSearch for more papers by this author Romain Nicot, Corresponding Author Romain Nicot romain.nicot@gmail.com orcid.org/0000-0001-7391-2121 Department of Oral and Maxillofacial Surgery, Roger Salengro Hospital, Univ. Lille, Inserm, CHU Lille, Lille, France Correspondence Romain Nicot, Service de Chirurgie Maxillo Faciale et Stomatologie Hôpital Roger Salengro, Bd du Prof Emile Laine, 59037 Lille Cedex, France. Email: romain.nicot@gmail.com Contribution: Formal analysis, ​Investigation, Validation, Writing - original draftSearch for more papers by this authorGwénaël Raoul, Gwénaël Raoul Department of Oral and Maxillofacial Surgery, Roger Salengro Hospital, Univ. Lille, Inserm, CHU Lille, Lille, France Contribution: Formal analysis, Supervision, Validation, Writing - review & editingSearch for more papers by this authorJames J. Sciote, James J. Sciote Department of Orthodontics, Temple University, Philadelphia, Pennsylvania, USA Contribution: Formal analysis, Project administration, Supervision, Validation, Writing - review & editingSearch for more papers by this author First published: 04 August 2022 https://doi.org/10.1111/odi.14334Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Objective: To assess longitudinal variation in patterns of retromolar space growth, with regard to sex and cervical vertebrae maturation.Design: We utilized serial lateral cephalograms from three craniofacial growth studies (Denver, Iowa, Oregon), measuring retromolar space and cervical vertebrae maturation in 99 subjects (56% male) from 8 to 18 years of age for each subject. Repeated measures ANOVA and a linear mixed effects model were used to assess retromolar space growth through time.Results: Our analyses revealed an average increase in retromolar space of 8.73 mm from 8 to 18 years. While t -tests failed to find differences in retromolar space growth between males and females at the measured age points, repeated measures ANOVA and linear mixed effects models revealed modest differences in growth trends be-tween sexes, with females having more growth earlier but a younger age of deceleration of growth (between 12 and 14 years of age).Conclusions: Our results confirm large increases in retromolar space through growth, reaching an average of 1.38 mm/year around puberty. Importantly, we add to the conversation regarding sex differences, showing differ-ences in timing of growth. This highlights the importance of using longitudinal data and analytical approaches to address questions of this nature.

INTRODUCTION Cranio-Maxillofacial Dysplasias (CMD), including Craniofacial Microsomias, syndromes (such as Treacher Collins or Williams) and isolated Condylo-Mandibulo-Dysplasia, is a controversial subject with treatments as diverse as diagnostic classifications. The authors present here a retrospective study of 85 patients, with congenital condyle dysplasia arising from these 3 main types of CMD, treated with different techniques that aimed to normalize the facial skeleton and occlusion. METHODS The authors studied retrospectively 85 patients, aged from 3 to 53 years old, affected by different types of CMD. Treatment options included: costochondral grafts, orthognathic surgeries, distraction osteogenesis procedures, orthodontic and dentofacial orthopedic treatments, and soft tissues surgeries. Outcomes were evaluated by the surgical team. RESULTS Seventeen patients were treated with costochondral grafting, 14 with distraction osteogenesis, 17 with orthodontic and dentofacial orthopedic, and 45 with orthognathic surgery. The authors did not perform any nerve grafting or temporomandibular joints prosthesis placement. Fifty-one patients presented an excellent result, 10 a good result, 9 a poor result, 2 a bad result, and 14 an unknown result. DISCUSSION Several different treatments of CMD can be proposed. The authors think that major defect in children should undergo costochondral grafting because of its growth potential while in case of minor defect, orthopedic treatment should be tried in the first place. Distraction osteogenesis should be reserved for cases with poor response after orthopedic treatment or growth insufficiency with costochondral grafting. Orthognathic surgery is often necessary at the end of the growth period to obtain an excellent result. Temporomandibular joints prosthesis should be reserved for extreme cases.

Craniofacial asymmetry, mandibular condylar modeling and temporomandibular joint disorders are common comorbidities of skeletally disproportionate malocclusions, but etiology of occurrence together is poorly understood. We compared asymmetry, condyle modeling stability and temporomandibular health in a cohort of 128 patients having orthodontics and orthognathic surgery to correct dentofacial deformity malocclusions. We also compared ACTN3 and ENPP1 genotypes for association to clinical conditions. Pre-surgical posterior-anterior cephalometric and panometric radiographic analyses; jaw pain and function questionnaire and clinical examination of TMD; and SNP-genotype analysis from saliva samples were compared to assess interrelationships. Almost half had asymmetries in need of surgical correction, which could be subdivided into four distinct morphological patterns. Asymmetric condyle modeling between sides was significantly greater in craniofacial asymmetry, but most commonly had an unanticipated pattern. Often, longer or larger condyles occurred on the shorter mandibular ramus side. Subjects with longer ramus but dimensionally smaller condyles were more likely to have self-reported TMD symptoms (p = 0.023) and significantly greater clinical diagnosis of TMD (p = 0 .000001), with masticatory myalgia most prominent. Genotyping found two significant genotype associations for ACTN3 rs1671064 (Q523R missense) p = 0.02; rs678397 (intronic SNP) p = 0.04 and one significant allele association rs1815739 (R577X nonsense) p = 0.00. Skeletal asymmetry, unusual condyle modeling and TMD are common and interrelated components of many dentofacial deformities. Imbalanced musculoskeletal functional adaptations and genetic or epigenetic influences contribute to the etiology, and require further investigation.

Objectives: Bilateral sagittal split osteotomy (BSSO) is a morpho-functional surgery and post-surgical osteosynthesis may influence temporomandibular joint (TMJ) health. Our objective was to evaluate temporomandibular disorders (TMD) and TMJ symptoms after orthognathic surgery according to the type of osteosynthesis used in a population of patients with dentofacial deformities. Materials and methods: One hundred and eighty-three consecutive patients undergoing orthodontic and maxillofacial surgery treatment for correction of their malocclusion were recruited for a two-year period at Lille University Hospital. All patients had at least a mandibular BSSO using Epker's technique. Each patient was examined before and one year after orthognathic surgery. We compared osteosynthesis by miniplates fixed with monocortical screws (n = 42) and the hybrid fixation with bicortical retro-molar screws used with miniplates (n = 141). TMJ health was assessed by monitoring TMD signs and symptoms according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and scores obtained from the "Jaw Pain Function" questionnaire. Results: There was no significant difference in pre-operative and one year post-operative RDC/TMD assessments (p >= 0.91) or JPF score (p >= 0.29) between the two types of osteosynthesis. Conclusion: There was no difference in TMJ health between the two techniques of osteosynthesis after BSSO. Clinical relevance: In our experience the hybrid technique fixation affords many advantages and does not influence postoperative TMD compared with osteosynthesis by miniplates. (C) 2020 Elsevier Masson SAS. All rights reserved.

BackgroundTemporomandibular disorders (TMDs) are frequent and disabling, and hence, preventing them is an important health issue. Combining orthodontic and surgical treatments for malocclusions has been shown to affect temporomandibular joint (TMJ) health. However, publications regarding the risk factors that predict negative TMJ outcomes after orthognathic surgery are scarce. ObjectivePresent prospective cohort study was conducted to identify an association between pre-operative dysfunctional/parafunctional oral habits and the presence of TMD symptoms after orthognathic surgery. MethodWe included 237 patients undergoing orthodontics and surgical treatment for malocclusions associated with dentofacial deformities within the Department of Oral and Maxillofacial Surgery of the University of Lille. Their parafunctional and dysfunctional oral habits were recorded through clinical examination along with the presence of TMD symptoms before and after the surgery. According to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) classification, the TMD symptoms studied were myalgia, arthralgia, disc displacement with or without reduction. ResultsMultivariate analysis revealed significant associations among bruxism (odds ratio [OR] 3.17 [1.066; 9.432]), lingual interposition (OR 4.241 [1.351; 13.313]), as well as primary swallowing (OR 3.54 [1.225; 10.234]) and the presence of postoperative symptoms of myalgia. Moreover, a significant association was observed between the presence of any dysfunctional oral habit and postoperative disc displacement with reduction (OR 4.611 [1.249; 17.021]). ConclusionBruxism and dysfunctional oral habits were shown to be risk factors for the presence of TMD symptoms also after combined orthodontic and surgical treatment. Treating such habits before orthognathic surgery should help prevent TMD.

PURPOSE:Bone remodeling is essential in maintaining bone health. Considering that ENPP1 contributes to bone geometry and bone mineralization, the aim of our study was to analyze the association between single-nucleotide polymorphisms (SNPs) of ENPP1 and condylar remodeling.MATERIALS AND METHODS:A total of 156 patients undergoing orthodontic and maxillofacial surgery treatment for correction of malocclusion were included in this prospective study. Saliva samples from all subjects were used for DNA extraction and genotyping. Four ENPP1 SNPs were selected and tested to determine whether specific allelic variants are correlated with condylar remodeling. The criteria of condylar remodeling chosen were the ratio between each side of condylar height or surface differences on a dental panoramic of each patient. A diagnostic threshold was set at 15% difference between both sides.RESULTS:The ENPP1 SNP rs9373000 showed a statistically significant association with condylar height ratio >15% (p = 0.012). The GG genotype was found to be a protective factor against condylar height decrease (p = 0.003).CONCLUSION:This study identifies the genetic variant rs9373000 as a potentially causal variant for mandibular condyle geometry variation for patients presenting with dento-facial deformities.

Introduction: We investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment. Methods: One hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanterior cephalometric measurements. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD. Results: Fifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (P = 0.004), and rs858339 was associated with group 3 (P = 0.002). ESR1 SNP-rs164321 was associated with group 4 (P = 0.019). These results were confirmed by principal component analysis that showed 3 principal components explaining almost 80% of the variations in the studied groups. Principal components 1 and 2 were associated with ESR1 SNP-rs3020318 (P <0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1 year after treatment. Conclusions: Posteroanterior cephalometrics can classify asymmetry into distinct groups and identify the probability of TMD and genotype associations. Orthodontic and orthognathic treatments of facial asymmetry are effective at eliminating TMD in most patients.

Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment.Perspective: This study allows us to identify sub-populations at high risk of developing postoperative temporomandibular disorders after orthognathic surgery procedures. Many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort. (C) 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Purpose Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes that are down-regulated in patients with facial asymmetry. Methods Masseter muscle samples were collected during bilateral sagittal split osteotomy orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. Results Overall gene expression was different for asymmetric patients compared with other malocclusion classifications by principal component analysis (P < 0.05). We identified differences in the nodal signaling pathway, which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39- to 1.84-fold greater (P < 3.41 × 10−5), whereas integral membrane Nodal modulators Nomo1,2,3 were −5.63 to −5.81 (P < 3.05 × 10−4) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of −7.02 to −2.47 (P < 0.003). Finally Pitx2, an upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P < 0.05). Conclusions When facial asymmetry is part of skeletal malocclusion, there are decreases in nodal signaling pathway genes in masseter muscle. This data suggest that the nodal signaling pathway is down-regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition.

Objective: Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C, are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodelling epigenetic enzyme which is activated by MYO1C) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B).Design: Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fibre type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan (R) RT-PCR. Fibre type properties, gene expression quantities and malocclusion classification were compared.Results: There were very significant associations (P <0.0000001) between MYO1C and KAT6B expressions. There were also significant associations (P < 0.005) between RUNX2 expression and masseter muscle type II fibre properties. Very few significant associations were identified between MYO1C and masseter muscle fibre type properties.Conclusions: The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodelling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibres, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle. (C) 2014 Elsevier Ltd. All rights reserved.

We have investigated an orthognathic surgery population to determine how variation in masticatory muscle gene expression and genotype plays a key role in development of both jaw-deformation malocclusion and temporomandibular joint disorders (TMD). A gene of particular interest is ACTN3 since the common R577X polymorphism results in α-actinin-3 protein loss, reduced myofiber Z-disc structural integrity in skeletal muscle and decreased osteoblast/osteoclast activity in bone formation. Secondly, since the prevalence of TMD in this population is quite high (30%) we sought to determine if genes related to pain processes─previously identified in the Orofacial Pain: Prospective Evaluation and Risk Assessment Study (OPPERA) were differentially expressed.

Introduction: alpha-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of alpha-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. Methods: Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results: Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P < 0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P = 0.002). Conclusion: ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.

The aim of this work is to review the relationship between the function of the masseter muscle and the occurrence of malocclusions. An analysis was made of the masseter muscle samples from subjects who underwent mandibular osteotomies. The size and proportion of type-II fibers (fast) decreases as facial height increases. Patients with mandibular asymmetry have more type-II fibers on the side of their deviation. The insulin-like growth factor and myostatin are expressed differently depending on the sex and fiber diameter. These differences in the distribution of fiber types and gene expression of this growth factor may be involved in long-term postoperative stability and require additional investigations. Muscle strength and bone length are two genetically determined factors in facial growth. Myosin 1H (MYOH1) is associated with prognathia in Caucasians. As future objectives, we propose to characterize genetic variations using "Genome Wide Association Studies" data and their relationships with malocclusions.

Introduction: Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions. Methods: Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction. Results: Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX. Conclusions: These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.

Introduction: Human masseter muscle fiber type properties associate with variations in vertical growth of the face, highlighting clinically significant relationships between musculoskeletal function and malocclusion. MYO1H is an unconventional myosin whose function is not fully understood, but its paralog MYO1C regulates glucose metabolism and intracellular transport. We have recently determined that a variation in the MYO1H gene associates with mandibular prognathism in Caucasians. To better understand the role MYO1H and MYO1C play in facial growth we examined their gene expression in masseter muscle from dentofacial deformity subjects undergoing surgery for treatment jaw skeleton-based malocclusions.

Introduction: Several candidate loci have been suggested as influencing mandibular prognathism (1p22.1, 1p22.2, 1p36, 3q26.2, 5p13-p12, 6q25, 11q22.2-q22.3, 12q23, 12q13.13, and 19p13.2). The goal of this study was to replicate these results in a well-characterized homogeneous sample set. Methods: Thirty-three single nucleotide polymorphisms spanning all candidate regions were studied in 44 prognathic and 35 Class I subjects from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository. The 44 subjects with mandibular prognathism had an average age of 18.4 years; 31 were female and 13 male; and 24 were white, 15 African American, 2 Hispanic, and 3 Asian. The 36 Class I subjects had an average age of 17.6 years; 27 were female and 9 male; and 27 were white, 6 African American, 1 Hispanic, and 2 Asian. Skeletal mandibular prognathism diagnosis included cephalometric values indicative of Class III such as an ANB smaller than 2 degrees, a negative Wits appraisal, and a positive A-B plane. Additional mandibular prognathism criteria included negative overjet and visually prognathic (concave) profile as determined by the subject's clinical evaluation. Orthognathic subjects without jaw deformations were used as the comparison group. The mandibular prognathic and orthognathic subjects were matched by race, sex, and age. Genetic markers were tested by polymerase chain reaction with TaqMan chemistry. Chi-square and Fisher exact tests were used to determine overrepresentation of marker allele with an alpha of 0.05. Results: An association was unveiled between a marker in MYO1H (rs10850110) and the mandibular prognathism phenotype (P = 0.03). MYO1H is a Class I myosin that is in a different protein group than the myosin isoforms of muscle sarcomeres, which are the basis of skeletal muscle fiber typing. Class I myosins are necessary for cell motility, phagocytosis, and vesicle transport. Conclusions: More strict clinical definitions might increase homogeneity and aid the studies of genetic susceptibility to malocclusions. We provide evidence that MYO1H can contribute to mandibular prognathism. (Am J Orthod Dentofacial Orthop 2012;141:51-9)

Purpose: We identified masseter muscle fiber type property differences in subjects with dentofacial deformities.Patients and Methods: Samples of masseter muscle were collected from 139 young adults during mandibular osteotomy procedures to assess mean fiber areas and percent tissue occupancies for the 4 fiber types that comprise the muscle. Subjects were classified into 1 of 6 malocclusion groups based on the presence of a skeletal Class II or III sagittal dimension malocclusion and either a skeletal open, deep, or normal bite vertical dimension malocclusion. In a subpopulation, relative quantities of the muscle growth factors IGF-I and GDF-8 gene expression were quantified by real-time polymerase chain reaction.Results: Fiber properties were not different in the sagittal malocclusion groups, but were very different in the vertical malocclusion groups (P < .0004). There were significant mean fiber area differences for type II (P <= .0004) and type neonatal-atrial (P = .001) fiber types and for fiber percent occupancy differences for both type I-II hybrid fibers and type II fibers (P <= .0004). Growth factor expression differed by gender for IGF-I (P = .02) and GDF-8 (P < .01). The ratio of IGF-I: GDF-8 expression associates with type I and II mean fiber areas.Conclusion: Fiber type properties are very closely associated with variations in vertical growth of the face, with statistical significance for overall comparisons at P <= .0004. An increase in masseter muscle type II fiber mean fiber areas and percent tissue occupancies is inversely related to increases in vertical facial dimension. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70: 440-448, 2012