Three novel genes tied to mandibular prognathism in eastern Mediterranean families.

INTRODUCTION: Mandibular prognathism (MP) is subject to major polygenic influence and segregates within families in autosomal dominance with variable expressivity and incomplete penetrance. We aimed to identify the inheritance pattern and genes and loci involved in the development of MP in Mediterranean families and to evaluate the dentoskeletal characteristics of affected individuals. METHODS: Fifty-one eastern Mediterranean families with individuals affected by MP were identified. Data and biospecimens were collected from 14 of the families, including clinical examination, lateral cephalography (on subjects with Class III malocclusion), and 5 mL blood drawn from consenting affected and nonaffected relatives. Next-generation sequencing (NGS) was performed on 8 families (7 Lebanese, 1 Lebanese/Syrian), including large numbers of affected individuals over many generations and severe conditions, with the use of whole-exome sequencing. RESULTS: Most pedigrees suggested autosomal-dominant inheritance with an equal number of affected male and female individuals. Affected individuals had macrognathic and prognathic mandibles with dentoalveolar compensation. Genetic screening did not correspond with previously reported MP-linked genes, but yielded 3 novel genes (C1orf167, NBPF8, NBPF9) on chromosome 1 potentially responsible for mandibular development and macrognathism. CONCLUSIONS: In this first genetic study with the use of NGS on the largest reported number of families with MP, novel genes (C1orf167, NBPF8, NBPF9) were associated with familial MP in the eastern Mediterranean population.

The Influential Bony Factors and Vectors for Predicting Soft Tissue Responses After Orthognathic Surgery in Mandibular Prognathism.

PURPOSE: We sought to identify the hard tissue points and vectors that have the greatest effect on soft tissue movement after orthognathic surgery in patients with mandibular prognathism. PATIENTS AND METHODS: The present retrospective study involved patients who had undergone mandibular setback surgery with or without maxillary advancement. Multiple linear regression models were adapted to evaluate the association between the 8 hard tissue landmark (predictor variables) changes and 11 soft tissue responses (outcome variables) using the x and y coordinates assessed from superimposed pre- and postoperative 3-dimensional computed tomography images. RESULTS: A total of 50 patients (42 patients had undergone 2-jaw surgery; 8 patients had undergone 1-jaw surgery; mean age 23 ± 4 years) were included in the present study. Our statistical models demonstrated that the horizontal hard tissue changes had a greater influence on the soft tissue responses than did the vertical changes, and these changes were more notable in the lower facial area (lower lip contour and chin profile) than the midfacial area (nasal profile, upper lip contour, upper lip length, and nasolabial angle). In the horizontal soft tissue response model, the soft tissue A point/A point ratio was 0.86:1 (95% confidence interval [CI] 0.674-1.049); the soft tissue B point/B point ratio was almost 1:1 (95% CI 0.919-1.071); and the soft tissue pogonion/pogonion ratio was 0.88:1 (95% CI 0.805-0.963). CONCLUSIONS: Horizontal or vertical bone tissue changes affected both the horizontal and vertical soft tissue changes in most areas. Our study demonstrated that the soft tissue response is not linear but a more complicated and dynamic reaction.

The main occluding area in normal occlusion and mandibular prognathism.

OBJECTIVE: To clarify whether the concept of main occluding area, where hard food is initially crushed, exists in patients who have a jaw deformity. MATERIALS AND METHODS: Nineteen subjects with normal occlusion, 18 patients with mandibular prognathism, and 11 patients with mandibular prognathism who had undergone orthognathic surgery participated in this study. The main occluding area was identified by clenching Temporary Stopping. The coincidence, location of the main occluding area, and distance from the first molars to main occluding area were examined. RESULTS: High coincidence of the main occluding area was obtained in all groups, signifying that the main occluding area exists even in these patients. Mandibular main occluding area was located on the first molar in all groups. Maxillary main occluding area in subjects with normal occlusion was located on the first molar. However, it was located on the second premolar and first molar in patients with mandibular prognathism, and on the first and second molars in patients with mandibular prognathism who had undergone orthognathic surgery. There was a statistically significant difference in distance from the maxillary first molar to the main occluding area among groups, but there was no difference in the distance from the mandibular first molar among groups. CONCLUSION: The main occluding area is more stable on the mandibular first molar than the maxilla in all groups.

Prenatal sex hormones, digit ratio, and face shape in adult males.

OBJECTIVES: Several reports have demonstrated a relationship between second to fourth digit ratio (2D:4D) and facial shape, suggesting that prenatal sex hormones play a role in the development of the craniofacial complex. Using 3D surface imaging and geometric morphometrics, we test the hypothesis that decreased digit ratio (indicative of increased prenatal androgen exposure) is associated with a more masculine facial phenotype. METHODS: 3D facial surface images and digit measures were collected on a sample of 151 adult males. Facial landmarks collected from the images were aligned by Procrustes superimposition and the resulting shape coordinates regressed on 2D:4D. Variations in facial shape related to 2D:4D were visualized with deformable surface warps. RESULTS: A significant statistical relationship was observed between facial shape variation and 2D:4D (p = 0.0084). Lower 2D:4D ratio in adult males was associated with increased facial width relative to height, increased mandibular prognathism, greater nasal projection, and increased upper and lower lip projection. CONCLUSIONS: A statistical relationship between 2D:4D and facial shape in adult males was observed. Faces tended to look more masculine as 2D:4D decreased, suggesting a biologically plausible link between prenatal androgen exposure and the development of male facial characteristics.

The skeletal stability after maxillo-mandibular osteotomy with a "physiological positioning strategy".

The aim of this study was to estimate skeletal and dental stability after maxillomandibular osteotomy with physiological positioning. Ten patients (7 men and 3 women) with skeletal mandibular prognathism were treated by conventional Le Fort I osteotomy for the maxilla and unfixed short lingual osteotomy for the mandible together with physiological positioning. We used cephalometric analysis to evaluate the skeletal and dental stability preoperatively, immediately after maxillomandibular osteotomy, and more than 1 year later. The immediately postoperative measurements for the SNA and the SN-palatal planes were 0.15° (p=0.67) and 1.0° (p=0.17), respectively. The positions of the anterior nasal spine, posterior nasal spine, and A point showed minimal changes 1 year postoperatively. The postoperative difference for SNB was 0.76° (p=0.04). Dental stability was apparent postoperatively. We conclude that reliable stability of both the maxilla and the mandible was achieved after maxillomandibular osteotomy with physiological positioning in patients with mandibular prognathism.

Relapse after SSRO for mandibular setback movement in relation to the amount of mandibular setback and intraoperative clockwise rotation of the proximal segment.

The aim of this study was to evaluate the effect of the amount of setback movement and intraoperative clockwise rotation of the proximal segments on postoperative stability after orthognathic surgery to correct mandibular prognathism. Thirty-six patients with mandibular prognathism who underwent orthognathic surgery with bilateral sagittal split ramus osteotomy were evaluated. The amount of postoperative relapse was analyzed using a cephalometric analysis. Six months after surgery, the mean backward movement of the mandible at point B was 11.2 mm, the mean intraoperative clockwise rotation of the proximal segment was 4.3° and the amount of postoperative relapse at point B was 2.3 mm (20.3%) on average. The tendency of relapse did not significantly increase with the amount of setback but did increase significantly with the intraoperative clockwise rotation of the proximal segment. This study suggested that postoperative relapse after mandibular setback surgery might be more related to the degree of the intraoperative clockwise movement of the proximal segment, rather than the amount of setback movement. When the amount of mandibular setback is considerable, postoperative relapse might be minimized with adequate control of the intraoperative positioning of the proximal segments.

Contributing factors to intraoperative clockwise rotation of the proximal segment as a relapse factor after mandibular setback with sagittal split ramus osteotomy.

The aims of this study were to analyze possible contributing factors to intraoperative clockwise rotation (CWR) of the proximal segment (PS), which is known to be a primary factor for relapse after mandibular setback with sagittal split ramus osteotomy (SSRO) and to evaluate the correlation between the CWR of the PS and relapse tendency. The sample was comprised of 47 patients who underwent SSRO for mandibular setback. Lateral cephalograms were analyzed. The vertical difference between the inferior borders of the PS and the distal segment at the vertical osteotomy line for SSRO after setback of the distal segment (vertical bony step, VBS) was the most predictable factor for CWR of the PS (p < 0.001), and it correlated significantly with the gonial angle, the surgical change in SNB, and the downward movement of the maxilla (p < 0.05). Patients with large CWR of the PS showed a greater tendency in horizontal relapse than patients with small CWR of the PS (p < 0.05). Such relapse patterns could be prevented with adequate surgical planning designed to reduce the VBS, such as maxillary posterior impaction or the intentional guidance of the PS to maintain the original position of the PS without CWR.

A simple classification of facial asymmetry by TML system.

This study proposes a system for classifying facial asymmetry with accompanying mandibular prognathism to facilitate choice of surgical method. We examined hard and soft tissue measurements obtained from posterior-anterior cephalometric radiographs and clinical facial photographs of 153 patients (86 male, 67 female), classifying them according to menton deviation with transverse asymmetry (T), maxillary cant (M), and lip cant (L). The T-group is subclassified according to direction of transverse asymmetry (H). Statistical analysis of menton deviation, cant and transverse asymmetry was performed for each group. The various relationships observed among the groups indicate that most cases (85%) were not effectively correctable using conventional surgical methods. As such, the authors believe that analysing facial asymmetry in terms of the classification system presented in this study and employing surgical methods appropriate to each case will help achieve more harmonious aesthetic outcomes.

Assessment of 2D:4D in subjects with anteroposterior mandibular dysplasia.

OBJECTIVES: To compare 2D:4D ratio which is determined by testosterone levels with patients having orthognathic, retrognathic and prognathic mandibles. MATERIALS AND METHODS: The study was performed at Chennai, on 320 subjects of which, 60 subjects (32 males and 28 females) had retrognathic mandible; 55 subjects (25 males and 30 females) had prognathic mandible and 205 subjects (98 males and 107 females) had normal mandible. All the subjects had a normal maxilla and were in the age group of 18 to 25 years. 2D:4D ratio was determined using the photocopies of the ventral surface of right hand made with vernier calipers of 0.01 mm accuracy. Statistical analysis was undertaken using Student's t- test, ANOVA test and TukeyHSD test. RESULTS: (i) Low 2D:4D is seen in subjects with mandibular prognathism, (ii) Among females, low 2D:4D is seen only in prognathic mandible. CONCLUSION: These findings highlight the fact that testosterone plays an important role in mandibular growth. Thus 2D:4D, a least invasive and reproducible procedure can be used as an early marker for mandibular progathism, and as a diagnostic tool in correlating the mandibular growth with causal relations between hormones and craniofacial development.

Postsurgical stability after mandibular setback surgery with minimal orthodontic preparation following upper premolar extraction.

PURPOSE: To compare patterns of surgical change and postsurgical relapse between patients with mandibular setback surgery with minimal orthodontic preparation (MS-MO) and those with sufficient orthodontic preparation (MS-SO) after upper premolar extraction (UPE). MATERIALS AND METHODS: Twenty-six patients were allocated to 2 groups based on the duration of presurgical orthodontic preparation: MS-MO/UPE (n = 15; 5.53 ± 3.14 months) and MS-SO/UPE (n = 11; 13.00 ± 5.33 months). Lateral cephalograms were taken during the initial examination (T0), at splint removal (4 weeks after surgery; T1), and immediately after debonding (T2). To evaluate the surgical changes (T1 vs. T0) and relapse (T2 vs. T1), linear, angular, and dental measurements were used and analyzed using paired t test and independent t test. RESULTS: Although there was no significant difference in skeletodental patterns at T0 between the 2 groups, the MS-MO/UPE group showed a significantly larger amount of mandibular setback than the MS-SO/UPE group from T0 to T1. The 2 groups exhibited significant anterior and superior movement of the mandible from T1 to T2. However, the MS-MO/UPE group manifested greater counterclockwise rotation and forward movement of the mandible than the MS-SO/UPE group. Owing to such relapse of the mandible, the MS-MO/UPE group exhibited limited retraction of the upper incisors, whereas the MS-SO/UPE group showed slight labioversion of the upper incisors. CONCLUSION: Compared with the MS-SO/UPE group, the MS-MO/UPE group showed a larger amount of surgical setback and greater postsurgical counterclockwise rotation and forward movement of the mandible.

Extreme mandibular dentobasal discrepancy in orthognathic surgery: a proposal for a definitive solution.

Some cases in orthognathic surgery present with large discrepancies between the skeletal pattern and the occlusion. If there is little or no sagittal dental discrepancy, but the mandibular basal bone is prognathic, surgical correction can be critical. We describe a two-step procedure to treat these patients. The first step is to adapt the lower alveolar bone to the position of the chin. Distraction osteogenesis in the anterior dentoalveolar mandibular region carries the lower incisors to the same level as the chin. A one-tooth space is opened in the distraction area to obtain a full negative over-jet. Bimaxillary osteotomy can be used to correct class III dentoskeletal malocclusion. Five patients aged 20-40 years have been operated on during the last 2 years. The first step creates harmony between the chin and lower lip, together with a negative over-jet and a true prognathic profile. The class III malocclusion is corrected with a bimaxillary osteotomy. Our two-step plan achieves good occlusion and profile in patients with severe discrepancies between their occlusion and the position of the chin. Dental implants can then be inserted into the gaps left by distraction, which results in a third bicuspid on each side of the mandible.

Effect of bone quality and position of the inferior alveolar nerve canal in continuous, long-term, neurosensory disturbance after sagittal split ramus osteotomy.

OBJECTIVES: To examine the relationship between the anatomical position and the bone quality of the inferior alveolar nerve (IFAN) canal and long-term neurosensory disturbance (NSD) of the IFAN after a sagittal split ramus osteotomy (SSRO). MATERIAL AND METHODS: CT images were taken of patients with mandibular prognathism. The location of the IFAN and the bone density around the IFAN were measured on CT images. Whether NSD at 6 months and 1 year after SSRO was related to the position and bone quality of the IFAN canal was analyzed. RESULTS: Significant correlations were found between the anatomical position and the bone quality of the IFAN canal and the period to the resolution of NSD of the IFAN from 3 months to 1 year after SSRO. If the HU values around the IFAN were greater than 300 HU and/or the distance from the buccal aspect of the IFAN canal to the outer buccal cortical margin was less than 6 mm, NSD of the IFAN at 1 year after SSRO was significantly increased. CONCLUSION: It is important to pay particular attention to the anatomical position of the IFAN and the bone quality around the IFAN to predict long-term NSD of the IFAN after SSRO.

Three-dimensional analyses of facial soft tissue configuration of Japanese females with jaw deformity--a trial of polygonal view of facial soft tissue deformity in orthognathic patients.

In this study, we evaluated the three-dimensional (3D) soft tissue configuration of Japanese females with/without jaw deformity in order to establish the polygonal view of facial soft tissue deformity three-dimensionally. A polygonal chart was applied to assess the outcomes of orthognathic surgery for patients with mandibular hyperplasia with/without deviation. The study included 20 Japanese females with mandibular hyperplasia with/without deviation. All patients received mandibular setback surgery, and 3D measurements were carried out pre-operation, and at 1, 3 and 6 months postoperatively using a non-contact laser scanning system. Eighteen soft tissue landmarks were set on each 3D image and used to calculate a set of selected parameters. As controls, 20 Japanese females with class I occlusion were included. A polygonal chart was constructed based on the mean and S.D. of the control group. Patients with mandibular protrusion characteristically demonstrated significant variances in the items around the lower face. In asymmetric patients, deviation in the mental area disappeared postoperatively, but a small deviation remained when compared to the controls. The method used in this study seems to be a useful index for diagnosis and as a treatment plan for patients with mandibular hyperplasia with/without deviation.

Maxillofacial characteristics affecting chin deviation between mandibular retrusion and prognathism patients.

OBJECTIVE: To examine and compare the maxillofacial characteristics affecting chin deviation three-dimensionally in facial asymmetry patients with mandibular retrusion and mandibular prognathism. MATERIALS AND METHODS: Maxillofacial computed tomography (CT) scan data were obtained from 48 orthognathic surgery patients (24 cases of mandibular retrusion and 24 cases of mandibular prognathism) with facial asymmetry. Although chin deviation was assessed on the basis of the ANS-to-menton line on frontal cephalograms, its contributing factors were evaluated on three-dimensional CT images. Maxillary height, ramus length, frontal ramal inclination, lateral ramal inclination, mandibular body length, and body height were defined on each side, and right-left differences were calculated and analyzed. RESULTS: In an assessment of chin deviation, subjects in this study showed predominantly left side deviation regardless of the group, and the degree of menton deviation did not reveal significant differences between groups. In a comparison of right-left differences in contributing factors, all values were noted to be greater in the retrusion group, except for body height, which showed no difference between chin-deviated and contralateral sides. In particular, ramus length presented a statistically significant difference between the two groups. CONCLUSION: Based on the same degree of chin deviation in mandibular prognathism and retrusion in this study, results of right-left differences in contributing factors indicate that chin deviations are expressed easily in mandibular prognathism, whereas they occur only with significant right-left differences in relevant maxillofacial structures in individuals with mandibular retrusion.

Acromegaly: a cross-sectional analysis of the oral and maxillofacial pathologies.

CONTEXT: It is well established that clinical features of acromegaly concern the teeth and the jaw, but less is known about the degree of oral and maxillofacial pathologies. PATIENTS: 28 acromegalics (13 females, 15 males) with a mean age 49±11 (mean±SD) years (range 31-70) were included in the study. 32% had active disease, 68% were well-controlled under the somatostatin analogue octreotide, the dopamine agonist cabergoline, and the GH receptor antagonist pegvisomant, or were cured after pituitary surgery and/or radiation. METHODS: All subjects undergone intensive and complex examinations of a plaster model and facial arch with articulator, an intra-oral bracket-pen registration, analysis of a digital picture, panoramic and lateral radiographs with cephalometry in comparison with a reference group (n=201). RESULTS: 42% had a diastema mediale (0.9±1.1 mm). Overbite and overjet (vertical overbite) correlated with the disease duration (r²=0.2237; p=0.011 respectively r²=0.3364; p=0.015). 96% had an asymmetric movement of the mandible. 57% had a prognathism. The protrusion of the mandible correlated significantly with the disease duration (r²=0.1784; p=0.028). The degree of the mandibular prognathism (SNB-angle) was higher in the acromegalic group (84°±7° vs. 81°±3°, p<0.05). The ANB-angle indicates the relation between maxilla and mandible and was negative in the acromegalic group and positive in the controls (-0.3°±5.0° vs. 1.6°±2.1°, p=<0.05) and correlated negative with the disease duration (r²=0.2553; p=0.0061). The mandibular angle was significantly greater in the acromegalic group (126°±9° acromegalic group vs. 121°±7°control group, p=0.003). The length of the mandible correlated with the disease duration (r²=0.2801; p=0.0038). 86% had an asymmetric face. The high of the midface was in the acromegalic group higher (6.1±0.7 vs. 5.5±0.4 cm, p=0.0009) as well as the lower bony high of the face (9.5±1.0 acromegalics vs. 6.9±0.5 cm controls, p=0.0009). The high of the lower bony face correlated with as well with the disease duration (r²=0.3224; p=0.0016). CONCLUSIONS: Patients with acromegaly suffer not only from cardiovascular, metabolic and neoplastic complications, but also from dental and jaw disorders. The high incidence of these manifestations and its relation to the disease duration requires a carefully work-up of oral and maxillofacial examinations in close collaboration with endocrinologists, dentists and dental surgeons.

Novel method of 3-dimensional soft-tissue analysis for Class III patients.

INTRODUCTION: The aim of this study was to evaluate 3-dimensional facial shells by incorporating a population-specific average template with a group of Class III subjects preparing to have orthognathic surgery. METHODS: The Class III group included 14 male (MCIII) and 15 female (FCIII) subjects. We used 43 male and 44 female Class I subjects to construct average male (AvM) and female (AvF) faces. Coordinates of 3 points on the facial templates of groups MCIII and FCIII and the templates AvM and AvF were compared. MCIII-AvM and FCIII-AvF superimpositions were evaluated for differences. RESULTS: Vertical distances (sella to soft-tissue pogonion) were statistically significantly higher for the AvM (9.1%) and MCIII (10.1%) than for the AvF and FCIII, respectively (P < 0.05). The distances of soft-tissue pogonion in the horizontal x-axis were positive in 80% of the FCIII group and 85.7% of the MCIII group. The Class III subjects differed from the average face in the lower two thirds, but, in 50% (MCIII) and 60% (FCIII), they differed also in the upper facial third. CONCLUSIONS: (1) The average and Class III Slovenian male morphologic face heights are statistically significantly higher than those of the female subjects. (2) The Slovenian Class III male and female subjects tend toward a left-sided chin deviation. (3) Differences between Class III patients and a normative data set were determined.

Evaluation of mandibular ramus morphology using computed tomography in patients with mandibular prognathism and retrognathia: relevance to the sagittal split ramus osteotomy.

PURPOSE: The purpose of this study was to evaluate and compare the thickness of the mandibular ramus in patients with mandibular prognathism and retrognathia, as well as to assess the distribution of cancellous bone between the external and internal cortical plates above and posterior to the lingula. PATIENTS AND METHODS: The mandibular ramus of 40 patients, of whom 20 had prognathism and 20 had retrognathia, were evaluated by use of high-resolution computed tomography scanning. RESULTS: The mean thickness of the ramus in the prognathism group was 8.17 mm, which differed significantly from the mean value of 8.88 mm in those with retrognathia (P = .014). The mean vertical distance of the point of fusion between the cortical plates above the lingula was 8.95 mm for patients with prognathism and 9.41 mm for those with retrognathia, which was not a significant difference (P = .364). The mean horizontal distance of the point of fusion between the cortical plates posterior to the lingula was 8.32 mm for patients with prognathism and 9.74 mm for those with retrognathia, which was also not a significant difference (P = .066). CONCLUSIONS: The mandibular ramus is thinner in patients with prognathism than in those with retrognathia. The distance of the point of fusion between the cortical plates above and posterior to the lingula is not influenced by the 2 types of mandibular deformity evaluated in this study. Computed tomography has proven to be a valuable tool to evaluate the morphology of the mandibular ramus.