Identification of a Novel Mutation in the Runt-Related Transcription Factor 2 Gene in a Chinese Family With Cleidocranial Dysplasia.

ABSTRACT: Cleidocranial dysplasia (CCD) is an uncommon autosomal dominant disease, characterized by hypoplasia of clavicles, delayed fontanelle closure, dental anomalies, and short stature. It has been reported in the literature that the pathogenic variants of Runt-related transcription factor 2 (RUNX2) gene are correlated with CCD patients.Here, we report a consanguineous Chinese family with 2 patients suffering from CCD, presenting similar skeleton and dentition malformation. Upon whole-exome sequencing, 52863 variants were detected in the propositus. Based on the genotype phenotype correlation, a frameshift deletion c.1554delG p.(Trp518Cysfs∗61), located in exon 8 of RUNX2, remained after filtration. For Sanger sequencing, all exons of the RUNX2 gene in members of this Chinese family were amplified by polymerase chain reaction. Mutation mentioned above was confirmed in the propositus and his mother, which has not been reported previously and cannot be found in the publicly available databases. The present study expands the pathogenic variant spectrum of RUNX2 gene and contributes to molecular diagnosis.

Enhanced osteogenesis of quasi-three-dimensional hierarchical topography.

Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

[Clinical application and accuracy analysis of occlusion-guided functional mandibular reconstruction].

OBJECTIVE: To investigate the influence of the design and application of novel surgical template on the accuracy of reconstructed mandibula and implant position in occlusion-guided functional mandibular reconstruction, so as to provide guidance for clinical treatment. METHODS: Between January 2017 and May 2019, 11 patients with segmental mandible defects were treated, including 8 males and 3 females with an average age of 31.8 years (range, 19-45 years). There were 6 cases of ameloblastoma, 3 cases of keratocystic tumor, and 2 cases of ossifying fibroma. According to Urken classification of mandible defects, there were 1 case of CRB, 4 cases of RB, 2 cases of RBS, and 4 cases of SB. According to the occlusion relationship, a novel surgical template with the reconstruction titanium plate screws and implants drill-guided information was designed and manufactured. With the help of the novel surgical template, the "one and a half" fibula reconstruction mode was used for jaw functional reconstruction, and the implant supported denture was finally completed. The postoperative CT at 1 week were collected to analyze the morphology of the preoperative virtual design jaw and postoperative jaw. The coincidence of fibular reconstructed mandible (fibular upper barrel, fibular reconstructed ramus and condyle, and whole mandible) and implant in mandible were calculated. When the coincidence was less than 80%, it was considered that the deviation was obvious. Oral panoramic X-ray film and cone beam CT were examined at 6 months after operation to evaluate the osseointegration before implant repair. RESULTS: None of the 11 flaps had postoperative vascular crisis. One flap occurred necrosis at 1 month after reconstruction combined with 3 implants failed, and had been removed at 6 months after reconstructed surgery; the others had no flap necrosis. One week postoperatively, the coincidence of the fibular upper barrel was 87.55%±3.08%, the whole mandible was 82.68%±5.94%, and the implant in mandible was 88.00%, with significant differences ( t=8.131, P=0.000; t=2.118, P=0.046; Z=4.070, P=0.000) when compared to 80%, respectively. The fibular reconstructed ramus and condyle was 77.82%±3.54%, with no significant difference ( t=-2.042, P=0.068) when compared to 80%. Six months postoperatively, oral panoramic X-ray film and cone beam CT showed that all 22 implants achieved osseointegration and the palatal mucosa transplantation was performed, then finally completed the denture rehabilitation at 6-9 months after operation. All patients were satisfied with their postoperative appearance. CONCLUSION: The novel surgical template can guarantee the accuracy of functional mandible reconstruction guided by occlusal guidance, and ultimately achieve the beautiful contour of jaw and occlusal function reconstruction, and improve the patient's life quality.

Utilization of a pre-bent plate-positioning surgical guide system in precise mandibular reconstruction with a free fibula flap.

OBJECTIVES: We evaluated the effects of three-dimensional virtual planning and the use of a plate-embedded surgical guide in mandibular reconstruction with microvascular fibula flaps. MATERIALS AND METHODS: We retrospectively reviewed 35 patients who underwent primary mandibular reconstruction with a free fibula flap. They were divided into three groups according to the therapy they received. In group A, 12 patients underwent reconstruction using the modified surgical guide system, including virtual surgeries, pre-bent titanium plates, screw-predesignated cutting guides for mandibular and fibular osteotomies, and plate-embedded shaping guides. In group B, 14 patients underwent reconstruction using the common surgical guide system, including virtual surgeries, cutting guides and pre-bent plates. In group C, 9 patients underwent reconstruction based on the surgeon's experience. All cases were reviewed for the total operative time, ischemia time of the fibula flaps, accuracy of surgery, and postoperative complications. RESULTS: All of the fibula flaps survived. In group A, the ischemia time was shorter than that of groups B and C (P < .05). The average gonion and condyle shift was lower in group A than in groups B and C (P < .01). CONCLUSIONS: Application of the screw-predesignated and plate-embedded surgical guide system can reduce the ischemia time and operation time in mandibular reconstruction with a fibula flap, and can increase reconstruction accuracy. This method is a precise and highly reliable technique for improving the clinical outcome of mandibular reconstruction.

Pedicled partial thickness clavicular graft for oromandibular reconstruction.

OBJECTIVE: To report our experience on pedicled partial-thickness clavicular graft (PPCG) for oromandibular reconstruction. STUDY DESIGN: PPCG was used for oromandibular reconstruction after tumor resection in 23 patients with early-stage gingival carcinoma but were eager for postoperative dental implant therapy for restoration of good occlusal function. PPCG was harvested during neck dissection. The sternocleidomastoid (SCM) myocutaneous flap was also harvested in 18 cases. Dental implants were placed in the clavicular graft of 19 cases, and the other 4 declined because of financial concerns. Postoperative viability of the flaps and the dental implants were assessed. RESULTS: All the clavicular grafts survived without necrosis and implant-supported dentures of 19 patients provided satisfactory occlusion and masticatory function. Complications, although low in occurrence, included partial skin pedicle loss, nonunion between the clavicular graft and the remaining inferior border of the mandible, and clavicular bone fracture. CONCLUSIONS: PPCG is a simple but reliable procedure for reconstruction of severe alveolar defects. Correct preoperative evaluation and precise surgical technique contribute to higher success rates and lower complication rates. It is a viable reconstructive option for early-stage gingival carcinoma requiring neck dissection without postoperative radiation therapy.

[MEDIAL SURAL ARTERY PERFORATOR FREE FLAP FOR REPAIR OF DEFECT AFTER TONGUE CANCER ABLATION].

OBJECTIVE: To investigate the effectiveness of medial sural artery perforator free flap (MSAP) for repairing defect after tongue cancer ablation. METHODS: Between March 2013 and April 2014, the defects after tongue carcinoma resection were repaired with MSAP in 12 patients, including 8 cases of high or medium differentiated squamous cell carcinoma (SCC) and 4 cases of moderately-poor differentiated SCC. There were 7 males and 5 females with a median age of 55 years (range, 45-68 years). The disease duration ranged from 2.0 to 8.5 months (mean, 4.3 months). The tumor located at the tongue edge in 8 cases and at the tongue abdomen in 4 cases (mouth floor infiltration in 1 case). According to TNM stage, 7 cases were rated as T2N0M0, 2 cases as T2N1M0, 2 cases as T3N1M0, and 1 case as T4N1M0. The size of tumor ranged from 3.0 cm x 2.0 cm to 4.5 cm x 3.0 cm. The size of MSAP varied from 4.0 cm x 3.5 cm to 6.5 cm x 6.0 cm. RESULTS: The time of total operation ranged from 5.5 to 8.3 hours (mean, 6.8 hours), and flap harvesting time ranged from 54 to 85 minutes (mean, 65.6 minutes). The other flaps survived except 1 case of vein crisis. All the patients were followed up 6-18 months (mean, 13.7 months). With time passing, the pronunciation got better, and the skin showed mucosa-like change; the patients were capable of normal language exchange at 6 months after operation. No obvious scar on the leg or limitation of limb motion was observed. CONCLUSION: The MSAP is reliable for repair of defect after tongue cancer ablation, with the advantages of satisfactory recovery of tongue appearance, language function, and less donor site morbidity.

[INITIAL APPLICATION OF COMPUTER ASSISTED NAVIGATION SYSTEM IN RECONSTRUCTION OF MANDIBULAR DEFECTS].

OBJECTIVE: To evaluate the value of computer assisted navigation system (CANS) in the reconstruction of mandibular defects. METHODS: Between April 2012 and September 2014, 8 patients with mandibular defects were included in this study. There were 5 males and 3 females with an age range of 22-50 years (mean, 34.5 years), including 4 cases of ameloblastoma, 3 cases of odontogenic keratocyst, and 1 case of condylar osteoma. According to the CRABS (condyle, ramus, angle, body, symphysis) classification criteria based on the location of mandibular defect, there were 1 case of right CRAB type, 1 case of left RABS type, 1 case of left CR type, 1 case of right RAB type, 1 case of left C type, 1 case of right RABS+left S type, and 2 cases of right AB type. With the biteplate fixing mandible, maxillofacial CT and the donor site CT scan were done. Computer assisted design was made by using Surgicase CMF5.0 software and BrainLab Iplan software, included delineating the osteotomy lines for resection, ascertaining the normal anatomic structures for defect reconstruction, and determining the reconstructive morphology. With guide plates and the guidance of BrainLab navigation system, an en bloc tumor resection and simultaneous defect reconstruction were performed under the precise localization of mandibular angle and condyle. Preoperative and postoperative CT images were superimposed in Geomagic studio12.0 software system, and both were compared by three-dimensional (3D) objects and 2D slices. The complications and signs of recurrence were observed. RESULTS: Under the guidance of navigation, preoperative facial symmetry design, surgery simulation, and simultaneous navigation operation were performed successfully. The postoperative CT and postoperative 3D error analysis showed osteotomy lines and reconstruction contour had good matching with the preoperative planning. The error of important corresponding points (mandibular angle and external pole of condyle) in the reconstruction of mandibular defects were (1.83 ± 0.19) mm and (1.61 ± 0.24) mm. The patients were followed up 2-6 months (mean, 3.5 months). No complication was observed in the other patients except the patients undergoing rib transplantation who had mild limitation of mouth opening. Good facial symmetry was obtained, and no tumor recurrence was found. CONCLUSION: CANS can effectively increase the surgical precision in the reconstruction of mandibular defects and reduce complications, and recover facial symmetry. It is regarded as a valuable technique in this potentially complicated procedure.

[Application of three-dimensional printing technique in repair and reconstruction of maxillofacial bone defect].

OBJECTIVE: To explore the application of three-dimensional (3-D) printing technique in repair and reconstruction of maxillofacial bone defect. METHODS: The related literature on the recent advance in the application of 3-D printing technique for repair and reconstructing maxillofacial bone defect was reviewed and summarized in the following aspects: 3-D models for teaching, preoperative planning, and practicing; surgical templates for accurate positioning during operation; individual implantable prosthetics for repair and reconstructing the maxillofacial bone defect. RESULTS: 3-D printing technique is profoundly affecting the treatment level in repair and reconstruction of maxillofacial bone defect. CONCLUSION: 3-D printing technique will promote the development of the repair and reconstructing maxillofacial bone defect toward more accurate, personalized, and safer surgery.

Use of the versatile sternocleidomastoid flap in oral and maxillofacial surgery: our experience.

Our aim was to evaluate the reliability of sternocleidomastoid (SCM) flaps in the reconstruction of defects after oral and maxillofacial resections, and summarise the ways in which morbidity can be reduced. We retrospectively enrolled 65 patients who had malignant tumours resected, and assessed the postoperative viability of the SCM flap. All complications were recorded during a follow up period of 1-64 months. We also investigated the relation between recurrence in regional lymph nodes and their preoperative histological state. The conventional SCM flap, the split SCM flap with only the sternal head, and the SCM flap with a half-thickness clavicular graft, were used to repair different defects. No flaps necrosed completely, and in only 5 cases was there partial loss of the skin paddle. The skin paddle avulsed in 2 cases 2 patients developed wound infections. Only 9 patients developed complications (14%, 9/65). Use of the split SCM flap overcomes the problem of bulk. The combination of the SCM flap and clavicular bone enables early dental implantation. The SCM flap is convenient, reliable, and technically easy for the reconstruction of intraoral or mandibular tissue loss. Preservation of the branch of the superior thyroid artery and precise surgical technique contribute to a higher success rate.

[Using sternocleidomastoid-clavicle myocutaneous flap to reconstruct compound operative defect of oral carcinoma].

OBJECTIVE: To study the sternocleidomastoid-clavicle myocutaneous flap (SCMCP) for repairing the compound operative defect after oral carcinoma resection, to observe its clinical effect, prognosis and advantages of SCMCP, and to develop a new operative method that implantation of dental implant can be performed simultaneously. METHODS: Sixteen patients underwent reconstruction with SCMCP after oral carcinoma resection and neck dissection during 2007 to 2009. Four of them (25.00%) underwent simultaneously implantation of dental implants in the clavicular flaps. RESULTS: None of these patients died postoperatively during the follow-up until now. One patient (6.25%) with buccal cancer encountered local recurrence resulting in reoperation, and the flap grows well up to now. A part of the skin paddle underwent necrosis in two patients (12.50%), local fluidity was found in 2 patients (12.50%), fracture of clavicle occurred during the operation in one patient (6.25%). All the patients had good pronunciation and oral diet with no difficulty. CONCLUSION: SCMCP is easy to survive, simple to perform, the clavicular figure and function won't be destroyed significantly. SCMCP is a good operative method to repair the compound operative defect after oral carcinoma resection.