Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Inferior alveolar nerve sensory disturbance after impacted mandibular third molar evaluation using cone beam computed tomography and panoramic radiography: a pilot study.

PURPOSE: To measure sensory disturbances of the inferior alveolar nerve (IAN) after removal of impacted mandibular third molars using cone beam computed tomography (CBCT) and dental panoramic radiography (PAN) for preoperative assessment in a randomized controlled trial and to measure the efficacy of the observers' prediction of IAN exposure at surgery based on CBCT compared with PAN. MATERIALS AND METHODS: The sample consisted of 86 impacted third molars (from 79 consecutive patients) in close relation to the IAN as determined by PAN and judged as showing a "moderate" risk of IAN damage. Cases presenting with no close relation between the IAN and roots and extremely risky cases with an obvious interrelation were excluded. Potential neurosensory disturbances of the lip and chin were assessed before surgery and during the postoperative recall by measuring the function of the IAN with the light-touch sensation method. RESULTS: Postoperative sensory disturbances occurred in 1 patient in the CBCT group and 1 patient in the PAN group. The light-touch sensation test showed no significant differences at the lip (P = .10) and chin (P = .17) levels for CBCT- versus PAN-based surgery. Significant differences in making a correct diagnosis of neurovascular bundle exposure at the extraction of impacted teeth were found between the 2 modalities (P = .029). CONCLUSIONS: Within the limits of the present pilot study, CBCT was not superior to PAN in predicting postoperative sensory disturbances but was superior in predicting IAN exposure during third molar removal in cases judged as having "moderate" risk.

Contribution of three-dimensional images in the planning of cementoblastoma resection.

Cementoblastomas are rare benign tumours that represent less than 1% of all odontogenic tumours. Complete resection is mandatory to avoid recurrence. This case report describes the contribution of three-dimensional imaging and three-dimensional printing in the pre-operative surgical planning of a large cementoblastoma that not only caused substantial compression on the inferior alveolar and mental nerves, but also caused thinning and partial erosion of the lingual and vestibular cortical bone, thus increasing the risk of pre-operative mandibular fracture.

Orthodontic and orthognathic management of a patient with Apert syndrome: a case report.

This case report describes the combined orthodontic and orthognathic management of a 14-year-old girl affected with Apert syndrome. She presented with a severe Class III skeletal relationship, midfacial hypoplasia and an large anterior open bite. Intraorally, she had severe crowding, a narrow maxilla and lateral posterior crossbites. The patient was treated with a combination of removable and fixed appliances, a transpalatal skeletal distractor and Le Fort I surgery. The extraoral characteristics improved and a good occlusal relationship between maxillary and mandibular teeth was achieved.

Fibula Free Flap in Head and Neck Reconstruction: Identifying Risk Factors for Flap Failure and Analysis of Postoperative Complications in a Low Volume Setting.

The fibula free flap (FFF) has been a workhorse in maxillofacial reconstruction. High success rates of this technique are reported. However, identifying risk factors for flap failure and analyzing complications can open the way to better patient care. A retrospective analysis was conducted of all FFFs performed over a 20-year period at a low-volume single tertiary center to identify risk factors and postoperative complications. A total of 129 FFFs were included (122 mandible, 7 maxilla). Complete flap failure occurred in 12.4% and partial flap failure in 7.8% of patients. A significant relation was found between younger age and flap failure, and most failures were associated with venous thrombosis. In-hospital surgical complications occurred in 60.5%, in-hospital medical complications in 49.6%, and out-of-hospital complications in 77.5% of patients. The in-hospital reintervention rate was 27.1%, and including salvaged flaps, flap survival rate was 87.6%. Osteomyocutaneous FFF failure (complete 12.4%; partial 7.8%) is an important clinical reality in a low-volume head and neck reconstruction center resulting in an in-hospital reintervention rate of 27.1%. Postoperative complications are frequent, both surgical and out-hospital complications. These results provide a better understanding of the limitations of the FFF in a low-volume center and can be used to optimize care in this kind of setting.

Accuracy of computer-assisted mandibular reconstructions with free fibula flap: Results of a single-center series.

OBJECTIVES: We evaluated the accuracy of computer-assisted mandibular reconstructions. PATIENTS AND METHODS: We retrospectively reviewed data for 26 patients who had mandibular reconstruction with a microvascular free fibula flap, January 2015 to June 2018. Postoperative mandible models were obtained from computed tomography scans. After registering the models to the corresponding preoperative plan, we performed comparative measurements. Patients were grouped by condylar involvement and subdivided based on number of fibular segments used for reconstruction. For each segment, we measured length and osteotomy angles. For the final postoperative outcome, we compared intercoronoid, intergonial, and anteroposterior distances and intersegmental plane shift. RESULTS: Means (SD) for deviation of each osteotomy angle and fibular segment length were 1.98° (2.98) and 1.78 mm (2.69), respectively, remaining constant across subgroups. Other mean values were as follows: intercoronoid distance deviation, 3.86 mm (range, 0.20-11.21 mm); intergonial distance deviation, 3.14 mm (range, 0.05-8.28 mm); anteroposterior distance deviation, 2.92 mm (range, 0.03-8.49 mm); and intersegmental plane shift, 11.00° (range, 2.76-24.15°). Where the condyle was preserved, the intercoronoid and intergonial deviation means differed significantly (respectively 5.02 mm and 4.88 mm, both P < 0.05) for one-segmented and three-segmented fibular reconstructions. Furthermore, reconstructions involving the condylar region compared with condyle preservation showed significantly different intersegmental plane shifts (7.18°; P < 0.05). CONCLUSION: Computer-assisted surgery provides cutting guides for obtaining accurate fibular segments, but current fixation methods lead to inaccuracies and reproducibility errors. In multisegmental transfer with condylar involvement, computer-assisted fixation is recommended to ensure accuracy of the preoperative plan.

Incidence of osteonecrosis of the jaw in patients with bone metastases treated sequentially with bisphosphonates and denosumab.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a serious adverse event of bone resorption inhibitors (BRIs), such as bisphosphonates and denosumab. Bisphosphonates and denosumab inhibit osteoclast function through different pharmacological effects and bisphosphonates are retained in bone for several months to years. Sequential treatment with bisphosphonates and denosumab might lead to an overlapping treatment effect, due to the addition of the effect of denosumab on the residual bisphosphonate effect. Therefore, the aim of our study was to investigate if switching from denosumab to bisphosphonates is associated with a higher incidence of ONJ. METHODS: We retrospectively reviewed records of patients with solid tumors and bone metastases treated with denosumab after prior treatment with bisphosphonates at the University Hospitals Leuven (sequential group). Patients treated with denosumab or bisphosphonates alone were used as control groups. RESULTS: We identified 110 patients sequentially treated with bisphosphonates and denosumab with a median total BRI exposure of 36 months (sequential group). Median bisphosphonates exposure was 16 months and median denosumab exposure was 13 months. About 299 patients were included in the bisphosphonates control group with a median bisphosphonate exposure 19 months. About 6.7% (20/299) of patients developed ONJ. About 240 patients were included in the denosumab control group with a median denosumab exposure 17.5 months. About 10.0% of patients (24/240) developed ONJ. In the sequential group, 15.5% of patients (17/110) developed ONJ. The incidence of ONJ was 1.8% (2/110), 6.3% (6/99), 4.9% (4/82), 5.6% (3/54), and 3.4% (1/29), respectively in the first, second, third, fourth, and fifth year of BRI exposure, an ONJ-incidence similar to ONJ-incidence in the denosumab control group. In a time-to-ONJ-analysis, the curves of the sequential group and the denosumab control group were overlapping. In the sequential group, most of the ONJs occurred in the first year of denosumab exposure and in a matched control group analysis, with correction for median BRI-exposure, ONJ cases tend to occur earlier in the sequential group compared to ONJ cases in the bisphosphonates group. CONCLUSION: Cancer patients with bone metastases treated with BRIs seem to have a slightly higher risk of ONJ early after switching from bisphosphonates to denosumab compared to patients remaining on bisphosphonates. Nevertheless, based on the global ONJ-incidence, the switch from bisphosphonates to denosumab can be considered as safe as an equivalent exposure to denosumab from the start on.

Retrospective Analysis of Dental Implants Placed Between 2012 and 2014: Indications, Risk Factors, and Early Survival.

PURPOSE: The aim of this study was to review the indications for implant placement, early outcomes, and associated risk factors. MATERIALS AND METHODS: A retrospective cohort study design was used. The study was composed of a group of 509 consecutive patients, which represented the total number of patients treated from 2012 to 2014 in the Department of Oral and Maxillofacial Surgery, University Hospitals Leuven, Belgium. The authors analyzed the indications for implant placement and the potential risk factors for early implant failure. RESULTS: A total of 509 patients received 1,139 dental implants. The group consisted of 240 men and 269 women, with a median age of 58 years. The most frequent indication for implant placement was restoration of a partially edentulous arch (80.1%, n = 408). For 152 implants (13.3%), additional bone-augmentation or sinus elevation procedures were required. Early failures were recorded for 52 (4.6%) implants in 33 patients (6.5%). Smoking, male gender, total edentulism, implant diameter, and bone augmentation surgery were found to be associated with early implant failure. CONCLUSION: Patients referred for implant placement were more likely to be partially edentulous and older than 50 years. Singletooth replacement in the posterior mandible was the most frequent indication (24.4%) for treatment. This study found an early success rate of 95.4% and identified risk factors for early failures.

Wound Healing Problems in the Mouth.

Wound healing is a primary survival mechanism that is largely taken for granted. The literature includes relatively little information about disturbed wound healing, and there is no acceptable classification describing wound healing process in the oral region. Wound healing comprises a sequence of complex biological processes. All tissues follow an essentially identical pattern to complete the healing process with minimal scar formation. The oral cavity is a remarkable environment in which wound healing occurs in warm oral fluid containing millions of microorganisms. The present review provides a basic overview of the wound healing process and with a discussion of the local and general factors that play roles in achieving efficient would healing. Results of oral cavity wound healing can vary from a clinically healed wound without scar formation and with histologically normal connective tissue under epithelial cells to extreme forms of trismus caused by fibrosis. Many local and general factors affect oral wound healing, and an improved understanding of these factors will help to address issues that lead to poor oral wound healing.

Primary intraosseous squamous cell carcinoma of the mandible arising from an infected odontogenic cyst: A case report and review of the literature.

Primary intraosseous squamous cell carcinoma (PIOSCC) derived from a odontogenic cyst is a rare form of odontogenic carcinoma. The incidence of carcinomas arising from odontogenic cysts is particularly uncommon and is reported to occur in 1-2 individuals for every 1,000 cases. The present case describes a 25-year-old man who was initially diagnosed with a chronically infected odontogenic cyst of the mandible. Biopsy and subsequent histology revealed the presence of squamous cell carcinoma. Therefore, neck dissection and hemimandibulectomy were performed. Ultimately, the situation in the mouth healed, though with a severe amount of scarring. Although the development of PIOSCC from an odontogenic cyst is rare, it should be included in the differential diagnosis for jaw bone radiolucency.

Combined surgical/orthodontic treatment and autotransplantation of a premolar in a patient with unilateral cleft lip and palate.

OBJECTIVE: The treatment of a patient with a complete unilateral left cleft lip and palate, agenesis of the left upper second premolar, and a severely malformed left upper lateral incisor is reported. Treatment included placement of an autologous bone graft from the left iliac crest into the alveolar cleft at 8 years of age and transplantation of a lower premolar into the reconstructed alveolar process at 10 years of age. During the succeeding orthodontic treatment, the dental arches were aligned and corrected toward a Class I molar occlusion. One year after the end of treatment, the status of the transplanted premolar was good.