De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction.

Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H2O2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue.

Following in the footsteps of Hippocrates-interrelation between the incidence of odontogenic abscess and meteorological parameters.

OBJECTIVES: Although many physicians in daily practice assume a connection between odontogenic infections and meteorological parameters, this has not yet been scientifically proven. Therefore, the aim of the present study was to evaluate the incidence of odontogenic abscess (OA) in relation to outdoor temperature and atmospheric pressure. PATIENTS AND METHODS: An analysis of patients with an odontogenic abscess who presented at the emergency department within a period of 24 months was performed. Only patients who had not received surgical or antibiotic treatment prior to presentation and who lived in Berlin/Brandenburg were included. The OA incidence was correlated with the mean/maximum outdoor temperature and atmospheric pressure starting from 14 days before presentation. The statistical analysis was carried out using Poisson regression models with OA incidence as dependent and meteorological parameters as independent variables. RESULTS: A total of 535 patients (mean age 39.4 years; range 1 to 95 years) with 538 cases were included. Of these, 227 were hospitalized. The most frequent diagnosis was a canine fossa abscess. A significant association between mean (p = 0.0153) and maximum temperature (p = 0.008) on the day of the presentation and abscess incidence was observed. Furthermore, a significant correlation between OA incidence and maximum temperature 2 days before presentation was found (p = 0.034). The deviation of the mean temperature on the day of the presentation from the monthly mean temperature had a significant influence (p = 0.021) on the incidence of OA. In contrast to temperature, atmospheric pressure had no significant influence on the incidence of OA. CONCLUSION: This study supports a relationship between the incidence of odontogenic abscess and outdoor temperature, but not atmospheric pressure. A significantly higher frequency of patients with an OA presented at our emergency department on days with (comparably) low and high outdoor temperatures. Furthermore, a significant correlation between incidence and maximum temperature 2 days before presentation was found. CLINICAL RELEVANCE: The treatment of odontogenic infections has become a significant economic burden to public health care facilities. The results of this study may help to adapt the numbers of doctors/dentists on duty in relation to different weather conditions. In any case, it is an impetus to think outside the box.

[Frequency and management of complex facial fractures-an oral and maxillofacial surgical assessment]. / Häufigkeit und Management von Gesichtsschädelfrakturen ­ eine MKG-chirurgische Einschätzung.

INTRODUCTION: The treatment of facial fractures is an integral part of the oral and maxillofacial surgical treatment spectrum. In the case of complex fractures that involve multiple levels of the facial skeleton associated with severe concomitant injuries, an individual and interdisciplinary treatment approach is needed, which requires the infrastructure of a national trauma center. OBJECTIVE: The aim of this study was to analyze the incidence and management of patients with complex facial fractures and considering the concomitant injury pattern. MATERIAL AND METHODS: A retrospective analysis of patients with complex facial fractures during the years 2009-2015 admitted to the emergency surgical department of a national trauma center was carried out. The identification of appropriate patient cases was based on the International Statistical Classification of Diseases and Related Health Problems (ICD) coding of electronic patient data. Only patients with at least a combination of mandibular and midfacial fractures (2-level fractures) were considered. Patients with mainly dentoalveolar fractures and simple nasal bone fractures were not included. The evaluation of the electronic medical records included the etiology, fracture pattern, associated severe injuries on the basis of the injury severity score (ISS), treatment regimen as well as the length of the hospital stay. RESULTS: In the 7­year study period, 3382 patients were identified with facial fractures. Of these, 128 patients (3.78%) presented with a complex fracture pattern with a combination of mandibular fractures and fractures of the midface. The majority of these patients (n = 92) had less severe concomitant injuries (ISS ≤ 16), while 36 patients showed severe concomitant injuries (ISS > 16). The incidence of a 3-level fracture involving the mandible, midface and anterior skull base was only 0.47% and could be detected in 16 patients, of which 10 were classified as polytrauma (ISS > 16). CONCLUSION: The incidence of complex fractures of the facial skeleton was comparatively low with almost 4%. More than one in four patients with complex injury patterns of the facial skeleton exhibited severe concomitant life-threatening injuries, necessitating an interdisciplinary management with the specialized infrastructure of a nationwide trauma center.

Clinical outcome after orbital floor fracture reduction with special regard to patient's satisfaction.

PURPOSE: Primary reconstruction via transconjunctival approach is a standardized treatment option for orbital floor fractures. The aim of this study was to compare the findings of specific ophthalmologic assessment with the patient's complaints after fracture reduction. METHODS: A retrospective medical chart analysis was performed on patients who had undergone transconjunctival orbital floor fracture reduction for fracture therapy with resorbable foil (ethisorb sheet or polydioxanone foil). A follow-up assessment including ophthalmological evaluation regarding visual acuity (eye chart projector), binocular visual field screening (Bagolini striated glasses test) and diplopia (cover test, Hess screen test) was conducted. Additionally, a questionnaire was performed to assess patients' satisfaction. RESULTS: A total of 53 patients with a mean follow-up of 23 months (ranging from 11 to 72) after surgical therapy were included. Diplopia was present preoperatively in 23 (43.4%) and reduced in follow-up examination (n = 12, 22.6%). Limitations in ocular motility reduced from 37.7% to 7.5%. The questionnaire about the patient's satisfaction revealed excellent outcomes in relation to the functional and esthetical parameters. CONCLUSION: Transconjunctival approach is a safe approach for orbital fracture therapy. Postoperative diplopia is nearly never perceptible for the individual and differs to pathologic findings in the ophthalmic assessment.

Patient-Specific Implant in Prosthetic Craniofacial Reconstruction: First Report of a Novel Technique With Far-Reaching Perspective.

BACKGROUND: Application of endosseous implants in prosthetic craniofacial reconstruction represents a secure and reliable method and is a well-established surgical procedure. In areas of low bone presentation, standardized plate-like titanium implants are available. For allowing a congruent fitting to the recipient site, these contemporary implants have to be manually adapted--implicating drawbacks in terms of time consumption, technical complexity, and insufficient functional outcome. Owing to these limitations, a custom-made patient-specific implant is introduced based on Digital Imaging and Communications in Medicine (DICOM) data and designed for optimal prosthetic reconstruction. METHODS: For the first time, the application of a prefabricated patient-specific implant for retaining a craniofacial prosthesis is described. In a 64-year-old man with partial nasal defect standardized plate-like implants failed because of compromised bone quality due to Osler disease. To realize an implant-retained prosthetic reconstruction, a patient-specific implant was fabricated based on computer-aided design and computer-aided manufacturing (CAD/CAM) technology. This technique allows for considering the implant's ideal geometry as well as its correct placement of the required magnetic abutments. Furthermore, the surface of the implant can be designed for optimal hygienic conditions. RESULTS: The patient-specific implant was successfully inserted in a time effective operating procedure. Follow-up at 6 months showed an excellent functional and aesthetic outcome. CONCLUSIONS: Application of prefabricated patient-specific implants offers prospectively an ideal tool for retaining craniofacial prostheses and should be considered a viable option in standard cases, but obligatory in anatomically demanding defects.

Asymmetric, disproportionate craniofacial hyperostoses of mosaic pattern in a patient not meeting Proteus syndrome criteria.

A 34-year-old patient with asymmetric hyperostosis of the craniofacial skeleton much more pronounced on the right side is presented. A long-term follow-up of 16 years showed progression of overgrowth even after skeletal maturity and despite repeated surgical corrections focusing on regional reduction of the hyperostoses. Clinical situation during infancy, adolescence, and adulthood is documented. Although the craniofacial hyperostosis in the patient was indicative of the Proteus syndrome, the applicable criteria were not met. Proportionate mild hemihypertrophia/hyperplasia of the patient's right extremities also exclude an oligosymptomatic variant of the Proteus syndrome limited to the skull. Both surgical strategies and difficulty of a diagnostic classification are discussed.

Dentoalveolar injury related to general anaesthesia: a 14 years review and a statement from the surgical point of view based on a retrospective analysis of the documentation of a university hospital.

INTRODUCTION: Damage to dentoalveolar structures related to general anaesthesia is a well-known complication and may represent a relevant morbidity for affected patients. Central documentation of perioperative dentoalveolar injuries was performed since 1990 in the Department of Anaesthesiology and Intensive Care Medicine in cooperation with the Department of Oral and Maxillofacial Surgery at the Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum. Documentation of perioperative dentoalveolar injury consisted of anaesthesia charts, reports of the anaesthesiologists and consultant maxillofacial surgeons. MATERIALS AND METHODS: Retrospective analysis of the data from 1990 to 2004 was performed according to this documentation with respect to incidence, matter, distribution of dental injury and therapeutic consequences. RESULTS: Within 14 years 82 'dental injuries' with 103 affected teeth were documented in calculated 375,000 general anaesthesias. Incidence of 0.02% was very constant with an average of 5.5 events/year. Eighty-nine percent of the documented injuries occurred during scheduled operative procedures. Only 32.9% of the injuries took place during endotracheal intubation. In about 50% the injury was not related to intubation or extubation but happened during general anaesthesia. In 80% the dental injury was estimated by the anaesthesiologist as 'not avoidable'. In 83% pre-existing affection or structural injury of intraoral tissues was documented, in 32.7% of the affections sufficient therapy could be provided already during inhospital stay. CONCLUSION: Perioperative dentoalveolar injury is surely an annoying complication of general anaesthesia. However incidence is rare and seems to be unavoidable. Pre-existing damage to dentoalveolar structures is the main risk for additional injuries related to general anaesthesia. Adequate therapy can be provided by interdisciplinary concepts. There should be a fair balance between the benefit of the surgical procedure and the risk of dental injury related to general anaesthesia. Awareness of the problem and proper documentation are important factors for adequate management in liability cases.

Distraction Osteogenesis After Stem Cell Transplantation: A Pioneer Approach.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established therapy and is without alternative for certain groups of patients. Successful HSCT induces both long-lasting remission and tolerance without the need for further immunosuppression. In this case, cellular repair and regenerative processes work in a physiologic manner allowing elective surgical procedures, such as the interdisciplinary correction of dentofacial anomalies. Here, we report the successful management of transverse maxillary deficiency by transpalatal distraction and subsequent orthodontic treatment in a 12-year-old boy who underwent HSCT for high-risk acute lymphoblastic leukemia at 5 years of age.

Sublingual cysts of different entities in an infant - A case report and literature review.

BACKGROUND: Congenital cysts and fistulas of the neck are common in children, often located in the head and neck area. Belonging to the group of tumor-like conditions, dermoid and epidermoid cysts are dysontogenetic lesions with seldom multiple co-occurrences in infants. CASE REPORT: We report on a nine-month-old female with a persisting congenital fistula of the tongue. The patient was admitted with acute poor feeding and hypersalivation, which started within the last 24 h. Magnetic resonance imaging detected a fistula of the tongue connected to sublingual cystic lesions. Intraoral surgical removal of three cystic lesions and the fistula was performed under general anesthesia. Histopathological analysis confirmed the coexistence of an epidermoid cyst and two dermoid cysts. CONCLUSION: Sudden feeding difficulties in combination with dysphagia and tongue displacement in pediatric patients pose an emergency situation that requires prompt diagnostic clarification. A persisting congenital fistula of the tongue is a clear indication of dysontogenetic lesions, including malformations, tumors, and tumor-like lesions. Congenital sublingual cysts are rare in infants, but can be life threatening when present. Surgical excision with histopathological analysis is essential to exclude any form of malignancy and malignant transformation.

Penetrating Foreign Bodies in Head and Neck Trauma: A Surgical Challenge.

Penetrating foreign bodies of different origins in the head and neck are rare and potentially dangerous injuries, which might pose problems for their detection, primary care, and final treatment. Depending on the severity of the underlying trauma, some injuries present a higher risk for the presence of foreign bodies. Minor wounds, including common lacerations, are likely to be contaminated with loose gravel debris or dental fragments, and need to be distinguished from severe wounds caused by impalement, shootings, stabbings, and explosions. Blast injuries resulting from terror attacks are challenging recent therapeutic concepts. Even though these injury patterns are uncommon, they carry the risk of impacted objects with dramatic consequences. Despite improving medical imaging techniques, detection remains a challenge as it is dependent on the material of the foreign body, the affected anatomical site, and the injury severity. Therefore, a detailed history of the circumstances leading to trauma is essential when foreign objects are not visible during clinical examination. Precise detection of the foreign body, its anatomical position, and the affected surrounding structures are vital, especially for impalement injuries of the head and neck area. Therefore, an interdisciplinary planning approach is essential prior to removal of the foreign object. Finally, tension-free anatomical adaptation of the corresponding structures is crucial for maintaining and restoring aesthetic and function. Here, we give an overview of the diagnosis and treatment of cases of foreign body injuries encountered in our department.

Mutation c.943G>T (p.Ala315Ser) in FGFR2 Causing a Mild Phenotype of Crouzon Craniofacial Dysostosis in a Three-Generation Family.

Crouzon syndrome craniofacial dysostosis type I [OMIM 123500] is caused by mutations in the gene encoding fibroblast growth factor receptor-2 (FGFR2). An overlapping phenotype with Muenke and Crouzon syndrome with acanthosis nigricans (FGFR3 mutations) is known. The clinical diagnosis can be corroborated by molecular studies in about 80-90% of the cases. No clear genotype/phenotype correlation has been identified yet. Here, we describe a second family with a mild phenotype in which the FGFR2 mutation c.943G>T leading to the amino acid substitution p.Ala315Ser was detected. Five affected family members showed craniofacial dysostosis without overt craniosynostosis. They all had midface hypoplasia. Crouzonoid appearance with mild protrusion of bulbi was only apparent in our index patient as well as obstructive sleep apnea episodes leading to reduced oxygen saturation; therefore, surgical intervention was suggested. One other affected family member additionally had iris coloboma.

Role of distraction osteogenesis in craniomaxillofacial surgery.

In the field of orthopedic surgery, distraction osteogenesis (DO) is well known for limb lengthening procedures or secondary corrective surgery in the fracture treatment of the extremities. The principle of gradual expansion of bone and surrounding soft tissues as originally described by G.A. Ilizarov is also applicable to the craniofacial skeleton when growth deficiency is present, and the patients affected by craniofacial or dentofacial anomalies may require distraction procedures. The surgical management is comparable. After osteotomy and the mounting of a specific craniomaxillofacial distraction device, active distraction is started after a latency phase of several days, with a distraction rate of up to 1 mm/day until the desired amount of distraction has been achieved. Subsequently, distractors are locked to provide appropriate stability within the distraction zone for callus mineralization during the consolidation phase of 3-6 months, which is followed by a further remodeling of the bony regenerate. After 14 years of clinical application, the role and significance of craniomaxillofacial DO are discussed after reviewing the files of all patients who were treated by craniomaxillofacial distraction procedures.

Contemporary Correction of Dentofacial Anomalies: A Clinical Assessment.

Contemporary computer-assisted technologies can support the surgical team in the treatment of patients affected by dentofacial deformities. Based on own experiences of 350 patients that received orthognathic surgery by the same team from 2007 to 2015, this clinical review is intended to give an overview of the results and risks related to the surgical correction of dentofacial anomalies. Different clinical and technological innovations that can contribute to improve the planning and transfer of corrective dentofacial surgery are discussed as well. However, despite the presence of modern technologies, a patient-specific approach and solid craftsmanship remain the key factors in this elective surgery.

The "tight orbit": Incidence and management of the orbital compartment syndrome.

PURPOSE: The orbital compartment syndrome (OCS) constitutes a severe emergency, requiring immediate clinical diagnosis and surgical decompression. The key symptom is progressive visual impairment caused by an increase in intraorbital pressure, impairing the perfusion of relevant neurovascular and neurosensory structures. Intraorbital bleeding due to trauma and surgical intervention is known to be the main etiological factor. MATERIAL AND METHODS: A retrospective analysis of all patients affected by an OCS between January 1, 2012, and May 31, 2015, was performed. Patients' records were reviewed with regard to etiology, initial ophthalmologic status, fracture pattern, concomitant medication, surgical management, and postoperative outcome. The incidence of OCS was calculated based on the total number of craniomaxillofacial (CMF) emergencies. RESULTS: Within 3.5 years, a total of 18,093 CMF emergencies were registered. In 16 patients, an OCS was documented, corresponding to an incidence of 0.088%. The mean patient age was 67.31 ± 23.86 years, ranging from 22 to 102 years. The etiology varied, but trauma with subsequent intraorbital bleeding was the main cause. The use of anticoagulative medication was documented in 50% of the cases. In 14 patients, immediate surgical orbital decompression was performed: in 10 patients, vision could be preserved; in three patients, blindness resulted; and one patient was lost to follow-up. Two patients were managed without surgery. CONCLUSION: With regard to the total number of CMF emergencies, OCS is a rare condition. Early clinical diagnosis and surgical decompression are required to prevent permanent vision impairment. Anticoagulative medication must be considered as a predisposing factor for an orbital compartment syndrome in patients affected by periorbital trauma.

Callus mineralization following distraction osteogenesis of the mandible monitored by scanning acoustic microscopy (SAM).

BACKGROUND: Scanning acoustic microscopy uses ultrasound to analyse histomorphology of tissues with microscopic resolution and delivers data about physical properties of the specimen. MATERIAL AND METHODS: Bony consolidation was monitored by scanning acoustic microscopy in 12 embedded specimens of dog mandibles after distraction osteogenesis. Increasing mineralization was detected by measurements of acoustic impedance (Z). RESULTS: There was a strong correlation between acoustic impedance and time of consolidation. Measurements of the speed of sound (v) provided specific information about non-mineralized zones of the distracted area. Distribution of density in the distracted area could be reconstructed by using the measurements of acoustic impedance and speed of sound. CONCLUSION: The method seems suitable for studying bone remodelling qualitatively and quantitatively.

Transpalatal distraction for the management of maxillary constriction in pediatric patients.

CONTEXT: The management of severe maxillary constriction can be challenging. For that purpose surgically assisted maxillary expansion by transpalatal distraction (TPD) can typically be recommended after skeletal maturity. However in selected cases bone borne transpalatal distraction devices can contribute to improve maxillary constriction considerably earlier already during mixed dentition. AIMS: To assess the possibility of bone borne transpalatal distraction in pediatric patients. SETTINGS AND DESIGN: Clinical paper. MATERIALS AND METHODS: Since 2010 TPD has been applied to six pediatric patients during mixed dentition when severe maxillary constriction was present and conventional orthodontic widening has already failed. Individually selected devices (Surgitec, Belgium) were inserted in general anaesthesia and distraction was performed according to well known parameters. RESULTS: Maxillary constriction could be improved in all six patients without any drawbacks by bone borne devices during mixed dentition. Skeletal conditions were obviously improved for subsequent orthodontic or orthognathic therapy without functional impairment. Follow-up is up to 36 months after device removal. CONCLUSIONS: Transpalatal Distraction is recommendable in selected pediatric patients if massive growth disturbance is present or has to be expected. TPD allows for individually adapted maxillary expansion by selection and positioning of appropriate devices in combination with intraoperative testing of maxillary movements and controlled bone removal.

Magnetic resonance imaging induced acute midfacial pain - incidental finding of a dislocated dental bur.

PURPOSE: To describe the management of a patient with an initially unnoticed dislocated dental bur in the maxillary sinus that became symptomatic during a magnetic resonance imaging (MRI) scan. MATERIALS AND METHODS: A MRI scan provoked strong midfacial pain in a 31-year-old male patient, who exhibited ambiguous neurologic impairment consistent with multiple sclerosis. Conventional radiography revealed an opaque foreign body in close proximity to the orbital floor that most likely caused the painful symptoms during the MRI. RESULTS: After additional X-ray computed tomography (X-ray CT) scans were performed, a metal dental bur was removed by a combined transconjunctival and transnasal approach under perioperative antibiotic treatment. CONCLUSION: The disappearance of instruments during surgical procedures requires diligent investigation and immediate retrieval.

Incidence and management of severe odontogenic infections-a retrospective analysis from 2004 to 2011.

The management of odontogenic infections is a typical part of the spectrum of maxillofacial surgery. Normally these infections can be managed in a straight forward way however under certain conditions severe and complicated courses can arise which require interdisciplinary treatment including intensive care. A retrospective analysis of all patients affected by an odontogenic infection that received surgical therapy from 2004 to 2011 under stationary conditions was performed. Surgical treatment consisted in incision and drainage of the abscess supported by additional i.v. antibiotic medication in all patients. Detailed analysis of all patients that required postoperative intensive medical care was additionally performed with respect to special risk factors. During 8 years 814 patients affected by odontogenic infections received surgical treatment under stationary conditions representing 4% of all patients that have been treated during that period (n = 18981). In 14 patients (1.7%) intensive medical therapy after surgery was required, one lethal outcome was documented (0.12%). In all of these 14 patients a history of typical risk factors was present. According to these results two patients per week affected by an odontogenic infection required stationary surgical treatment, about two patients per year were likely to require additional intensive medical care. If well-known risk factors are present in patients affected by odontogenic infection appropriate interdisciplinary management should be considered as early as possible.

Anaplastology in times of facial transplantation: Still a reasonable treatment option?

Optimum functional and aesthetic facial reconstruction is still a challenge in patients who suffer from inborn or acquired facial deformity. It is known that functional and aesthetic impairment can result in significant psychosocial strain, leading to the social isolation of patients who are affected by major facial deformities. Microvascular techniques and increasing experience in facial transplantation certainly contribute to better restorative outcomes. However, these technologies also have some drawbacks, limitations and unsolved problems. Extensive facial defects which include several aesthetic units and dentition can be restored by combining dental prostheses and anaplastology, thus providing an adequate functional and aesthetic outcome in selected patients without the drawbacks of major surgical procedures. Referring to some representative patient cases, it is shown how extreme facial disfigurement after oncological surgery can be palliated by combining intraoral dentures with extraoral facial prostheses using individualized treatment and without the need for major reconstructive surgery.