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Objective: p63 is a transcription factor involved in multiple biological functions. In the liver, the TAp63 isoform induces lipid accumulation in hepatocytes. However, the role of liver TAp63 in the progression of metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis is unknown., Methods: We evaluated the hepatic p63 levels in different mouse models of steatohepatitis with fibrosis induced by diet. Next, we used virogenetic approaches to manipulate the expression of TAp63 in adult mice under diet-induced steatohepatitis with fibrosis and characterized the disease condition. Finally, we performed proteomics analysis in mice with overexpression and knockdown of hepatic TAp63., Results: Levels of TAp63, but not of ΔN isoform, are increased in the liver of mice with diet-induced steatohepatitis with fibrosis. Both preventive and interventional strategies for the knockdown of hepatic TAp63 significantly ameliorated diet-induced steatohepatitis with fibrosis in mice fed a methionine- and choline-deficient diet (MCDD) and choline deficient and high fat diet (CDHFD). The overexpression of hepatic TAp63 in mice aggravated the liver condition in mice fed a CDHFD. Proteomic analysis in the liver of these mice revealed alteration in multiple proteins and pathways, such as oxidative phosphorylation, antioxidant activity, peroxisome function and LDL clearance., Conclusions: These results indicate that liver TAp63 plays a critical role in the progression of diet-induced steatohepatitis with fibrosis, and its inhibition ameliorates the disease., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

The p63 protein has pleiotropic functions and, in the liver, participates in the progression of nonalcoholic fatty liver disease (NAFLD). However, its functions in hepatic stellate cells (HSCs) have not yet been explored. TAp63 is induced in HSCs from animal models and patients with liver fibrosis and its levels positively correlate with NAFLD activity score and fibrosis stage. In mice, genetic depletion of TAp63 in HSCs reduces the diet-induced liver fibrosis. In vitro silencing of p63 blunts TGF-β1-induced HSCs activation by reducing mitochondrial respiration and glycolysis, as well as decreasing acetyl CoA carboxylase 1 (ACC1). Ectopic expression of TAp63 induces the activation of HSCs and increases the expression and activity of ACC1 by promoting the transcriptional activity of HER2. Genetic inhibition of both HER2 and ACC1 blunt TAp63-induced activation of HSCs. Thus, TAp63 induces HSC activation by stimulating the HER2-ACC1 axis and participates in the development of liver fibrosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Macrostomia or lateral cleft lip is a rare congenital deformity. In this article we describe a surgical technique of macrostomia repair developed. The objective of this article is to assess the results of our surgical technique and to validate a method for macrostomia surgical result evaluation., Methods: We included retrospectively patients with unilateral and bilateral macrostomia, operated from 1995 to 2014 in our department. First part of the study was a satisfaction questionnaire completed by patients. The second part was subjective evaluation of frontal photography (closed mouth, wide open and smiling) by surgeons and lay people with a questionnaire. Both group completed a second questionnaire within one to six months., Results: Eighteen patients answered the questionnaire. The satisfaction for all patients were considered as very good for 38.9% (n = 7) of patients and good for 44.4% (n = 8). 21 patients were photographed, 5 isolated macrostomia, 13 macrostomia with minor facial asymmetry and 3 with a major asymmetry. Surgeons evaluated the result as very good for isolated macrostomia and good for syndromic macrostomia. Layperson evaluated the result as good in isolated macrostomia and macrostomia with minor facial asymmetry and average with major facial asymmetry. P < 0.0001. The evolution of the results between medical and non-medical assessors in our two questionnaires, were non-significant., Conclusion: In this study, we propose a new methodology to assess commissuroplasty surgical results, with a 3 type of evaluator: patients, surgeons and laypeople. We present a simple surgical technique, that allows good results in syndromic and isolated macrostomia., (Copyright © 2021. Published by Elsevier Masson SAS.)

Central-Andean Ecosystems (between 2000 and 6000 m above sea level (masl) are typical arid-to-semiarid environments suffering from the highest total solar and ultraviolet-B radiation on the planet but displaying numerous salt flats and shallow lakes. Andean microbial ecosystems isolated from these environments are of exceptional biodiversity enduring multiple severe conditions. Furthermore, the polyextremophilic nature of the microbes in such ecosystems indicates the potential for biotechnological applications. Within this context, the study undertaken used genome mining, physiological and microscopical characterization to reveal the multiresistant profile of Nesterenkonia sp. Act20, an actinobacterium isolated from the soil surrounding Lake Socompa, Salta, Argentina (3570 masl). Ultravioet-B, desiccation, and copper assays revealed the strain's exceptional resistance to all these conditions. Act20's genome presented coding sequences involving resistance to antibiotics, low temperatures, ultraviolet radiation, arsenic, nutrient-limiting conditions, osmotic stress, low atmospheric-oxygen pressure, heavy-metal stress, and toxic fluoride and chlorite. Act20 can also synthesize proteins and natural products such as an insecticide, bacterial cellulose, ectoine, bacterial hemoglobin, and even antibiotics like colicin V and aurachin C. We also found numerous enzymes for animal- and vegetal-biomass degradation and applications in other industrial processes. The resilience of Act20 and its biotechnologic potential were thoroughly demonstrated in this work., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Cleft lip and palate is the main craniofacial malformation in France. Many surgical techniques had been described to restore cleft palate. In this study, we evaluate phonation in a homogeneous series of patient with isolated unilateral non-syndromic cleft lip and palate before (and after) alveolar cleft closure, operated according to our surgical protocol., Methods: We included retrospectively 71 patients with isolated non-syndromic unilateral cleft lip and palate (UCLP), operated in our department from 2009 to 2013. All patients underwent the same surgical protocol: modified Millard cheilorhinoplasty (from 5 to 9-month-old); direct hard palatal closure (from 12 to 20-month-old); alveolar cleft closure with cancellous iliac bone graft (from 4 to 6-year-old). The phonation and clinical statute were evaluated before and after alveolar cleft closure. Fistula rate and speech evaluation were recorded., Results: The rate of oronasal fistula was 12.7%. About phonation, 76% and 86% of patients were competent or borderline competent respectively before and after gingivoperiostoplasty., Conclusion: This surgical protocol provided speech results in patients with isolated unilateral non-syndromic cleft lip and palate. The gingivoperiostoplasty improved the speech intelligibility., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This study aimed to evaluate the outcomes following a dynamic orthognathic surgical procedure performed at the end of growth to treat asymmetric maxillomandibular deformities linked to unilateral micrognathia when conventional orthognathic surgery was not feasible. The dynamic orthognathic surgical procedure (DOSP) combined concomitant mandibular distraction osteogenesis with contralateral poorly stabilized sagittal split osteotomy and Le Fort I osteotomy. Cephalometric studies were retrospectively conducted on pre- and postoperative lateral and frontal cephalographs, and maxillomandibular movements were calculated. Outcome scores were computed by both experts and laypersons based on photographic analyses. There was a significant postoperative increase in height of the micrognathic ramus in all patients (n = 12; p = 0.002). The angle between the occlusal cant and horizontal reference plane decreased significantly in all of the patients, as did the angle between the midline sagittal plane and mandibular tilt (p < 0.001). Postoperative outcome scores showed significant improvements in all cases, according to both expert and layperson groups. This procedure allows correction of maxillomandibular asymmetries linked to micrognathia. However, it cannot resolve all the factors participating in facial asymmetry, such as those originating in the oculo-auriculo-ventricular spectrum or complex tumor sequelae, and second-step procedures may be required., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the N -acetylgalactosamine-6-sulfatase ( GALNS ) gene. Skeletal dysplasia and the related clinical features of MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance. Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests. However, no data have demonstrated improvements in bone lesions and bone grow thin MPS IVA after ERT, and there is no correlation between therapeutic efficacy and urine levels of keratan sulfate, which accumulates in MPS IVA patients. Using qualitative and quantitative proteomics approaches, we analyzed leukocyte samples from healthy controls ( n = 6) and from untreated ( n = 5) and ERT-treated ( n = 8, sampled before and after treatment) MPS IVA patients to identify potential biomarkers of disease. Out of 690 proteins identified in leukocytes, we selected a group of proteins that were dysregulated in MPS IVA patients with ERT. From these, we identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: lactotransferrin, coronin 1A, neutral alpha-glucosidase AB, and vitronectin. Further studies of cartilage and bone alterations in MPS IVA will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.

Aim: The aim of the study was to investigate hyoid bone anomalies in patients with Pierre Robin sequence (PRS) compared to the control group, using computed tomography (CT) examination and three-dimensional reconstruction of the hyoid bone and mandible., Methods: A retrospective study was performed of patients between birth and 12 months old with isolated PRS (i-PRS) and syndromic PRS (ni-PRS), who had undergone CT examination, and whose results were compared to the control group of the same age. DICOM data was processed to highlight bone tissue. The mandible and hyoid bones were the main targets of the three-dimensional reconstruction. The study outcomes were the analysis of hyoid bone ossification, volume, and position (distance between hyoid and mandibular symphysis). Univariate and multivariate statistical analyses were performed with α=0.05 as level of significance., Results: The study sample included 29 i-PRS and 21 ni-PRS patients, while 43 infants in the control group. Hyoid ossification was present in 26/50 (52%) PRS patients (14 i-PRS; 12 ni-PRS) but in 31/43 controls (72%). Statistical analysis showed that absence of hyoid ossification was significantly associated with the diagnosis of PRS (P<0.05). Only ni-PRS patients showed a significant reduction of the distance between hyoid and mandible compared to the control group (P<0.001). Hyoid volume was significantly lower only in the ni-PRS group than in controls (P<0.001)., Conclusion: I-PRS and ni-PRS patients differ both etiologically and clinically. Ni-PRS patients confirmed their worst clinical condition than i-PRS with severe anomalies of hyoid development, helping for their ontogeny classification., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Unicystic ameloblastoma (UA), a benign odontogenic tumor of the jaw, represents less than a third of all ameloblastomas and seems less aggressive than other types of ameloblastoma. We present here the first case of UA that developed prenatally and was successfully managed in the early neonatal period with marsupialization and curettage performed carefully to avoid injury to the tooth germ. BRAF and SMO mutations were not detected. After 2 years of follow-up, complete reossification and normal eruption of deciduous teeth were noted, and there was no recurrence of UA. We recommend conservative treatment of UA in the pediatric population to avoid loss of and/or injury to the tooth germ, provided close follow-up is carried out all through the individual's growth for early detection of potential recurrences, growth impairments, or tooth eruption disorders. The intratumoral somatic mutational status of BRAF, SMO, RAS family, and FGFR2 may help determine personalized targeted treatment, particularly in case of recurrence., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To review orofacial disabilities and their consequences in children with Moebius syndrome (MBS)., Method: We retrospectively analysed the records of 32 patients (21 males, 11 females) with non-progressive bilateral facial and abducens palsies who had been examined before 6 months of age., Results: All facial muscles were severely involved in 17 patients; in the 15 others, partial movements were found in the lower face. Most patients (n=24) were unable to smile. Patients frequently presented with congenital trismus (n=20) and drooling (n=18). Additional palsies involved cranial nerves IX and X (n=18) and XII (n=25). Sucking was absent or weak in 30 patients; swallowing was impaired in 25. During the first month of life, feeding disorders were graded as severe/moderate in 25. Respiratory complications occurred in 17. Severe feeding disorders were associated with congenital trismus (p=0.01) and with cranial nerve IX and X palsy (p=0.01). Growth failure between 1 and 6 months of age, followed by catch-up growth between 6 and 12 months, was observed in 20 patients. Between 2 and 5 years of age, 25 out of 32 patients attained normal oral diet and 28 out of 29 showed normal growth., Interpretation: Children with MBS frequently require adjusted therapeutic options to prevent failure to thrive. Congenital trismus, cranial nerve IX and X palsy, and laryngeal-tracheal dysfunctions are predictors of severe feeding disorders., What This Paper Adds: Moebius syndrome frequently induces reduced oral intake and early failure to thrive. Normal oral diet and growth parameters are attained at 2 to 5 years of age. Congenital trismus, pharyngeal palsy, and laryngeal disorders predict dysphagia., (© 2019 Mac Keith Press.)

Residual nasal deformity in patients with cleft palate remains the main demand of these patients. Performing primary nasal surgery has significantly improved the results. However, it is still often necessary to improve the nasal morphology. Respect of tissues during primary surgery is essential and allows easier secondary corrections. Anatomical reconstruction greatly facilitates the treatment of secondary deformities. Do not hesitate in case of major labionasales sequelae, to make revision, according to the rules of primary surgery, of the entire lip and nose., (Copyright © 2019. Published by Elsevier Masson SAS.)

Aim and Scope: Result assessment in cleft surgery is a technical challenge and requires the development of dedicated morphometric tools. Two cohorts of patients managed according to two different protocols were assessed at similar ages and their palatal shape was compared using geometric morphometrics., Material and Methods: Ten patients (protocol No. 1) benefited from early lip closure (1-3 months) and secondary combined soft and hard palate closure (6-9 months); 11 patients (protocol No. 2) benefited from later combined lip and soft palate closure (6 months) followed by hard palate closure (18 months). Cone-Beam Computed Tomography (CBCT) images were acquired at 5 years of age and palatal shapes were compared between protocols No. 1 and No. 2 using geometric morphometrics., Results: Protocols No. 1 and No. 2 had a significantly different timing in their surgical steps but were assessed at a similar age (5 years). The inter-canine distance was significantly narrower in protocol No. 1. Geometric morphometrics showed that the premaxillary region was located more inferiorly in protocol No. 1., Conclusion: Functional approaches to cleft surgery (protocol No. 2) allow obtaining larger inter-canine distances and more anatomical premaxillary positions at 5 years of age when compared to protocols involving early lip closure (protocol No. 1). This is the first study comparing the intermediate results of two cleft management protocols using 3D CBCT data and geometric morphometrics. Similar assessments at the end of puberty are required in order to compare the long-term benefits of functional protocols., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Rare diseases affecting the teeth, the oral cavity and the face are numerous, each of them present specific characteristics, and is a life-long condition. The aim of the study was to assess the association between Oral health-related quality of life (OHRQoL), and demographic characteristics, clinical and dental factors, and psycho-social characteristics to investigate that oral symptoms are not the main factors underlying a decrease in OHRQoL., Material and Methods: We conducted a national cohort study in French centres for rare diseases (RD) specialized in orofacial diseases. The inclusion criteria were: to have received care in RD centres over the last 5 years (2012-2017) and to have been between 6 and 17 years of age on September 1, 2017. Patients were invited to answer a questionnaire composed of socio-demographic, clinical and dental questions, psychosocial questions and then fill in the Child-OIDP Index. At the end of the questionnaire, a free space was left for the patient to add a verbatim comment to provide qualitative data. Thematic analysis was used to analyze the verbatim answers., Results: Complete data were available for 110 patients. The sample included 44.5% boys and 55.5% girls. Ages ranged from 6 to 17 years old and 68.2% were between 6 to 12 years old and 31.8% were between 13 and 17 years old. Factor associated with a lower OHRQoL were: being a girl (p = 0.03), renouncement to dental care for financial reasons (p = 0.01), having syndromic disease (p = 0.01), having a problem with tooth shape and color (p = 0.03), feeling isolated, alone and different from other children (p = 0.003 and p = 0.02). Qualitative analysis highlighted very little recourse to psychological care and patients reported great anxiety and fear about the future., Conclusion: OHRQoL of children suffering from these diseases is impaired, especially from the psychosocial point of view but also from that of the course of treatment and access to care. There is a need to improve the legibility of care pathways and the financial coverage of treatments.

Pai syndrome was originally described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present with the full triad, and most exhibit a wide spectrum of phenotypic variability. The aim of this study was to phenotypically delineate Pai syndrome and to propose new criteria to facilitate a clinical diagnosis in the future. The study cohort consisted of seven case patients and an additional 60 cases diagnosed with Pai syndrome identified in a literature review. Only 23 of 67 patients presented the full triad as historically described by Pai et al. (1987). A congenital facial midline skin mass was always encountered, particularly affecting the nasal structures (60/67). A midline facial cleft was reported in 45 of 67 patients and a pericallosal lipoma in 42 of 67 patients. The proposed definition of Pai syndrome is the association of (1) a congenital nasal and/or mediofrontal skin mass and/or a mid-anterior alveolar process polyp as a mandatory criterion, and at least one of the following criteria: (2) midline cleft lip and/or midline alveolar cleft, and/or (3) a pericallosal lipoma or interhemispheric lipoma in the case of corpus callosum dysgenesis., (Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

"High-altitude Andean Lakes" (HAAL) are pristine environments harboring poly-extremophilic microbes that show combined adaptations to physical and chemical stress such as large daily ambient thermal amplitude, extreme solar radiation levels, intense dryness, alkalinity, high concentrations of arsenic (up to 200 ppm) and dissolved salts. In this work, we compared the UV resistance profiles, pigment content and photoreactivation abilities of three UV-resistant bacteria isolated from distinct niches from HAALs, that is Acinetobacter sp. Ver3 (water, Lake Verde; 4400 m), Exiguobacterium sp. S17 (stromatolite, Lake Socompa, 3570 m) and Nesterenkonia sp. Act20 (soil, Lake Socompa, 3570 m). UV resistance ability of HAAL's strains indicate a clear adaptation to high radiation exposure encountered in their original habitat, which can be explained by genetic and physiological mechanisms named as the UV-resistome. Thus, the UV-resistome depends on the expression of a diverse set of genes devoted to evading or repairing the damage it provoked direct or indirectly. As pigment extraction and photoreactive assays indicate the presence of photoactive molecules, we characterized more in detail proteins with homology to photolyases/cryptochromes members (CPF). Phylogenetic analyses, sequence comparison and 3D modeling with bona fide CPF members were used to prove the presence of functional domains and key residues in the novel proteins., (© 2018 The American Society of Photobiology.)

Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and glossoptosis with those of respiratory and feeding disorders, we retrospectively studied a series of 50 infants with retrognathia, glossoptosis, cleft palate, and airway obstruction. The patients were managed from birth to at least 6 years of age by a single pediatric team at the Armand Trousseau Hospital in Paris within a 12 years period (2000-2012). Retrognathia and glossoptosis were graded in the neonatal period according to a specific clinical examination. Ventilation assistance was required for 32/50 (64%) patients, and enteral feeding for 41/50 (82%). The grades of retrognathia and glossoptosis and the severity of respiratory disorders did not differ between patients with isolated PRS and syndromic PRS. Severe respiratory disorders were more common and long-lasting feeding (>12 months) was more frequently required in patients with syndromic PRS compared with isolated PRS (42 vs. 13%, p = 0.04 and 42 vs. 4%, p < 0.01 respectively). Using univariate analysis, neurological impairments and laryngomalacia were associated with severe respiratory disorders [Odds ratio (OR) 5.0, 95% CI 1.3-19.6; and OR 14.6, 95% CI 1.3-161.4; p < 0.05] as well as with long-lasting feeding (>12 months) disorders (OR 18.6, 95% CI 3.9-89.2 and OR 20.4, 95% CI 3,4-122.8; p < 10 -2 ). Syndromic SPR status was also associated with severe respiratory disorders (OR 4.9, 95% CI 1-32.5; p < 0.05). Using multivariate analysis, only syndromic PRS status was predictive for severe respiratory disorders (adjusted OR 8, 95% CI 1.47-44.57; p < 0.05); and only neurological impairments remained a significant risk for long lasting feeding disorders (>12 months) (adjusted OR 21.72, 95% CI 3.4-138.63; p < 10 -2 ). The grades of retrognathia and glossoptosis were not predictive factors for the severity of respiratory and feeding disorders. Conclusion : In children with PRS, the severity of clinical conditions may not correlate with anatomic variables but rather with laryngeal abnormalities, neurological impairement and syndromic PRS status.

Pierre Robin syndrome (PRS) is characterized of a triad of clinical signs: micrognathia, glossoptosis and obstruction of the upper airways frequently associated with palatal cleft. It is a heterogenic pathological entity and it can be found as isolated disease (nsPRS) or in association with other syndromes (sPRS), with more pronounced symptoms and systemic involvement. This review aims to summarize the principal features of PRS, analysing the different aspects of the disease. Epidemiological data highlight incidence, severity and mortality of PRS; pathophysiological mechanism reports the etiology and pathogenesis of the disease distinguishing between isolated and syndromic form. Because of the clinical importance of PRS, it's fundamental to describe the features of the Robin sequence to clearly define its primary and secondary clinical signs useful to diagnosis. A complete evaluation of the syndrome allows choosing the most appropriate therapeutic treatment, opting for conservative or surgical management, in order to improve the quality of life of the patient., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Cross-linked hyaluronic acid-based fillers have gained rapid acceptance for treating facial wrinkles, deep tissue folds and sunken areas due to aging. This study evaluates, in addition to space-filling properties, their effects on softness and elasticity as a secondary effect, following injection of 3 commercially available cross-linked hyaluronic acid-based fillers (15mg/mL, 17,5mg/mL and 20mg/mL) in patients presenting with congenital or acquired facial malformations., Patients Et Methods: We started injecting gels of cross-linked hyaluronic acid-based fillers in those cases in 2013; we performed 46 sessions of injections in 32 patients, aged from 13-32. Clinical assessment was performed by the patient himself and by a plastic surgeon, 15 days after injections and 6-18 months later., Results: Cross-linked hyaluronic acid-based fillers offered very subtle cosmetic results and supplemented surgery with a very high level of satisfaction of the patients. When injected in fibrosis, the first session enhanced softness and elasticity; the second session enhanced the volume. Cross-linked hyaluronic acid-based fillers fill sunken areas and better softness and elasticity of scar tissues., Conclusion: In addition to their well-understood space-filling function, as a secondary effect, the authors demonstrate that cross-linked hyaluronic acid-based fillers improve softness and elasticity of scarring tissues. Many experimental studies support our observations, showing that cross-linked hyaluronic acid stimulates the production of several extra-cellular matrix components, including dermal collagen and elastin., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Comparing functional outcomes after velar repair appeared to be difficult because of the absence of international standardized scale. Moreover most of the studies evaluating speech after cleft surgery present multiple biases. The aim of our study was to assess speech outcomes in a homogeneous group of patients, and to define an equivalence table between different speech scales., Materials and Methods: Patients with isolated cleft lip and palate (CLP), operated in our unit by the same senior surgeon were included. All patient were operated according to the same protocol (cheilo-rhinoplasty and intravelar veloplasty at 6 months, followed by a direct closure of the hard palate at 15 months). Speech evaluation was performed after 3 year-old and before the alveolar cleft repair. Borel-Maisonny scale and nasometry were used for speech evaluation., Results: Twenty-four patients were included: 17 unilateral CLP and 7 bilateral CLP. According to the Borel-Maisonny classifications, 82.5% were ranged phonation 1, 1-2 or 2b. Nasometry were normal in almost 60% of cases., Conclusions: This study showed the efficiency of our protocol, and intravelar veloplasty. Moreover we proposed an equivalence table for speech evaluation scale., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Backgound: Pierre Robin sequence (PRS) has worse speech outcomes than isolated cleft palate. We aimed to search for possible associations of phonological outcomes with PRS status (isolated vs syndromic), clinical severity, soft palate muscles deficiency, or surgical procedure., Methods: We designed a retrospective study of 130 children (male/female ratio: 0.4) with isolated (96) or syndromic (34) PRS with cleft palate. Grading systems were used to classify retrognathia, glossoptosis, and respiratory and feeding disorders. Electromyography was used to investigate levator veli palatini muscles. Hard cleft palate was measured using maxillary casts. Intravelar veloplasty was performed using the Sommerlad's technique. Phonological outcomes were assessed using the Borel-Maisonny classification., Results: Cleft palate was repaired in one stage (65.5%) or hard palate closure was postponed (34.5%). Velopharyngeal insufficiency was more frequent in syndromic PRS (53%) vs. isolated PRS (30.5%) (p = 0.01), but was not statistically associated with clinical grade, hard cleft palate width, soft palate electromyography, and surgical procedure., Conclusions: In children with PRS, anatomic variables, initial clinical severity, and soft palate muscle deficiency are not predictors of speech prognosis., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: We designed a retrospective study of 59 patients with congenital sporadic nonprogressive bilateral facial and abducens palsies., Methods: Examinations included needle electromyography (EMG) of facial and oral muscles, facial nerve motor latency and conduction velocity (FNCV), and blink responses (BR)., Results: Neurogenic EMG changes were found in 1 or more muscles in 55 of 59 patients, with no abnormal spontaneous activity. EMG changes were homogeneously neurogenic in 17 patients, homogeneously myopathic in 1 patient, and heterogeneous in 41 of 59 patients. Motor latency was increased according to recordings from 52 of 137 facial muscles. An increase of motor latency was not associated with neurogenic EMG (Fischer's test: right, P = 1; left, P = 0.76). FNCV was slowed in 19 of 36 patients. BR was absent bilaterally in 35 of 58 patients; when present, R1 and R2 latencies were normal., Discussion: Our results support the hypothesis of an early developmental defect localized in motor cranial nerves with spared V-VII internuclear pathways. Muscle Nerve, 2018., (© 2018 Wiley Periodicals, Inc.)

Background: In the last ten years, national rare disease networks have been established in France, including national centres of expertise and regional ones, with storage of patient data in a bioinformatics tool. The aim was to contribute to the development and evaluation of health strategies to improve the management of patients with rare diseases. The objective of this study has been to provide the first national-level data concerning rare diseases of the head, neck and teeth and to assess the balance between demand and supply of care in France., Methods: Centres of expertise for rare diseases record a minimum data set on their clinical cases, using a list of rare Head, Neck and Teeth diseases established in 2006. The present analysis focuses on 2008 to 2015 data based on the Orphanet nomenclature. Each rare disease RD "case" was defined by status "affected" and by the degree of diagnostic certainty, encoded as: confirmed, probable or non-classifiable. Analysed parameters, presented with their 95% confidence intervals using a Poisson model, were the following: time and age at diagnosis, proportions of crude and standardized RD prevalence by age, gender and geographical site. The criteria studied were the proportions of patients in Paris Region and the "included cases geography", in which these proportions were projected onto the other French Regions, adjusting for local populations., Results: In Paris Region, estimated prevalence of these diseases was 5.58 per 10,000 inhabitants (95% CI 4.3-7.1). At December 31st 2015, 11,342 patients were referenced in total in France, of whom 7294 were in Paris Region. More than 580 individual clinical entities (ORPHA code) were identified with their respective frequencies. Most abnormalities were diagnosed antenatally. Nearly 80% of patients recorded come to Paris hospitals to obtain either diagnosis, care or follow up. We observed that the rarer the disease, the more patients were referred to Paris hospitals., Conclusions: A health network covering a range of aspects of the rare diseases problematic from diagnostics to research has been developed in France. Despite this, there is still a noticeable imbalance between health care supply and demand in this area.

Background/objectives: Temporalis muscle lengthening myoplasty improves tightening of the lips and rehabilitates smile for patients with congenital facial palsies. Because Moebius syndrome is heterogeneous, a careful evaluation is mandatory before deciding to perform myoplasty. This series shows the role of electromyography for investigating temporalis muscle and trigeminal nerve motor functions., Methods: We conducted a retrospective study of 18 patients with no upward movements of the labial commissure and absent or unsightly smile. Electromyography was used to study the temporalis muscle bilaterally. Analysis focused on the recruitment pattern of voluntary contraction and electrical silence or activity at rest. Traces were classified as normal, neurogenic, or low-amplitude. Functional outcomes of myoplasty were evaluated by measuring the upward movement of the commissure (mm), and qualified as high (≥10), medium (>5), or little (≤5)., Results: Surgery was cancelled for 5 patients with abnormal electromyographic signs, neurogenic (2) or low-amplitude (3). Myoplasty was performed in 7 patients (age: 8-17 years), unilaterally (3) or bilaterally (4). Preoperative electromyogram was normal (3), or showed moderate neurogenic (2) or low-amplitude (2) changes. Follow-up period after surgery was from 2 to 12 years; functional outcomes were high (5), medium (1), or little (1)., Conclusion: Electromyographic study of the temporalis can detect muscle denervation or atrophy, or dyspraxia, and guide decision to encourage or discourage performing myoplasty, or enhance rehabilitation programme and make the patient aware of possibly modest outcome., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Subcondylar fractures are common in children. Occlusion disorders resulting from these fractures in deciduous or mixed dentition do not have as much impact as in adults due to alveolar adaption possibilities. Functional treatment allows for good functional results, but does not treat the dynamic shortening of the ramus. The objective of this study was to evaluate the axiographic condylar slope changes after subcondylar fracture in children., Materials and Methods: A prospective study was conducted from 2010 to 2015, including all the under-18 patients presenting with a subcondylar fracture. Examination by mean of a Quick Axis axiograph measured the length of propulsion and the condylar inclination on both sides. The main evaluation criterion was the amount of condylar inclination decrease on the fractured side., Results: Twelve patients (mean age: 10.42; 5-16) were included. Eleven children had a loss of condylar inclination on the fractured side without occlusion disorders at 33.2 months on average (3-144 months) after the initial trauma. Only one patient had symmetric axiographies without loss of condylar inclination on the fractured side., Discussion: Dynamic shortening of the ramus on the side of the subcondylar fracture is consistent at short and medium terms in children. Surgical treatment may be the solution for avoiding this dynamic disorder of the mandible and should be evaluated., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Facial traumas are common in children but often unconsidered. Facial injury is responsible of impressive bleeding because of the rich vascularization of the face; this bleeding is often underestimated because of the immediate arterial vasoconstriction that is very strong for children. The blood volume is 80ml/kg for a newborn, with a total of 250ml, reaching 70ml/kg at one year of age. The evaluation must be rigorously performed due to the risk of a sudden decompensation. Regarding the wounds, the primary repair must be performed directly neat or optimal in case of damaged tissues. The rule is to keep maximum of the integrity and to limit debridement. Careful repair often requires general anesthesia, especially in young children, to facilitate a perfect joining of the edges and of the mucocutaneous lines. Losses of substance should be treated by directed cicatrization. Flaps are never performed in children as a first intention for reasons developed below. Given the elasticity of the facial skeleton, fractures require a brutal shock to occur, but the clinical signs can be misleading. For instance, too specific and sometimes ignored, fractures can show weakly symptomatic signs : the fractures of the condylar and the orbital floor, with their respective complication that are temporomandibular bone ankylosis and definitive diplopia. Possible children abuse should be suspected in case of different age lesions and discrepancies between the told story and types of injuries. Once the vital urgency is eliminated, the orbital emergency should be first considered in facial traumas within the ophthalmology specialty because wounds and contusions of the globe are often under-evaluated and threaten the vision. The second emergency is the orbital floor fracture in its 'trapdoor' type, specific to the child. Combined with a motionless eye and uncontrollable vomiting, this is the second true urgency because it involves the prognosis of the oculomotricity and requires emergency surgery. Finally, dental trauma should not be overlooked because of their functional and aesthetic consequences. Primary cicatrization is usually rapid but scars remain inflammatory during a long time. The risk of hypertrophy exists in case of contusions and lacerations associated with wounds but also during puberty and in some locations. Age interfere with the result because growth will either improve or worsen the initial result, depending on the location and mechanism. The secondary specialized and prolonged managing and monitoring is capital on the functional, aesthetic and psychological points of view., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: In 2005, face transplantation ceased to be fiction and became a scientific reality. Today, 10 teams from six different countries have performed 32 face transplantations. Immunosuppressive treatments are similar to other solid organ transplants, and patients have experienced a significant functional improvement. The authors are logically considering expanding face transplantation to children; however, children are not simply small adults., Methods: The authors searched for pediatric patients in need of restoration of fundamental functions of the face, such as orbicularis oris or oculi muscle closure by, first, selecting cases from a pediatric plastic surgery reference center and, second, analyzing the feasibility of face transplantation in those patients. The authors then identified the specific problems that they would encounter during a pediatric face transplant. The authors identified three potential candidates for pediatric face transplantation., Results: Children's youth imposes additional ethical and psychological considerations, such as the balance of risk to benefit when it is quality of life, not life itself, that is at stake; the process of informed consent; the selection process; and the protection of privacy against media exposure. The question becomes not whether children should be included as candidates for face transplantation but whether any ethical barriers should preclude children as candidates for a full face transplant., Conclusion: After careful consideration of the physical, psychological, and ethical aspects of such a procedure, the authors found no such barrier that would either disqualify such vulnerable subjects as profoundly disfigured children or conflict with their best interests.

Root associated bacteria are critical for plant growth and health. Understanding the composition and role of root microbiota is crucial toward agricultural practices that are less dependent on chemical fertilization, which has known negative effects on the environment and human health. Here we analyzed the root-associated microbiomes of soybean and wheat under agricultural field conditions. We took samples from 11 different production fields across a large geographic area. We used 16S rRNA pyrosequencing to explore root microbial communities and also obtained 2,007 bacterial isolates from rhizospheres, which were tested for the presence of plant growth promoting (PGP) traits in-vitro. We observed that pH and nitrate content correlated with beta diversity variability of rhizospheric bacterial communities despite the variable field conditions. We described the dominant bacterial groups associated to roots from both crops at a large geographic scale and we found that a high proportion of them (60-70%) showed more than 97% similarity to bacteria from the isolated collection. Moreover, we observed that 55% of the screened isolates presented PGP activities in vitro. These results are a significant step forward in understanding crop-associated microbiomes and suggest that new directions can be taken to promote crop growth and health by modulating root microbiomes.

Introduction: The incidence of congenital nevi is one over 20,000 newborns per year, 14 % of them are located in the head and neck area. Nevi of the orbital region are particularly difficult to handle on the aesthetic and functional side. The objectives of this study were to conduct an analysis of different clinical presentations of congenital nevi of the eyelid orbital region in children to establish a treatment algorithm., Materiel and Methods: We realised a bi-centric retrospective study including 51 children with orbito-palpebral congenital nevi. We analysed the different clinical presentations, their treatments and their results., Results: Nineteen underwent direct suture excision; three a total skin graft; 15 a combination of treatments, among them four underwent tissular expansion and 14 patients were not operated and clinically followed-up. The average follow-up time was 6.6 years. In 33 cases residual nevic area was still present. The postoperative sequelae were: dyschromia (n=17), anatomical deformation of the eye (n=10), nevi outbreaks (n=8), internal canthus deformation (n=5) and ectropion (n=1)., Conclusion: The results of our study show that therapeutic abstention is preferred when the aesthetic wrong is accepted by the patient and when there is not a higher risk of malignant degeneration. In order to minimise the risk of postoperative sequelae, we propose a therapeutic algorithm for the management of congenital orbital nevi., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Cleft surgery is marked by all the controversies and the multiplication of protocols, as it has been shown by the Eurocleft study. The objective of this pilot study is to start a comparison and analyzing procedure between primary surgical protocols in French centers., Methods: Four French centers with different primary surgical protocols for cleft lip and palate repair, have accepted to be involved in this retrospective study. In each center, 20 consecutive patients with complete cleft lip and palate (10 UCLP, 10 BCLP per center), non syndromic, have been evaluated at a mean age of 5 [range, 4-6]. In this second part, maxillary growth and palatine morphology were assessed on clinical examination and on dental casts (Goslon score). Speech was also evaluated clinically (Borel-maisonny classification) and by Aerophonoscope., Results: Veau-Wardill-Killner palatoplasty involves a higher rate of transversal maxillary deficiency and retromaxillary. The fistula rate is statistically lower with tibial periosteum graft hard palate closure but this technique seems to give retromaxillary. Malek and Talmant two-stage-palatoplasty techniques reach Goslon scores of 1 or 2. Considering speech, Sommerlad intravelar veloplasty got higher outcomes., Conclusions: Primary results. Extension to other centers required. The two-stage palatoplasty, including a Sommerlad intravelar veloplasty seems to have the less negative impact on maxillary growth, and to give good speech outcomes., Level of Evidence: Therapeutic study. Level III/retrospective multicenter comparative study., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Arsenic metabolism is proposed to be an ancient mechanism in microbial life. Different bacteria and archaea use detoxification processes to grow under high arsenic concentration. Some of them are also able to use arsenic as a bioenergetic substrate in either anaerobic arsenate respiration or chemolithotrophic growth on arsenite. However, among the archaea, bioenergetic arsenic metabolism has only been found in the Crenarchaeota phylum. Here we report the discovery of haloarchaea (Euryarchaeota phylum) biofilms forming under the extreme environmental conditions such as high salinity, pH and arsenic concentration at 4589 m above sea level inside a volcano crater in Diamante Lake, Argentina. Metagenomic analyses revealed a surprisingly high abundance of genes used for arsenite oxidation (aioBA) and respiratory arsenate reduction (arrCBA) suggesting that these haloarchaea use arsenic compounds as bioenergetics substrates. We showed that several haloarchaea species, not only from this study, have all genes required for these bioenergetic processes. The phylogenetic analysis of aioA showed that haloarchaea sequences cluster in a novel and monophyletic group, suggesting that the origin of arsenic metabolism in haloarchaea is ancient. Our results also suggest that arsenite chemolithotrophy likely emerged within the archaeal lineage. Our results give a broad new perspective on the haloarchaea metabolism and shed light on the evolutionary history of arsenic bioenergetics.

The human microbiota is the collection of microorganisms living in or on the human body. An imbalance or dysbiosis in these microbial communities can be associated with a wide variety of human diseases (Petersen and Round, 2014; Pham and Lawley, 2014; Zaura et al., 2014). Moreover, when the microbiota of the same body sites is compared between different healthy individuals, specific microbial community features are apparent (Li et al., 2012; Yatsunenko et al., 2012; Oh et al., 2014; Relman, 2015). In addition, specific selective pressures are found at distinct body sites leading to different patterns in microbial community structure and composition (Costello et al., 2009; Consortium, 2012b; Zhou et al., 2013). Because of these natural variations, a comprehensive characterization of the healthy microbiota is critical for predicting alterations related to diseases. This characterization should be based on a broad healthy population over time, geography, and culture (Yatsunenko et al., 2012; Shetty et al., 2013; Leung et al., 2015; Ross et al., 2015). The study of healthy individuals representing different ages, cultural traditions, and ethnic origins will enable to understand how the associated microbiota varies between populations and respond to different lifestyles. It is important to address these natural variations in order to later detect variations related to disease.

Background and Objective: Neonatal bulbar weakness (BW) has various etiologies and a broad prognostic range. We aimed to report outcomes in a large series of children with neonatal BW and explore the association of orofacial electrodiagnostic data with outcome., Methods: We retrospectively reviewed the files of children who presented with facial, lingual, laryngeal, or pharyngeal weakness at birth and who underwent electrodiagnostic studies combining conventional needle electromyography (EMG) of orofacial muscles, blink responses, and EMG during bottle-feeding. Outcome measures included the need for prolonged respiratory assistance and enteral feeding, as well as sensorimotor and cognitive impairments., Results: Of 175 patients, 73% had developmental disorders, 25% suffered from acquired brain damage, and 2% had no apparent underlying disorders. Motor or mental impairment was observed in 71%; death occurred in 16%. Outcomes were not significantly different when comparing developmental disorders versus acquired brain damage or neurogenic versus normal detection EMG. Abnormal blink responses were associated with higher frequencies of respiratory assistance (P = .03), gastrostomy (P = .025), and death (P = .009); moderate or severe oropharyngeal incoordinations were associated with higher frequencies of respiratory assistance (P = .006), prolonged enteral feeding (P < .0001), and gastrostomy (P = .0002)., Conclusions: Orofacial electrodiagnostic studies provide supplementary information to help the pediatrician anticipate the management and prognosis of young infants with BW., (Copyright © 2016 by the American Academy of Pediatrics.)

Background and Purpose: Cleft surgery is marked by all the controversies and the multiplication of protocols, as it has been shown by the Eurocleft study. The objective of this pilot study is to start a comparison and analyzing procedure between primary surgical protocols in French centers., Methods: Four French centers with different primary surgical protocols for cleft lip and palate repair, have accepted to be involved in this retrospective study. In each center, 20 consecutive patients with complete cleft lip and palate (10 UCLP and 10 BCLP per center), non syndromic, have been evaluated at a mean age of 5 [4,6]. In this first part, the aesthetic results of nose and lip repair were assessed based on the scale established by Mortier et al. (1997)., Results: Considering nose outcome, primary cleft repair surgery including a nasal dissection gives a statistically significant benefit in terms of septum deviation. Considering lip result, muscular dehiscence rate is significantly higher in BCLP patients with a two-stage lip closure. The centers using Millard one-stage lip closure do not have uniform results. For UCLP patients, the quality of scar is not statistically different between Skoog and Millard techniques., Conclusions: Primary results based on a simple, reproducible evaluation protocol. Extension to other centers required., Level of Evidence: Therapeutic study. Level III/retrospective multicenter comparative study., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to assess diagnoses and outcomes of infants with 2 or more cranial neuropathies identified using orofacial electromyography (EMG)., Methods: This retrospective study involved 90 patients. Diagnoses took into account clinical, radiological, and genetic data. EMG examined the orbicularis oculi, genioglossus, and levator veli palatini muscles, and blink responses. To evaluate outcome, neurological disability, respiratory complications, and feeding difficulties were recorded., Results: The patients had malformation syndromes (59), encephalopathies (29), or no underlying disorders (2). Neurogenic EMG signs were detected in a mean of 4 muscles, reflecting a mean of 3 affected nerves. EMG identified a higher number of neuropathies than clinical examination alone (82 vs. 31, facial; 56 vs. 2, pharyngeal; 25 vs. 3, hypoglossal). Poor outcome and death were more frequent when EMG identified ≥4 affected nerves (P = 0.02)., Conclusion: EMG highlights multiple cranial neuropathies that can be clinically silent in infants with malformation syndromes or encephalopathies., (© 2015 Wiley Periodicals, Inc.)

Primary alveolar cleft repair has two main purposes: to restore normal morphology and normal function. Gingivoperiosteoplasty with bone grafting in mixed dentition has been a well-established procedure. We hypothesized that 1) performance of this surgery in deciduous dentition would provide favorable bone graft osseointegration, and 2) would improve the support of incisor teeth eruption, thereby avoiding maxillary growth disturbances. We conducted a retrospective study of clinical and tridimensional radiological data for 73 patients with alveolar clefts (with or without lip and palate clefts) who underwent gingivoperiosteoplasty with iliac bone graft in deciduous dentition. Pre- and post-operative Cone Beam Computed Tomography (CBCT) comparison allowed evaluation of the ratio between bone graft volume and initial cleft volume (BGV/ICV ratio), and measurement of central incisor teeth movements. This series of 73 patients included 44 males and 29 females, with a mean age of 5.5 years. Few complications were observed. Post-operative CBCT was performed at 7.4 months. The mean BGV/ICV ratio was 0.62. Axial rotation was significantly improved post-operatively (p = 0.004). Gingivoperiosteoplasty with iliac bone graft is safe when performed in deciduous dentition and results in a sufficient bone graft volume to support lateral incisor eruption and upper central incisor tooth position improvement., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The literature is rich in case reports of intraosseous haemangioma, although most of these are actually cases of venous or capillary malformations. To illustrate this confusion in terminology, we present three cases of slow-flow vascular malformations misnamed as intraosseous haemangioma. A retrospective study of children diagnosed with intraosseous haemangioma was conducted. Clinical and radiological data were evaluated. Histopathological examinations and immunohistochemical studies were redone by three independent pathologists to classify the lesions according to the International Society for the Study of Vascular Anomalies (ISSVA) and World Health Organization (WHO) classifications. Three children who had presented with jaw haemangiomas were identified. Computed tomography scan patterns were not specific. All tumours were GLUT-1-negative and D2-40-negative. The lesions were classified as central haemangiomas according to the WHO, and as slow-flow malformations according to the ISSVA. The classification of vascular anomalies is based on clinical, radiological, and histological differences between vascular tumours and malformations. Based on this classification, the evolution of the lesion can be predicted and adequate treatment applied. The binary ISSVA classification is widely accepted and should be applied for all vascular lesions., (Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function.

Dysmorphogenesis of the mandible complicates assessment of the course of the inferior alveolar nerve in patients with craniofacial microsomia. Our aim in the present study was to correlate the anatomical description of the course with the Pruzansky classification (which indicates the severity of hemifacial microsomia), in the mandibles of 22 affected patients using 3-dimensional computed tomography (CT). We measured the distance between fixed landmarks on the normal and the microsomic sides. The normal sides served as controls. In the group of five patients with type I disease, we found no significant differences between the unaffected and the microsomic side. In the nine patients with Pruzansky type II disease morphological views of the course showed a between-side difference in the length of the bony canal and the height of the mandibular ramus. In the five patients with Pruzansky type III disease, there was no bony canal. Three-dimensional CT analysis may be of value in plotting the course of the inferior alveolar nerve and assisting the surgeon in mandibular osteotomy or distraction osteogenesis., (Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement. Cherubism is caused by gain-of-function mutations in the SH3BP2 gene, leading to overactivation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-dependent osteoclastogenesis. Recent findings in human and mouse cherubism have suggested that calcineurin inhibitors might be drug candidates in cherubism medical treatment. A 4-year-old boy with aggressive cherubism was treated with the calcineurin inhibitor tacrolimus for 1 year, and clinical, radiological, and molecular data were obtained. Immunohistologic analysis was performed to compare preoperative and postoperative NFATc1 staining and tartrate resistant acid phosphatase (TRAP) activity. Real-time PCR was performed to analyze the relative expression levels of OPG and RANKL. After tacrolimus therapy, the patient showed significant clinical improvement, including stabilization of jaw size and intraosseous osteogenesis. Immunohistologic analyses on granuloma showed that tacrolimus caused a significant reduction in the number of TRAP-positive osteoclasts and NFATc1 nuclear staining in multinucleated giant cells. Molecular analysis showed that tacrolimus treatment also resulted in increased OPG expression. We present the first case of effective medical therapy in cherubism. Tacrolimus enhanced bone formation by stimulating osteogenesis and inhibiting osteoclastogenesis., (© 2014 American Society for Bone and Mineral Research.)

Orbitopalpebral anomalies in mandibulofacial dysostosis (Treacher-Collins syndrome) can be difficult to correct surgically and most authors recommend correction of the malar bone after the age of 8 years. We propose a new, early surgical approach for periorbital defects that involves initial implantation of autologous fat and subperiosteal malar lift with a pedicled upper eyelid flap. We prospectively studied 5 children, 3 of whom had previously had orbital reconstruction. Initial fat graft into the periorbital area was followed by a subperiosteal malar lift with lateral canthopexy, and a pedicled upper eyelid flap if needed. Two surgeons independently assessed the patients' characteristics including scleral show before and after operation, antimongoloid palpebral fissures, canthal dystopia, number 6 cleft (Tessier classification), skin quality, and surgical and ophthalmic complications. Before operation 3 patients had had ophthalmic problems. Postoperative evaluation showed improvements in scleral show, canthal dystopia, and skin quality, and correction of antimongoloid palpebral fissures and subcutaneous number 6 clefts. There were no postoperative complications. The proposed protocol gave satisfactory aesthetic and functional results in children with Treacher-Collins syndrome. We recommend that it is considered for periorbital reconstruction in all patients with a mandibulofacial deformity., (Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)