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Background/aim: Hemifacial microsomia (HFM) is the second most common congenital anomaly of the craniomaxillofacial region after the cleft lip and palate. This malformation is characterized by unilateral mandible and ear hypoplasia. Treatment varies and depends on different phenotypes. Severe deficiencies require multiple reconstructive surgeries to address facial asymmetries. This study aimed to review the surgical approach and evaluate the postoperative results of a case with right hemifacial microsomia and anotia., Case Report: This is the case of a 35-year-old female patient who, after multiple graft operations in the right mandible due to hemifacial microsomia, was operated for auricle reconstruction. Initially, a three-dimensional custom made Medpor (porex) was used, covered by the superficial temporal fascia. Subsequently, due to inflammation and partial exposure of this porous polyethylene implant (PPI), a temporalis muscular flap along with the deep temporal fascia were used as a salvage operation. Ten months later, the patient underwent deep plane face lift combined with open rhinoplasty. Lefort I osteotomies and transoral lip lengthening through a transection of the levator nasi septi muscle were also performed. Ear helix reconstruction was completed with a rotation scalp flap after tissue expansion. The patient had an uncomplicated postoperative course with an aesthetically acceptable result., Conclusion: As a congenital disorder, hemifacial microsomia is present at birth and successful reconstruction is of fundamental importance for the smooth integration of these individuals into society. The multiple asymmetries, the affected topographic area of the face, as well as the onset in neonatal age constitute a challenge for reconstructive surgery., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P. VPD was significantly more prevalent in CFM with CL/P than in CFM without CL/P (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.9-8.7; P < 0.001). Multivariate logistic regression showed a significant association between CL/P and VPD in CFM patients (OR 7.4, 95% CI 2.1-26.3; P = 0.002). The presence of VPD was not associated with sex, the laterality or severity of CFM. Speech problems related to VPD appeared to be similar among the different groups (CFM without CL/P, CFM with CL/P, CL/P without CFM). As 15.2% of all CFM patients and 8.5% of CFM patients without CL/P had VPD, it is proposed that all patients with CFM, with or without CL/P, should be assessed by a speech and language therapist for the potential risk of VPD., Competing Interests: Competing interests None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate condylar bone density (BD) in children with craniofacial microsomia (CFM) and identify factors that contribute to early stage condylar resorption (CR) after mandibular distraction osteogenesis (MDO)., Design: Retrospective study., Setting: Craniofacial department of a plastic surgery hospital., Patients: Fifty-one children with CFM classified as Pruzansky IIa based on complete pre-(T0) and post-MDO (T1) computed tomography (CT) data., Intervention and Main Outcome Measurements: Mimic 21.0 (Materialise Inc., Belgium) was used to measure bilateral BD and condylar height (CH) and volume (CV) of affected side. Children were split into groups based on either affected side BD or the distraction length (DL,25 mm as cutoff) .Bilateral BD was compared using a paired t-test in each group. The CH and CV of affected side at T0 and T1 were compared. The relative values of the CH and CV (CH ratio) and the volume (CV ratio) of the affected side were compared across the groups., Results: The BD was lower on affected side than on unaffected side. Regarding BD, CH and CV decreased after MDO in group I, while the CH ratio and CV ratio of group I was lower than that of groups II and III. Regarding DL, the CV ratio was lower in Group L than Group S., Conclusions: The condylar bone quality on affected side is compromised in type IIa CFM. A low BD in combination with a larger distraction distance may increase the risk of CR; therefore, MDO in patients with such characteristics should be postponed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Craniofacial microsomia (CFM) primarily includes specific head and neck anomalies that co-occur more frequently than expected. The anomalies are usually asymmetric and affect craniofacial features; however, there are frequently additional anomalies of variable severity. Published prenatal findings for CFM are limited. This study contributes 11 cases with CFM and their anomalies identified prenatally. Cases born between January 1, 1997 and December 31, 2019 with CFM were abstracted from the Alberta Congenital Anomalies Surveillance System, which is a population-based program ascertaining congenital anomalies for livebirths, stillbirths, and termination of pregnancies for fetal anomalies. There were 11 cases ascertained with prenatal findings including facial anomalies: one each with left cleft lip, right microtia, and bilateral microphthalmia. Two cases had vertebral anomalies. In addition, anomalies of the kidneys, brain, heart, and radial ray were identified. Six (55%) had a single umbilical artery, five (45%) were small for gestational age, and three (27%) were from a twin pregnancy that were discordant for anomalies. Four (36%) overlapped another proposed recurrent constellations of embryonic malformation condition. This study describes prenatal findings for 11 cases with CFM. Comparable to prior published cases, there were recurring anomalies on prenatal imaging, including anomalies of the brain, eye, heart, kidneys, and radial ray, which may aid in the prenatal diagnosis of CFM., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Objective: The aim of this study was to evaluate the volumetric airway changes using three-dimensional images following unilateral vertical mandibular distraction osteogenesis (uVMD) among patients with hemifacial microsomia (HFM)., Design: This retrospective study analyzed cone-beam computed tomography (CBCT) scans of patients with HFM at three different timepoints; pretreatment (T0), posttreatment (T1), and at least 6 months post-distraction (T2). The individuals underwent uVMD between December 2018-Januaray 2021. The nasopharyngeal (NP) volume, oropharyngeal (OP) volume, and the area of maximum constriction (MC) were measured. Wilcoxon signed-rank test was used to compare the airway volumes between T0-T1, T1-T2, and T0-T2., Results: Five patients met the inclusion criteria (mean age = 10.4 years; 1 female, 4 males). Intraclass correlation analysis showed excellent interrater reliability ( r  > .86, P  < .001). Posttreatment, the OP airway volume exhibited a significant mean increase of 56% ( P  = .043) from T0 to T1, but decreased from T1-T2 by 13%. Likewise, the total airway volume presented with a significant mean increase of 48% between T0-T1 ( P  = .044), and a decrease of 7% from T1-T2. The changes in the NP airway volume and area of MC were not statistically significant ( P   >   .05 ), but an increase in the mean values were observed., Conclusion: Surgical intervention with uVMD may significantly increase the OP airway volume and the total airway volume among patients with HFM immediately after distraction. However, the statistical significance diminished after six months post-consolidation, but the mean percent change may remain of clinical significance. The NP volume did not seem to show significant changes in response to uVMD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The study aimed to summarize current knowledge regarding the use of orthopaedic functional appliances (OFA) in managing unilateral craniofacial microsomia (UCM). The eligibility criteria for the review were (1) assessing use of OFA as a stand-alone treatment and (2) using OFA in combination during or after MDO. The PICO (population, intervention, comparison and outcome) format formulated clinical questions with defined inclusion and exclusion criteria. No limitations concerning language and publication year were applied. Information sources: A literature search of Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, Web of Science databases without restrictions up to 30 September 2022. The risk of bias was assessed. According to Cochrane and PRISMA guidelines, two independent authors conducted data extraction. The level of evidence for included articles was evaluated based on the Oxford evidence-based medicine database. Due to the heterogeneity of studies and insufficient data for statistical pooling, meta-analysis was not feasible. Therefore, the results were synthesized narratively. A total of 437 articles were retrieved. Of these, nine met inclusion criteria: five assessing OFA and four assessing OFA during or after MDO. There is limited evidence to suggest that stand-alone and combination treatment with OFA is beneficial for treating mild-to-moderate UCM-related dentofacial deformities in short term. No studies assessed the burden of care. In the management of UCM, there is insufficient evidence supporting the efficacy of OFA as a stand-alone treatment or when combined with MDO. Additionally, there is a lack of evidence regarding treatment protocols and the effect on the condyles and the TMJ. The study was registered at Prospero database number CRD42020204969., (© 2023 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27 . cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27 -/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Objective: Determine if the ideal location of the construct in microtia reconstruction for hemifacial microsomia (HFM) can be more accurately derived from measurements on the cranium., Design: High-resolution computerized tomography (CT) images were analyzed through craniometric linear relationships., Setting: Our tertiary care institution from 2000 to 2021., Patients/participants: Patients diagnosed with HFM and microtia, who had high-resolution craniofacial CT scans, yielding 36 patients accounting for 44 CT scans., Main Outcome Measure(s): First, the integrity of the posterior cranial vault among HFM patients was determined. If proven to be unaffected, it could be used as a reference in the placement of the construct. Second, the position of the ear in relation to the cranium was assessed in healthy age-matched controls. Third, if proven to be useful, the concordance of these cranium-based relationships could be validated among our HFM cohort., Results: The posterior cranial vault is unaffected in HFM ( P > .001). Further, craniometric relationships between the tragus and the Foramen Magnum, as well as between the tragus and the posterior cranium, have been shown to be highly similar and equally precise in predicting tragus position in healthy controls ( P > .001). These relationships held true across all age groups ( P > .001), and importantly among HFM patients, where the mean absolute difference in predicted tragus position never surpassed 1.5 mm., Conclusions: Relationships between the tragus and the cranium may be used as an alternative to distorted facial anatomy or surgeon's experience to assist in pre-operative planning of construct placement in microtia reconstruction for HFM patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The aim of this study is to present a sequential strategy of soft-tissue, non-osteogenic distraction with a novel device, followed by microvascular bony reconstruction for severe cases of mandibular hypoplasia. The case of a 21-year-old woman with Goldenhar syndrome is presented, whose mandible remained severely hypoplastic despite previous attempts at distraction and was not suitable for further osteogenic distraction. Soft tissue deficiency and pin track scarring prevented free fibular transfers. A personalized distractor, anchored to the cranium and the mandibular symphysis, was designed to expand the soft tissues while allowing for physiological temporomandibular joint (TMJ) movement without compression forces. Internal distractors were placed along the osteotomies to prevent condylar luxation. After completion of the soft tissue distraction, the native mandible was resected except for the condyles and reconstructed with two free fibula flaps. This report represents the proof of concept of a sequential approach to severe lower face soft-tissue and bone deficiency, which preserves TMJ function and avoids the transfer of poorly matched skin to the face., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To characterise the morphology of temporal bone in patients with craniofacial microsomia (CFM)., Design: A retrospective study., Setting: A craniofacial centre., Patients: Ninety-four patients with unilateral craniofacial microsomia., Interventions: Mimics 21.0 (Materialise Inc., Belgium) was used to locate temporal bone landmarks on preoperative computed tomography data. The spatial Cartesian coordinate system was established in 3-matic 13.0 (Materialise Inc., Belgium). The coordinates of each landmark and the distances and angles between the landmarks were calculated. A classification system was used to quantify the severity of the zygomatic arch deformity., Main Outcome Measure(s): The bilateral differences in coordinates, linear and angular measurements, and the severity of temporal bone deformity (TTL δ, Psag δ, Paxiδ, and Tsag δ) among the groups were compared using the paired t-test and Kruskal-Wallis test, respectively., Results: Compared to those of the unaffected side, the landmarks of the inner ear and petrous part on the affected side showed a decrease in the Z-coordinate or an increase in the X-coordinate. A superolateral rotation tendency of the temporal bone on the affected side was found. There were no significant differences in the linear and angular measurements between the groups. The degree of zygomatic arch deformation was lower in the mild group; however, no significant difference was found between the moderate and severe groups., Conclusions: In patients with CFM, asymmetry of the temporal bone and its inner organs (vestibulocochlear organ, facial nerve, and vessels) exists in multiple dimensions; its severity is not completely consistent with the degree of mandibular involvement.

Objective: The aim of this study was to evaluate the outcomes of orthognathic surgery (OGS) in patients with craniofacial microsomia (CFM) who had previously undergone mandibular distraction osteogenesis (MDO)., Design: A retrospective cohort study was performed including all patients with CFM who were treated with OGS at a single institution between 1996 and 2019. The clinical records, operative reports, and cone beam computed tomography (CBCT) scans were reviewed. CBCT data before OGS (T1), immediately after OGS (T2), and at long-term follow-up (T3) were analyzed using Dolphin three-dimensional software to measure the occlusal cant and chin point deviation., Results: The study included 12 patients with CFM who underwent OGS (6 underwent OGS without MDO and 6 underwent OGS after MDO). There was a statistically significant improvement in occlusal cant and chin point deviation in both groups postoperatively. Occlusal cant relapsed by a mean of 0.6° (standard deviation [SD] 1.1°) in the patients who had OGS alone compared with 0.7° (SD 1.2°) in the patients who had OGS after MDO ( P   =  .745) between T2 and T3. There was no statistically significant difference in chin point relapse between patients who had OGS alone compared with those who had OGS after MDO (0.1 mm [SD 2.5mm] vs 0.7mm [SD 2.2mm]; P   =  .808)., Conclusions: Within the limitations of this study, these findings suggest that OGS after MDO in patients with CFM can produce stable results., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To report a case of a 4-year-old patient with Goldenhar syndrome., Case Presentation: The author presents a rare case report involving a 4-year-old boy with multiple malformations. A comprehensive examination showed that the patient primarily had a limbal dermoid. He also has bilateral microtia and ear canal deformities. The skull CT scan and spine X-ray showed Maxillofacial Abnormalities and scoliosis. Whole Exome Sequencing revealed potential gene variations related to microtia. Although certain circumstances prevented us from initiating follow-up treatment for the patient, we have provided a detailed account of the diagnostic methodologies used for this condition., Conclusions: Goldenhar syndrome is a congenital condition, predominantly presenting as sporadic cases. Its diagnosis and management typically necessitate the involvement of multiple disciplines, including otolaryngology and craniofacial surgery. The syndrome encompasses a variety of craniofacial features, which can facilitate early diagnosis and guide subsequent therapeutic interventions., (© 2024. The Author(s).)

Hypoplastic asymmetry due to hemifacial microsomia (HFM) often represents the most difficult reconstruction in the craniomaxillofacial clinic. Although autogenous grafts are generally used for temporomandibular joint reconstruction (TMJR), the use of TMJR prostheses is not well established. The aim of this review was to identify, collect and analyse the use of extended TMJR (eTMJR) prostheses in patients with HFM, describing clinical features, surgical procedures and postoperative complications. Online searches of all major databases were performed according to PRISMA guidelines. All studies with HFM patients treated with the eTMJR prostheses were included. Descriptive statistics were used for data analysis. A total of 19 studies, including 08 case studies, 06 case series and 05 retrospective cohort studies, met the inclusion criteria, where a total of 42 HFM patients were reported from 18 countries, mostly from the United States (05; 26%). Fifteen of the 42 cases (~36%) were male. The mean ± SD (range) age of patients in all studies was 19.79 ± 5.81 (9-36) years. The mean ± SD (range) of patient follow-up was 41.30 ± 35.50 (6-136) months. A total of 5 (10.6%) patients were implanted with bilateral eTMJR prostheses. The Pruzansky classification was used in 18 (~89.5%) studies, OMENS classification in 01 (~5%) study, whereas no classification was reported in one study. Only 01 (7.1%) study had documented the eTMJR classification for the prosthesis used. In growing patients with or without a history of failed autogenous tissues, TMJR prostheses may provide a viable alternative. Randomized studies with large cohorts are warranted to validate these preliminary results., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The study analyzed vascular variations in microtia associated with hemifacial microsomia (HFM). A retrospective analysis was conducted on 47 patients with microtia and HFM, who underwent computed tomography angiography between November 2011 and May 2022. The vascular course and branching supplying the TPF were analyzed. Craniometric measurements were conducted to determine the horizontal distance from the porion and fronto-zygomatic suture (F-Z suture) to the vessels. On the affected side, the TPF was primarily supplied by either the superficial temporal artery (STA) or the postauricular artery-originated STA (Po-STA). The Po-STA (n = 29) was more prevalent than the STA (n = 18), and mostly exhibited a single frontal branch (n = 20). Craniometric analysis revealed that the Po-STA was closer to the porion, ear vestige, and F-Z suture than the STA on the non-affected side. Furthermore, a significant correlation was observed between the severity of mandibular hypoplasia and presence of Po-STA variation (Cramer's V = 0.498, p = 0.005). Microtia associated with HFM exhibits vascular variations in the TPF - in particular, a unique Po-STA variation. The Po-STA is prone to injury during ear reconstruction because of its proximity to the external auditory canal and ear vestige. Surgeons should be cautious of these anatomical variations for safer ear reconstruction procedures, and utilize preoperative imaging for meticulous planning., Competing Interests: Declaration of competing interest The authors have no commercial associations to declare., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Hemifacial microsomia (HFM) is a common birth defect involving the first and second branchial arch derivatives. Although several chromosomal abnormalities and causal gene variants have been identified, genetic etiologies in a majority of cases with HFM remain unknown. This study aimed to identify genetic mutations in affected individuals with HFM., Methods: Whole-exome sequencing and bioinformatics analysis were performed for 16 affected individuals and their family members. Sanger sequencing was applied for confirmation of selected mutations. Zebrafish embryos were used for in situ hybridization of candidate gene, microinjection with antisense morpholino, and cartilage staining., Results: A homozygous missense mutation (c.484G > A; p.V162I) in the FRK gene was identified in an 18-year-old girl with HFM and dental abnormalities. Heterozygous mutation of this mutation was identified in her parents, who are first cousins in a consanguineous family. FRK is highly expressed in the Meckel's cartilage during embryonic development in mouse and zebrafish. Knockdown of frk in zebrafish showed a lower length and width ratio of Meckel's cartilage, abnormal mandibular jaw joint, and disorganized ceratobranchial cartilage and bone., Conclusions: We identified a recessive variant in the FRK gene as a novel candidate gene for a patient with HFM and mandibular hypoplasia and revealed its effects on craniofacial and embryonic development in zebrafish., (© 2022 Wiley Periodicals LLC.)

Objective: To preliminarily verify the effectiveness of self-designed artificial condyle-mandibular distraction (AC-MD) complex in the treatment of Pruzansky type ⅡB and Ⅲ hemifacial microsomia (HFM) through model test., Methods: Five children with Pruzansky type ⅡB and Ⅲ HFM who were treated with mandibular distraction osteogenesis (MDO) between December 2016 and December 2021 were selected as the subjects. There were 3 boys and 2 girls wih an average age of 8.4 years (range, 6-10 years). Virtual surgery and model test of AC-MD complex were performed according to preoperative skull CT of children. The model was obtained by three-dimensional (3D) printing according to the children's CT data at a ratio of 1∶1. The occlusal guide plate was designed and 3D printed according to the children's toothpaste model. The results of the model test and the virtual surgery were matched in three dimensions to calculate the error of the residual condyle on the affected side, and the model test was matched with the actual skull CT after MDO to measure and compare the inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible., Results: The error of residual condyle was (1.07±0.78) mm. The inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible after 3D printing model test were significantly larger than those after MDO ( P <0.05)., Conclusion: In the model test, the implantation of AC-MD complex can immediately rotate the mandible to the horizontal position and improve facial symmetry, and the residual condyle segment can be guided close to the articular fossa or the preset pseudoarticular position of the skull base after operation.

Objective: To report associated congenital anomalies with unexplained craniofacial microsomia (CFM) and the phenotypic overlap with other recurrent constellations of embryonic malformations (RCEM), and to assess prenatal and perinatal risk factors., Study Design: This is a retrospective cross-sectional study. Cases with CFM, delivered between January 1, 1997, and December 31, 2019, were abstracted from the population-based Alberta Congenital Anomalies Surveillance System. Livebirths, stillbirths, and early fetal losses were reviewed to include all types of pregnancy outcomes along the spectrum of this condition. Prenatal and perinatal risk factors were compared with the Alberta birth population to assess differences between the 2 groups., Results: There were 63 cases with CFM, yielding a frequency of 1 per 16 949. There was a high rate of cases (65%) with anomalies outside the craniofacial and vertebral regions. Congenital heart defects were the most common (33.3%). A single umbilical artery was found in 12.7% of cases. The twin/triplet rate of 12.7% was significantly higher than the Alberta rate of 3.3% (P < .0001). There was an overlap with a second RCEM condition in 9.5% of cases., Conclusions: Although CFM is primarily a craniofacial condition, the majority of cases have congenital anomalies affecting other systems requiring additional assessments, including an echocardiogram, renal ultrasound examination, and a complete vertebral radiograph. The high rate of an associated single umbilical artery raises the possibility of a related etiological mechanism. Our findings support the proposed concept of RCEM conditions., Competing Interests: Declaration of Competing Interest No additional funding source was required for this study. The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis., (© 2023 Wiley Periodicals LLC.)

Hemifacial microsomia (HFM), one of the most common congenital facial anomalies, was usually treated with the bilateral sagittal split osteotomy (BSSO) procedure to correct the asymmetric appearance and malocclusion of the mandible. However, the frequent post-operative relapse incidents would lead to the restoration of the mandibular segment to its preoperative position and failure of the BSSO procedure. In this study, a customized asymmetric fixed plate (CAF plate) was developed to resist relapse due to hemifacial microsomia occlusal forces and the different muscular traction forces on both sides of the mandible. For the actual HFM case in this study, the reconstructed mandibular segmental bone model was fixed using BSSO with a rectangular plate (the original CAF plate appearance) in the topology optimization analysis. With the topology optimization technique, the CAF plate was designed with a lightweight profile and excellent structural strength in consideration of the HFM asymmetrical muscle traction and occlusal force. Using biomechanical simulations, the von-Mises stress and CAF plate mandibular segment displacement and the miniplate were compared to evaluate which had superior relapse resistance. In the in-vitro biomechanical test, a fatigue force of 250,000 cycles and a constant muscle traction force were applied to the HFM mandibular model, which was fixed with the CAF plate fabricated using metal 3D printing (selective laser melting, SLM) to obtain the mandibular segment displacement as a relapse assessment. The topology optimization analysis showed that the CAF plate has the best characteristics, light weight and structural strength with 30% volume retention. The biomechanical analysis showed that the maximum von Mises stress of the mini-plate was 2.71 times higher than that of the CAF plate. The relapse displacement of the mandibular segment fixed with the mini-plate was 1.62 times higher than that fixed with the CAF plate. The CAF plate ability to resist relapse was confirmed by the biomechanical testing results so that only 0.29 mm of recurrence displacement was observed in the mandibular segment. The results indicated that the CAF plate structural strength and resistance to relapse was significantly better than that of the mini-plate. This study developed a customized asymmetric fixation plate for hemifacial microsomia, integrating topology optimization, metal 3D printing, and in vitro biomechanical testing to resist occlusal forces and differential muscle traction on both sides of the mandible to reduce relapse and improve fixation stability., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective: To investigate the effectiveness of autologous nano-fat mixed granule fat transplantation in the treatment of facial soft tissue dysplasia in children with mild hemifacial microsomia (HFM)., Methods: A total of 24 children with Pruzansky-Kaban type Ⅰ HFM were admitted between July 2016 and December 2020. Among them, 12 children were treated with autologous nano-fat mixed granule fat (1∶1) transplantation as study group and 12 with autologous granule fat transplantation as control group. There was no significant difference in gender, age, and affected side between groups ( P >0.05). The child's face was divided into region Ⅰ(mental point-mandibular angle-oral angle), region Ⅱ (mandibular angle-earlobe-lateral border of the nasal alar-oral angle), region Ⅲ (earlobe-lateral border of the nasal alar-inner canthus-foot of ear wheel). Based on the preoperative maxillofacial CT scan+three-dimensional reconstruction data, the differences of soft tissue volume between the healthy and affected sides in the 3 regions were calculated by Mimics software to determine the amount of autologous fat extraction or grafting. The distances between mandibular angle and oral angle (mandibular angle-oral angle), between mandibular angle and outer canthus (mandibular angle-outer canthus), and between earlobe and lateral border of the nasal alar (earlobe-lateral border of the nasal alar), and the soft tissue volumes in regions Ⅰ, Ⅱ, and Ⅲ of healthy and affected sides were measured at 1 day before operation and 1 year after operation. The differences between healthy and affected sides of the above indicators were calculated as the evaluation indexes for statistical analysis. At 1 year after operation, the parents, the surgeons, and the nurses in the operation group made a self-assessment of satisfaction according to the frontal photos of the children before and after operation., Results: The study group and the control group were injected with (28.61±8.59) and (29.33±8.08) mL of fat respectively, with no significant difference ( t =0.204, P =0.840). After injection, 1 child in the control group had a little subcutaneous induration, and no related complications occurred in the others. All children in both groups were followed up 1 year to 1 year and 6 months, with an average of 1 year and 4 months in the study group and 1 year and 3 months in the control group. At 1 year after operation, the asymmetry of the healthy and affected sides improved in both groups; the satisfactions of parents, surgeons, and nurses in the study group were all 100% (12/12), while those of the control group were 100% (12/12), 83% (10/12), and 92% (11/12), respectively. The differences between healthy and affected sides in mandibular angle-oral angle, mandibular angle-outer canthus, earlobe-lateral border of the nasal alar, and the soft tissue volume in 3 regions of the two groups after operation were significantly smaller than those before operation ( P <0.05). There was no significant difference in the above indexes between the two groups before operation ( P >0.05). After operation, all indexes were significantly lower in study group than in control group ( P <0.05)., Conclusion: Autologous nano-fat mixed granule fat transplantation and autologous granule fat transplantation can both improve the facial soft tissue dysplasia in children with mild HFM, and the former is better than the latter.

This study aimed to investigate the potential progressiveness of mandibular asymmetry and to study factors that influence chin point deviation in patients with unilateral craniofacial microsomia (CFM). Paediatric patients with unilateral CFM with available radiologic imaging and medical photographs were included. Chin point deviation was measured on clinical photographs. A Jonckheere-Terpstra test and linear mixed model for repeated measurements assessed the relation of chin point deviation on natural growth, Pruzansky-Kaban score, and soft tissue score. A total of 110 patients were included. The linear mixed model showed no statistically significant changes of chin point deviation during growth (effect estimate -0.006°, 95% CI -0.04° to -0.03°, p = 0.74). A statistical significant relation between both the Pruzansky-Kaban and soft tissue score on chin point deviation was found (effect estimate -5.10°, 95% CI -6.45° to -3.75°, p ≤ 0.001 and effect estimate -3.42°, CI -5.86° to -0.98°, p ≤ 0.001, respectively). Within the limitations of the study it seems that craniofacial microsomia may be a non-progressive disorder, because chin point deviation did not change over time., Competing Interests: Declaration of competing interest There are no conflicts of interest in the materials or subject matter dealt with in the manuscript., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hemifacial microsomia (HFM) is a congenital craniofacial malformation, and its features include hypoplasia and asymmetry in skeletal tissue and soft tissue. These features are usually associated with a difficult airway. Mandibular distraction osteogenesis can achieve mandibular advancement, but its effect on the subsequent laryngoscopic views has not been adequately documented., Aim: The aim of this study was to determine the change in laryngoscopic views after mandibular distraction osteogenesis (MDO) in children with HFM and to examine the radiological changes after MDO by using computed tomography (CT)-based three-dimensional (3-D) airway reconstruction., Methods: An observational prospective study was carried out in children with HFM undergoing MDO. All children underwent 3-D airway reconstruction preoperatively before the placement and removal of the distractor. The temporomandibular joint lesions in children were classified by the Pruzansky-Kaban classification. The Cormack-Lehane grade was assessed after induction under direct laryngoscopy. The relationship between difficult laryngoscopy and the Pruzansky-Kaban classification was assessed. Changes in the upper pharyngeal airway parameters and laryngoscopic views were analyzed., Results: Forty children (ages ranging from 5 to 16 years, males = 26, females = 14) with HFM underwent 80 anesthesia for MDO. The incidence of difficult laryngoscopy before mandibular distraction was 5/12 (41.7%) in type IIa, 19/24 (79.2%) in type IIb and 1/4 (25%) in type III HFM. The mean difference in the incidence of difficult laryngoscopy before and after MDO was 33.3% (95% CI: -6.7% to 73.3%), 50.0% (95% CI: 8.4% to 91.6%), and 0% for type IIa, type IIb, and type III, respectively. In type IIb, 12/19 cases of difficult laryngoscopy became easy after mandibular distraction: this was associated with an increase in the palatopharyngeal and glossopharyngeal CT parameters (p < .05). In type IIa, 5/5 cases of difficult laryngoscopy became easy after mandibular distraction, and 1/7 cases of easy laryngoscopy became difficult laryngoscopy. However, there were no significant changes in the palatopharyngeal, glossopharyngeal, and hypopharyngeal CT parameters in type IIa and type III HFM (p > .05)., Conclusions: MDO can improve the laryngoscopic views in children with HFM. According to the Pruzansky-Kaban classification, children with type IIb showed the highest incidence of difficult laryngoscopy before MDO. After MDO, the improvement in laryngoscopic views under direct laryngoscopy in type IIb was related to the increase in the palatopharyngeal and glossopharyngeal volume., (© 2022 Acta Anaesthesiologica Scandinavica Foundation.)

Background: Owing to the complex clinical manifestations of hemifacial microsomia (HFM), multidisciplinary cooperation is required to achieve better therapeutic effects in terms of function and aesthetics. This study aimed to explore the efficacy of the expanded two-flap auricular reconstruction combined with mandibular distraction osteogenesis in the treatment of HFM., Methods: This surgical strategy was performed in three stages. In the first stage, the retroauricular skin was expanded with a tissue expander and a mandibular distraction device was installed. In the second stage, the traditional expanded two-flap method for auricular reconstruction was adapted, and the framework was fabricated with costal cartilage and wrapped with the expanded skin flap, retroauricular fascia flap, and full-thickness skin graft. In the final stage, the tragus and lobule were rebuilt, the concha cavity deepened, and the mandibular distraction device removed., Results: From January 2014 to November 2018, 166 HFM patients underwent auricular reconstruction with the expanded two-flap method and simultaneous mandibular extension in our hospital. The median follow-up period was 9.3 months. Of the 166 patients, 154 patients and their families were satisfied with the results, and only 16 patients experienced complications., Conclusions: This three-stage technique of simultaneous auricular reconstruction and mandibular distraction osteogenesis is safe and effective in achieving facial symmetry, improving occlusal contact, shortening treatment course, and relieving patient's suffering, especially for HFM patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aim: This article provides a review of a decade of clinical research studies on clinical features, medical interventions, and surgical interventions for individuals with craniofacial microsomia (CFM). We also provide recommendations for future clinical research., Method: A systematic search of literature was conducted in Embase and PubMed/MEDLINE Ovid. All publications from 2010 to 2020 that included at least 10 individuals with CFM were considered relevant for this study., Results: A total of 91 articles were included. In the past decade, many new studies on CFM have been published providing more insight on the diagnosis and management of patients with CFM. This review encompasses findings on the clinical difficulties patients with CFM encounter, including the craniofacial and extracraniofacial characteristics of patients with CFM and its related clinical consequences on breathing, feeding, speech, and hearing., Conclusions: A considerable number of large multicenter studies have been published in recent years, providing new insights in the clinical consequences of CFM. The phenotypic variety between patients with CFM makes patient-specific treatment tailored to individual needs essential. The research and development of clinical care standards might be challenging because of the heterogeneity of CFM. Future research on clinical and patient-reported outcomes can help identify optimal treatment strategies. Cooperation between craniofacial centers, using uniform registration and outcome measurement tools, could enhance research and future care for these patients., Level of Evidence: Level IV., Competing Interests: Declaration of Competing Interest There are no conflicts of interest in the materials or subject matter dealt with in the manuscript., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.)

The treatment management of patients with hemifacial microsomia (HM) includes both surgical and nonsurgical approaches and depends primarily on the degree of deformity of the facial and skeletal structures. In this context, the combined efforts of the maxillofacial surgeon, the orthodontist, and the prosthodontist are essential for a satisfactory functional and esthetic outcome. Case presentation: A 31-year-old man presented with a chief complaint of facial asymmetry. The patient had been diagnosed with HM on the right side, with severe external ear deformity, and hypoplasia of the facial muscles and the zygomatic bone. The intraoral examination showed a Class I molar and canine relationship with a reduced horizontal overlap and an occlusal plane canting. The maxillary anterior teeth were severely worn due to traumatic occlusion. Orthodontic treatment in conjunction with combined orthognathic surgery was planned to address the facial asymmetry. Ramus distraction osteogenesis was carried out, followed by conventional presurgical orthodontic treatment. The treatment was completed by prosthetic rehabilitation for the reconstruction of the maxillary teeth and fine occlusal adjustment. Conclusion: The cooperation between the orthodontist, surgeon, and prosthodontist becomes indispensable when treating complex cases of HM. An interdisciplinary approach should be adopted from the start of treatment, promoting integrated customized care.

In this study, the aim was to assess whether using elastic traction during the active period of distraction osteogenesis could effectively increase the vertical extension. Patients with Pruzansky-Kaban Type II mandibular deformity were recruited and randomly assigned into Elastic traction + Distraction Osteogenesis group or Distraction Osteogenesis group, respectively. During the active period, the experimental group received orthodontic elastic traction 3 days after distraction osteogenesis implantation, while the control group received no treatment. All the participants underwent computed tomography (CT) examination before surgery, at the end of the active period, 6 months and 2 years after distraction osteogenesis tractor implantation. The primary outcome was the effective vertical extension rate of the mandible from the baseline to the end of the active period after operations, and there were 7 secondary outcomes used. 70 patients were included. The effective vertical extension rates were 85.021% ± 7.432% (mean ± SD) and 68.811% ± 9.510% (mean ± SD) in the experimental and control groups, respectively (P = 0.001). The average distances between the lower middle incisor point to the sagittal plane at the end of the active period were 2.485 ± 1.411 mm and 3.938 ± 2.293 mm in the experimental and control groups, respectively (P = 0.026). At the end of the active period of distraction osteogenesis, the average values of the mandibular occlusal plane canting were -4.887 ± 3.126 mm and -0.177 ± 4.029 mm in the experimental and control groups, respectively (P = 0.026). Elastic traction-assisted distraction osteogenesis could improve traction efficiency and facial symmetry., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The aim of this multicentre retrospective cohort study was to describe and categorize the types of ocular and adnexal anomalies seen in patients with craniofacial microsomia (CFM) and to determine their prevalence. In addition, the relationship between the OMENS-Plus and Pruzansky-Kaban classification for each patient and the presence of ocular anomalies was investigated. A total of 881 patients with CFM from four different craniofacial centres were included. Data on ocular anomalies were gathered from the patient charts. Ocular anomalies were present in 33.9% of patients. Four subgroups of ocular and adnexal anomalies were identified. Type I ocular anomalies were present in 22.2%, type II in 19.0%, type III in 18.4%, and type IV in 14.5%. Several potentially preventable and treatable ocular anomalies were identified. Higher OMENS-Plus classification orbit and soft tissue scores and Pruzansky-Kaban classification mandible scores were associated with an increased risk of ocular anomalies. Based on these results and the clinical implications ocular anomalies may have, we underline the importance of targeted ophthalmological screening in CFM. Healthcare professionals should be aware of the possibility of ocular anomalies in these patients, especially during the critical period for visual development., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Overview: The authors successfully treat a case of hemifacial microsomia involving unilateral condylar hypoplasia using conventional orthodontic techniques followed by long-term retention., Case Description: A girl aged 10 years and 2 months received a diagnosis of hemifacial microsomia resulting from unilateral condylar hypoplasia. During a growth period, premature incisal contact was abolished. After her growth was complete, she received conventional orthodontic treatment with preadjusted edgewise appliances. After 27 months of multibracket treatment, acceptable occlusion with a class I canine and molar relationship was achieved. The occlusion remained stable throughout the 15-year retention period, although there was a slight facial change., Conclusions and Practical Implications: Early orthodontic management only can have some limitations but could be one of the treatment options for hemifacial microsomia., (Copyright © 2021 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Current research about hemifacial microsomia (HFM) patients after distraction osteogenesis (DO) most emphasize the morphologic changes. This case report shows the outcome of DO on the upper airway of a HFM patient with obstructive sleep apnea (OSA) based on the use of computational fluid dynamics (CFD)., Case Presentation: An 11-year-old boy was diagnosed as HFM with OSA, and underwent unilateral DO. Polysomnography and CT scans were performed before and 6 months after treatment. After DO, lowest blood oxygen saturation increased from 81% to 95% and apnea and hypopnea index decreased from 6.4 events/hour to 1.2 events/hour. The oropharynx and nasopharynx were obviously expanded. We observed apparently increased average pressure, decreased average velocity and pressure drop in all cross-sections, and largely decreased airflow resistance and maximum velocity entirely in the airway., Conclusions: The results suggest that DO might be effective for the treatment of OSA by expanding the upper airway and reducing the resistance of inspiration., (© 2021. The Author(s).)

Phenotypic severity dictates the timing and type of surgical intervention required. Mandibular distraction in children without respiratory and feeding difficulties remains controversial with regard to long-term mandibular growth outcomes and reducing surgical burden. Early mandibular distraction does not obviate secondary orthognathic surgery at skeletal maturity; it provides improved functional, aesthetic, and psychosocial outcomes, at least in the short term. Costochondral rib grafting for Pruzansky type IIB and III mandibles can produce reliable results, especially when combined with subsequent mandibular distraction. Secondary 2-jaw orthognathic surgery plus genioplasty at skeletal maturity benefits from improved bone volume from prior mandibular distraction., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anatomic studies have identified that patients with Treacher Collins syndrome and some cases of bilateral craniofacial microsomia are characterized by multilevel airway obstruction as a result of hypoplasia and clockwise rotation of the maxillomandibular complex. Patients often remain tracheostomy-dependent despite multiple airway surgeries. Counterclockwise craniofacial distraction osteogenesis aims to correct the facial skeletal deformity and expand the upper airway volume by rotating the subcranial complex en bloc around the nasofrontal junction. Early results have demonstrated significant increases in the nasopharyngeal and oropharyngeal airway volumes with successful decannulation in a majority of patients who have undergone this operation., Competing Interests: Disclosure Dr R.A. Hopper is the inventor on a patent licensed to KLS Martin LP. No other financial interest to disclose., (Published by Elsevier Inc.)

Objective: The study aim was to assess behavioral adjustment in preschool children with and without craniofacial microsomia (CFM)., Design: Multisite cohort study of preschoolers with CFM ("cases") or without CFM ("controls")., Participants: Mothers (89%), fathers (9%), and other caregivers (2%) of 161 preschoolers., Outcome Measure: Child Behavior Check List (CBCL 1.5-5); linear regressions with standardized effect sizes (ES) adjusted for sociodemographic confounds., Results: Child Behavior Check Lists for 89 cases and 72 controls (average age 38.3 ± 1.9 months). Children were male (54%), white (69%), and of Latino ethnicity (47%). Cases had microtia with mandibular hypoplasia (52%), microtia only (30%), or other CFM-associated features (18%). Nearly 20% of cases had extracranial anomalies. Composite CBCL scores were in the average range compared to test norms and similar for cases and controls. On the subscales, cases' parents reported higher Anxious/Depressed scores (ES = 0.35, P = .04), Stress Problems (ES = 0.40, P = .04), Anxiety Problems (ES = 0.34, P = .04), and Autism Spectrum Problems (ES = 0.41, P = .02); however, the autism subscale primarily reflected speech concerns. Among cases, more problems were reported for children with extracranial anomalies and certain phenotypic categories with small ES., Conclusions: Behavioral adjustment of preschoolers with CFM was comparable to peers. However, parental reports reflected greater concern for internalizing behaviors; thus, anxiety screening and interventions may benefit children with CFM. Among cases, more problems were reported for those with more complex presentations of CFM. Craniofacial microsomia-related speech problems should be distinguished from associated psychosocial symptoms during developmental evaluations.

Objectives: This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky-Kaban classification system., Materials and Methods: Cone-beam computed tomography images of 48 adult CFM cases were collected. The asymmetry of the mandibular body and ramus was analyzed with 3D landmarks. The mirrored mandibular model was registered on the original model, yielding a color-coded distance map and an average distance (i.e., asymmetry score) to quantify the overall mandibular asymmetry., Results: The lengths of the mandibular body and ramus were significantly shorter on the affected than the contralateral side (p < 0.001). The ANB (p = 0.009), body and ramal lengths (both p < 0.001), and body and ramal length asymmetry (both p < 0.05) were significantly different between mild (types I/IIA) and severe (types IIB/III) cases. The mandibular asymmetry score correlated with mandibular body length asymmetry (r = 0.296, p = 0.046). CFM mandibles showed high variability in shape asymmetry., Conclusions: CFM patients showed distinct body and ramal length asymmetries. In severe cases, mandibles were smaller, more retruded, and more asymmetric in length. The mandibular shape asymmetry was highly variable regardless of the Pruzansky-Kaban types, being a determinant in the extent of overall mandibular asymmetry., Clinical Relevance: The 3D morphologic analysis provides better insights into real mandibular asymmetry. Although the Pruzansky-Kaban classification was applied, high individual variability of the mandibular morphology still existed within the types. Therefore, individualized analyses and treatment plans for CFM patients are highly recommended.

Objective: An increasing number of patients use social media for health-related information and social support. This study's objective was to describe the content posted on Facebook groups for individuals with microtia and/or craniofacial microsomia (CFM) and their families in order for providers to gain insight into patient and family needs and experiences to inform clinical care., Methods: Two months of posts, images, comments, and "like" responses from two Facebook groups in the US and the UK were recorded and analyzed using content analysis. A secondary analysis identified statements of emotion., Results: Posts (N = 254) had a total of 7912 "like" responses, 2245 comments, and 153 images. There were three categories of posts: seeking guidance (43%; 9 themes), promoting events/news (33%; 5 themes), and sharing experiences (24%; 3 themes). Across categories, 16% of posts had emotional content. Most comments were responding to posts seeking guidance, including medical care (20%), surgical care (9%), and hearing aids (5%). Promotional posts often aimed to increase CFM awareness. Posts sharing experiences were generally positive, with the highest number of "likes"., Conclusions: Facebook groups members frequently exchanged health-related information, suggesting value placed on input from other families and the convenience of seeking information online. Posts also promoted awareness and shared experiences. Clinical care implications include the need for easily accessible accurate and tailored CFM-related health education. Additionally, providers should demonstrate awareness of health information on social media and may address the potential emotional impact of CFM by facilitating access to resources for social support., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective(s): The aim of this study was to evaluate the long-term effectiveness of costochondral graft in hemifacial microsomia (HFM) type III patients., Settings and Sample Population: A sample of 10 patients affected by HFM type III treated during growth in the same Centre with costochondral graft (CCG patients group) is compared with a control group (CG) sample of 10 non-treated patients affected by the same malformation in order to understand whether surgery during growth provides advantages in terms of bony and facial symmetry after an 8-year follow-up., Materials and Methods: The growth of the CCG was assessed on panoramic X-rays. To assess facial symmetry, a photometric evaluation on the frontal view was carried out., Results: In CCG patients group the graft grown in mean less than the healthy ramus, a good facial symmetry was achieved after surgery, but was lost in the majority of the cases at the most recent control. In CG, occlusal canting slightly increased and facial asymmetry was relatively stable during the years., Conclusion: In patients with a congenital deformity, restoring the height of the ramus leads to an immediate restitution of facial symmetry, but in the long term, there is a return to the asymmetrical pattern. In CG, the asymmetry is stable during years with no increase of the facial deformity., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. Etiology includes unknown genetic, environmental factors and chromosomal alterations, which 22q11.2 region is the most frequently reported. Several candidate genes for OAVS have been proposed; however, none has been confirmed as causative of the phenotype. This review aims to sum up all clinical and molecular findings in 22q region of individuals diagnosed with OAVS and to investigate genes that may be involved in the development of the spectrum. A search was performed in PubMed using all entry terms to OAVS and Chromosome 22q11. After screening, 11 papers were eligible for review. Deletions and duplications in the q11.2 region were the most frequent (18/22) alterations reported and a total of 68 genes were described. Our systematic review reinforces the hypothesis that 22q11 region is a candidate locus for OAVS as well as CLTCL1, GSC2, HIRA, MAPK1, TBX1, and YPEL1 as potential candidates genes for genotype-phenotype correlation. Complementary studies regarding genes interaction involved in the 22q11 region are still necessary in the search for a genotype-phenotype association, since the diagnosis of OAVS is a constant medical challenge., (© 2020 Wiley Periodicals LLC.)

Oculo-auriculo-vertebral spectrum (OAVS) [MIM:164210], or Goldenhar syndrome, is a developmental disorder associating defects of structures derived from the first and second branchial arches. The genetic origin of OAVS is supported by the description of rare deleterious variants in a few causative genes, and several chromosomal copy number variations. We describe here a large family with eight male members affected by a mild form of the spectrum, mostly auricular defects, harboring a hemizygous ZIC3 variant detected by familial exome sequencing: c.159&#95;161dup p.(Ala55dup), resulting in an expansion of the normal 10 consecutive alanine residues to 11 alanines. Segregation analysis shows its presence in all the affected individuals, with a recessive X-linked transmission. Whole-genome sequencing performed in another affected male allowed to exclude linkage disequilibrium between this ZIC3 variant and another potential pathogenic variant in this family. Furthermore, by screening of a cohort of 274 OAVS patients, we found 1 male patient carrying an expansion of 10 to 12 alanines, a variant previously reported in patient presenting with VACTERL. Loss-of-function variants of ZIC3 are causing heterotaxy or cardiac malformations. These alanine expansion variants could have a different impact on the protein and thereby resulting in a different phenotype within the OAVS/VACTERL., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: The Oculo-Auriculo-Vertebral Spectrum (OAVS) or Goldenhar Syndrome is an embryonic developmental disorder characterized by hemifacial microsomia associated with auricular, ocular and vertebral malformations. The clinical heterogeneity of this spectrum and its incomplete penetrance limited the molecular diagnosis. In this study, we describe a novel causative gene, ZYG11B., Methods: A sporadic case of OAVS was analyzed by whole exome sequencing in trio strategy. The identified candidate gene, ZYG11B, was screened in 143 patients by next generation sequencing. Overexpression and immunofluorescence of wild-type and mutated ZYG11B forms were performed in Hela cells. Moreover, morpholinos were used for transient knockdown of its homologue in zebrafish embryo., Results: A nonsense de novo heterozygous variant in ZYG11B, (NM&#95;024646, c.1609G>T, p.Glu537*) was identified in a single OAVS patient. This variant leads in vitro to a truncated protein whose subcellular localization is altered. Transient knockdown of the zebrafish homologue gene confirmed its role in craniofacial cartilages architecture and in notochord development. Moreover, ZYG11B expression regulates a cartilage master regulator, SOX6, and is regulated by Retinoic Acid, a known developmental toxic molecule leading to clinical features of OAVS., Conclusion: Based on genetic, cellular and animal model data, we proposed ZYG11B as a novel rare causative gene for OAVS., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, comprises a variable phenotype with the most common features including microtia and mandibular hypoplasia on one or both sides, in addition to lateral oral clefts, epibulbar dermoids, cardiac, vertebral, and renal abnormalities. The etiology of CFM is largely unknown. The MYT1 gene has been reported as a candidate based in mutations found in three unrelated individuals. Additional patients with mutations in this gene are required to establish its causality. We present two individuals with CFM that have rare variants in MYT1 contributing to better understand the genotype and phenotype associated with mutations in this gene., Methods/results: We conducted genetic analysis using whole-exome and -genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants. Sanger sequencing was used to confirm these mutations., Conclusion: We identified two additional individuals with CFM who carry rare variants in MYT1, further supporting the presumptive role of this gene in the CFM spectrum., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background and Objectives: Congenital microtia may be associated with hemifacial microsomia, but little is known about their correlation and development with aging. Historically, facial asymmetry is easily assessed by observing the occlusal cant using a tongue depressor. We serially measured the occlusal cant in children with microtia to evaluate change in facial asymmetry with growth., Methods: Since 2011, frontal photographs of patients with congenital microtia biting a tongue depressor were obtained and reviewed. The occlusal angle was compared between the baseline and final photographs, and the change was compared between cant-positive (>3° at baseline) and cant-negative (<3° at baseline) groups. Multivariate analysis was conducted to determine variables associated with the change in occlusal angle., Results: Overall, 105 patients were enrolled. With a mean age of 5.4 years at baseline and a mean follow-up of 3.9 years, clinically significant aggravation was observed in 15.4% and 24.2% of cant-positive and cant-negative patients, respectively. Hemifacial microsomia (OR, 4.825; p = 0.005) and occlusal angle at baseline (OR, 0.821; p = 0.045) were associated with aggravation, but the severity of microtia showed no significant association., Conclusions: When hemifacial microsomia was present, the occlusal cant seemed to be aggravated in children with microtia at later ages. When the occlusal cant was present without noticeable hemifacial microsomia, some compensation in facial asymmetry was expected. The use of a wooden tongue depressor is a simple, non-invasive, and radiologic hazard-free aid to detect notable change in facial asymmetry in children with microtia., Competing Interests: Declaration of Competing Interest None of the listed authors have anything to disclose. No funding was received for this article., (Copyright © 2020. Published by Elsevier Ltd.)

Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7-100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis and strabismus were the most reported type III anomalies, and irregular astigmatism was the most reported type IV ocular anomaly. Visual impairment in general was reported in 8-71.4% of patients, with severe visual impairment in 11.1-71.4% and amblyopia in 16.3%. This study provides a detailed overview of ocular anomalies in CFM and their prevalence. Furthermore, we propose a new classification to organize ocular anomalies into four clinically relevant subtypes. Finally, the high prevalence of ocular anomalies and visual impairment in this study suggests that CFM patients should undergo ophthalmological screening at least once during the sensitive period., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

The aim of this retrospective study was to use computer-aided design and manufacturing (CAD/CAM) patient-specific plates and cutting guides for the waferless positioning and fixation of the maxilla after bimaxillary osteotomies in cases of hemifacial microsomia with condylar dysplasia or absence of the temporomandibular joint (TMJ), and to compare the results with the CAD/CAM fabricated surgical wafer by 3-dimensional analysis. Eighteen patients were selected from the hospital database, preoperative surgical planning and simulation were done on 3-dimensional computed tomographic models for all patients, and they were divided into Group I - in which CAD/CAM patient-specific cutting guides and plates were used; and Group II - in which CAD/CAM fabricated surgical wafers were used. Finally, the outcome was evaluated by comparing planned with postoperative outcomes. The largest discrepancies of the Le Fort I segment were 0.50 (0.18) mm in the anteroposterior direction and 0.82 (0.60)° in the yaw orientation with Group I. The largest discrepancies of the Le Fort I segment were 1.32 (1.40) mm in superioinferior direction and 8.48 (7.73)° in the yaw orientation with Group II. The CAD/CAM patient-specific cutting guides and plates proved to be reliable and have great value in improving the accuracy in repositioning the Le Fort I segment and in the efficacy of orthognathic treatment of hemifacial microsomia with condylar dysplasia or no TMJ. The CAD/CAM patient-specific cutting guides and plates are therefore a useful alternative to the wafer technique., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Hemifacial microsomia (HFM) is a congenital craniofacial malformation which is associated with difficult airway. Anesthesiologists may experience difficult intubation in children with HFM. Mandibular distraction could increase the length of the mandible. Theoretically, it should be advantageous to laryngeal view during tracheal intubation. This study reviewed airway management in children with HFM, assessed the efficiency of direct laryngoscopy versus airway-visualizing equipment during the tracheal intubation and determined whether mandibular distraction could improve the laryngoscopic view in children with HFM., Methods: A retrospective review of cases involving children with HFM aged 5 to 17 years old underwent anesthesia from December 2016 to April 2019 at a single center was performed. The demographic data, preoperative airway assessments, procedure type, anesthetic technique, method of airway management, anesthetists' comments on mask ventilation, laryngoscopy and intubation parameters were collected., Results: At last, 136 HFM children entered this study, a total of 311 anesthesia procedures were completed during the study period. Face mask ventilation was possible for most of children except 1 child (bilateral involvement) required two practitioners. The success rates of intubation for the primary video laryngoscopy and fibroscopy were both 100%, but 79.5% for direct laryngoscopy (P < 0.001). 95 (38.9%) children who had difficult laryngoscopic view (DLV) were significantly correlated with failed direct laryngoscopy (P < 0.001). Airway-visualizing equipment (video laryngoscope and Fiberscope) was the primary airway technique in 3 (75%) bilaterally involved children. 60 children underwent both mandibular distraction osteogenesis and the removal of distractor. The laryngoscopic views improved in 26 (43%) children after treatment with mandibular distraction (P < 0.001)., Conclusions: Airway-visualizing equipment can be effectively utilized for intubation in HFM children with DLV. Mandibular distraction could improve the laryngeal view effectively.

Mandibular distraction osteogenesis at an early age is the standard hemifacial microsomia treatment. Nevertheless, the recurrence rate remains high and the definition of early age is controversial. We explored the optimal timing for mandibular distraction, when the surrounding skeleton, such as maxilla, can grow compensatory, to reduce recurrence. Hemifacial microsomia patients were prospectively divided into Groups A (1-3 years old) and B (4-6 years old), according to maxillary and mandibular growth curves. Computed tomography scans were obtained before distractor implantation and after removal surgery. Maxillary volume increase percentage was the main outcome indicator; other indicators (maxillary symmetry and complications) were secondary outcomes. Fifty-eight patients were enrolled and all but one patient in Group A (failed distraction) completed the study. Two patients had facial nerve injury and another two had mouth-opening limitation, which was relieved after coracoid resection. The difference in percentage increase in maxillary volume between the affected and unaffected sides was 5.06 ± 2.73% and 3.18 ± 1.99% in Groups A and B, respectively, suggesting better compensatory growth in younger patients (P = 0.004). Maxillary symmetry was apparently elevated after mandibular distraction. Mandibular distraction osteogenesis was confirmed to be feasible and safe at age <4 years., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Mandibular reconstruction in patients with hemifacial microsomia is still challenging. In this study we have introduced a costochondral graft (CCG) for reconstruction of the mandibular ramus, and reported a bone-supported osteotomy and repositioning guide system for transfer of a virtual plan. Fourteen young children with Pruzansky type III hemifacial microsomia were included and treated with CCG to reconstruct the ramus. We first made 3-dimensional models for virtual planning and simulation, with calculations for both the position and direction of the CCG, to achieve optimal morphology. We did an osteotomy and manufactured them using a 3-dimensional printing technique. Accuracy was evaluated by comparing the plan with the postoperative outcomes. The largest linear root-mean-square deviation (RMSD) between the planned and the postoperative CCG was 4.41mm in the anteroposterior direction, while the largest angle RMSD was 19.25° in the horizontal plane. We suggest that the accuracy of this new custom-made guide system is clinically acceptable for transferring the position and direction of the CCG., (Copyright © 2019. Published by Elsevier Ltd.)