GATA3 is essential for separating patterning domains during facial morphogenesis.

Neural crest cells (NCCs) within the mandibular and maxillary prominences of the first pharyngeal arch are initially competent to respond to signals from either region. However, mechanisms that are only partially understood establish developmental tissue boundaries to ensure spatially correct patterning. In the 'hinge and caps' model of facial development, signals from both ventral prominences (the caps) pattern the adjacent tissues whereas the intervening region, referred to as the maxillomandibular junction (the hinge), maintains separation of the mandibular and maxillary domains. One cap signal is GATA3, a member of the GATA family of zinc-finger transcription factors with a distinct expression pattern in the ventral-most part of the mandibular and maxillary portions of the first arch. Here, we show that disruption of Gata3 in mouse embryos leads to craniofacial microsomia and syngnathia (bony fusion of the upper and lower jaws) that results from changes in BMP4 and FGF8 gene regulatory networks within NCCs near the maxillomandibular junction. GATA3 is thus a crucial component in establishing the network of factors that functionally separate the upper and lower jaws during development.

Prenatal findings in 11 cases with craniofacial microsomia using the Alberta Congenital Anomalies Surveillance System, 1997-2019.

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.

Goldenhar syndrome with limbal neoformation, microtia and skeletal deformities: a case report and literature review.

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.

Management of sleep-disordered breathing in patients with syndromic hemifacial macrosomia.

PURPOSE: Patients with syndromic hemifacial microsomia (SHFM) are at risk of obstructive sleep apnea (OSA). The aim of the study was to describe the prevalence of OSA and its management, especially in patients with Goldenhar syndrome (GS). METHODS: The respiratory polygraphies and clinical management of 15 patients, aged 2 to 23 years, evaluated at a national reference center, were analyzed. RESULTS: Four (27%) patients had no OSA, 4 (27%) had mild OSA, and 7 (46%), of whom 5 were ≤ 2 years old, had severe OSA. None of the patients had central apneas. Only one patient had alveolar hypoventilation, and another one had nocturnal hypoxemia. Two patients had severe OSA despite prior adenoidectomy or mandibular distraction osteogenesis. Median duration of follow-up was 3.5 years (range 0.5-9 years). None of the patients without OSA or with mild OSA at baseline respiratory polygraphy developed OSA during the follow up. Among the 7 patients with severe OSA, 3 required continuous positive airway pressure or noninvasive ventilation, and one patient required a tracheostomy. CONCLUSION: In conclusion, patients with SHFM are at high risk of severe OSA at any age, underlining the importance of systematic sleep studies to diagnose and evaluate the severity of OSA. Individualized treatment should be privileged, based on a careful examination of the entire upper airway, taking in account potential associated risk factors. All patients with SHFM should be managed by a pediatric expert multidisciplinary medical/surgical team until the end of post pubertal growth.

Total temporomandibular joint reconstruction prosthesis in hemifacial microsomia: A systematic review.

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.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

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.

Three-dimensional Analysis of the Temporal Bone Morphology in Patients with Craniofacial Microsomia.

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.

Craniofacial Microsomia, Associated Congenital Anomalies, and Risk Factors in 63 Cases from the Alberta Congenital Anomalies Surveillance System.

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.

Hemifacial microsomia is linked to a rare homozygous variant V162I in FRK and validated in zebrafish.

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.

The etiology, clinical features, and treatment options of hemifacial microsomia.

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.

Management of unilateral craniofacial microsomia with orthopaedic functional appliances: A systematic literature review.

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.

Analysis of Obstructive Sleep Apnoea in Craniofacial Microsomia Based on Polysomnography.

OBJECTIVE: This study aimed to investigate the prevalence of obstructive sleep apnoea (OSA) in patients with craniofacial microsomia (CFM) through polysomnography (PSG) and the relationship with the severity of CFM. METHODS: This study reviewed patients of CFM with pre-operative PSG data between January 2005 and September 2023. Patients were grouped according to the Pruzansky-Kaban classification. OSA was diagnosed and severity was assessed by the obstructive apnea-hypopnea index. The Pediatric Sleep Questionnaire was used to investigate OSA-related signs and symptoms. The χ 2 test and Fisher's exact test were used to compare between groups. Univariate logistic regression was used to identify risk factors associated with OSA. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 121 patients with CFM were included in the study with 3 bilateral and 118 unilateral patients. In total, 86 patients (71.07%) were diagnosed with OSA. The prevalence of OSA in type IIa, type IIb and type III was 72.97%, 78.33%, and 47.62%. There was no statistically significant difference in the prevalence of OSA between type IIa and type IIb (p > .05). The difference in the prevalence of OSA between type III and type II was statistically significant (p < .05). Snoring was the most common symptom among the patients of CFM with OSA. CONCLUSIONS: Patients with CFM have a higher incidence of OSA based on PSG in type II and type III patients. The incidence of OSA did not correlate positively with the severity of CFM, with type III patients having certain particularities.

Longitudinal Skeletal Growth Analysis of Mandibular Asymmetry in Unoperated Patients With Unilateral Craniofacial Microsomia (UCFM).

PURPOSE: To examine the growth rate discrepancy of the affected and unaffected ramus heights in Pruzansky Type I and Type II mandibles. METHODS: This is a serial retrospective longitudinal growth study of 30 untreated patients (21 males and 9 females) with UCMF (age range from 5 years to 14 years). The mean age of patients was 8.5 years, and the mean follow-up records were 3.7 years. There were 13 patients in group I with a Pruzansky Type I mandible and 17 patients in group II with a Pruzansky Type II. The unaffected side of the mandible served as a control. Eighteen cephalometric parameters were examined at each of the two-time intervals. RESULTS: In patients with Pruzansky Type I mandible, the affected ramus grew on average 1.41 mm per year; the unaffected ramus grew 1.66 mm per year during the same period. In patients with Pruzansky Type II mandible, the affected ramus grew on average 0.84 mm per year; during the same period, unaffected ramus grew 1.79 per year. When the growth rate of the ramus height on the affected side was compared to the unaffected side, there was no statistically significant difference in Pruzansky Type I mandibles (p > .05); however, there was a statistically significant difference in the Pruzansky Type II mandibles (p < .05). CONCLUSION: The growth rate discrepancy of the affected and unaffected ramus heights was more severe in Pruzansky Type II mandibles than Pruzansky Type I mandibles explaining the progressive nature of facial asymmetry in Pruzansky II mandibles.

Bone Density of the Condyle of Children with Craniofacial Microsomia and its Correlation with Condylar Resorption After Mandible Distraction Osteogenesis.

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.

A 3-Dimensional Evaluation of the Effects of Unilateral Vertical Mandibular Distraction Osteogenesis on Airway Volume Among Patients With Hemifacial Microsomia.

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.

Interrater Reliability for Classifying Craniofacial Microsomia Severity: A Call for Objective Evaluation.

OBJECTIVE: The severity of craniofacial microsomia (CFM) is generally classified using the Orbit, Mandible, Ear, Soft tissue, Nerve (OMENS) classification score. The global assessment of the Phenotypic Assessment Tool for Craniofacial Microsomia (PAT-CFM), is a pictorial modification of the OMENS classification. The aim of this study was to assess the interrater reliability of the PAT-CFM global assessment score. DESIGN: In this prospective cohort study, three clinicians completed the global assessment form of the PAT-CFM. The mandible was classified based on orthopantomogram- and/or computed tomography images. PARTICIPANTS: Consecutive patients with CFM or microtia.Interrater agreement was calculated using the weighted Krippendorff alpha (α), with 95% confidence intervals (CI). RESULTS: In total, 53 patients were included (106 hemifaces). The reliabilities of the main classification components ranged from high for the mandible (α = 0.904 [95% CI 0.860-0.948]) and ear (α = 0.958 [95% CI 0.934-0.983]) subscales, to tentative for the orbital summary score (α = 0.682 [0.542-0.821]), and nerve summary score (α = 0.782 [0.666-0.900]) subscales. CONCLUSIONS: The reliability of the ear and radiographic mandible scales of the PAT-CFM global classification were high, while the orbit, facial nerve and soft tissue subscales may have limited reliability. Research focusing on radiographic severity scores for hypoplasia of the orbits and soft tissues, as well as objective measures for overall facial hypoplasia using non-ionizing forms of imaging for early classification, are warranted.

To Operate or Not to Operate? Reconstructive Surgical Burden and Quality of Life of Pediatric Patients with Facial Differences.

OBJECTIVE: The Craniofacial Condition Quality of Life Scale (CFC-QoL) was used to evaluate the relationship between surgical burden and quality of life (QoL). DESIGN: Patient-parent dyads completed the CFC-QoL which queries the following QoL domains: Bullying, Peer Problems, Psychological Impact, Family Support, Appearance Satisfaction, and Desire for Appearance Change. Stepwise multivariate linear regressions were performed for each QoL domain. SETTING: Urban tertiary care center. PATIENTS, PARTICIPANTS: Pediatric patients with facial differences, and their parents. INTERVENTION: Survey study. MAIN OUTCOME MEASURE(S): Demographic, diagnostic, and surgical characteristics were collected. Surgical burden was calculated as the standard deviation from the mean number of surgeries per diagnostic cohort. RESULT: Patients (N = 168) were majority female (57.1%) and Hispanic (64.3%). Diagnoses were cleft lip and/or palate (CLP,n = 99) or other craniofacial conditions (CFC,n = 69). Average patient age was 2.3 ± 5.6 years at first reconstructive surgery and 12.3 ± 3.4 years at study enrollment. Patients received an average of 4.3 ± 4.1 reconstructive surgeries.Worse Bullying was associated with higher surgical burden. Worse Peer Problems was associated with higher surgical burden, but only for children with non-CLP CFCs. Worse Family Support was associated with CFC diagnosis, female sex, and higher surgical burden. Worse Psychological Impact was associated with higher surgical burden. Worse Appearance Satisfaction was associated with younger age and with lower surgical burden. Greater Desire for Appearance Change was associated with older age, higher surgical burden, CLP diagnosis, female sex, and non-Hispanic ethnicity. Socioeconomic status did not predict QoL per patient self- or parent-proxy report. CONCLUSIONS: Higher surgical burden was associated with worse QoL outcomes in multiple domains.

Tessier's Cleft Number 6 Revisited: A Series of 26 new Cases and Literature Review of 44.

OBJECTIVE: To fix a gray zone left in Tessier's classification of rare clefts with cleft 6 and to give a more comprehensive description of cleft 6 anatomy. DESIGN: The material used for the research was a series of 26 clinical cases of patients with assessed cleft 6 and 44 cases found out of a literature review with enough data to be useful. The 70 cases were cross-examined by the authors. STUDY SETTING: The authors are senior craniofacial surgeons working in high-case load department from university centers where the patients are documented and receive primary as well as secondary treatment and follow-up. PATIENTS: The patients were selected out of the series of craniofacial deformities taken care of by the authors' department as rare clefts. MAIN OUTCOME: We describe the full spectrum of cleft 6 as an autonomous entity that could present itself in three subtypes: 6a is the most proximal and could be associated with cleft 8. The subtype 6b is medial toward the zygomatic arch and frequently associated with a bone and teeth appendage (frequently described as a "maxillary duplication"). The subtype 6C goes toward the external ear between the helix crus and the auditory meatus. CONCLUSIONS: The Tessier's opinion is that Treacher Collins syndrome was the association of clefts 6, 7, and 8 and is no longer sustainable in the light of modern genetics. Most of the cleft 6 are misdiagnosed in the literature.

Effects of mandibular distraction osteogenesis on anesthetic implications in children with hemifacial microsomia.

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.

Expanding the Etiology of Oculo-Auriculo-Vertebral Spectrum: A Novel Interstitial Microdeletion at 1p36.

The etiology of oculo-auriculo-vertebral spectrum (OAVS) is not well established. About half of patients show a positive family history. The etiology of familiar cases is unclear but appears genetically heterogeneous. This motivated us to report a case of OAVS with microtia, ptosis, facial microsomy, and fusion of vertebral bodies associated with a novel genetic etiology, including a deletion at 1p36.12-13. This case report expands on the genetic etiology of OAVS. Furthermore, it also expands the clinical manifestations of patients with interstitial deletions of the de 1p36.12-13 region.