BMP signaling maintains auricular chondrocyte identity and prevents microtia development by inhibiting protein kinase A.

Elastic cartilage constitutes a major component of the external ear, which functions to guide sound to the middle and inner ears. Defects in auricle development cause congenital microtia, which affects hearing and appearance in patients. Mutations in several genes have been implicated in microtia development, yet, the pathogenesis of this disorder remains incompletely understood. Here, we show that Prrx1 genetically marks auricular chondrocytes in adult mice. Interestingly, BMP-Smad1/5/9 signaling in chondrocytes is increasingly activated from the proximal to distal segments of the ear, which is associated with a decrease in chondrocyte regenerative activity. Ablation of Bmpr1a in auricular chondrocytes led to chondrocyte atrophy and microtia development at the distal part. Transcriptome analysis revealed that Bmpr1a deficiency caused a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A activation, likely through increased expression of Adcy5/8. Inhibition of PKA blocked chondrocyte-to-osteoblast transformation and microtia development. Moreover, analysis of single-cell RNA-seq of human microtia samples uncovered enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process. These findings suggest that auricle cartilage is actively maintained by BMP signaling, which maintains chondrocyte identity by suppressing osteogenic differentiation.

Electrocardiographic abnormalities in patients with microtia.

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.

Epidemiology of congenital malformations of the external ear in Hunan Province, China, from 2016 to 2020.

To describe the epidemiology of congenital malformations of the external ear (CMEE). Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016 to 2020. The prevalence of CMEEs is defined as the number of cases per 1000 fetuses (births and deaths at 28 weeks of gestation and beyond) (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ2trend) were used to determine trends in prevalence by year. P < .05 was considered statistically significant. Crude odds ratios (ORs) were calculated to examine the association of sex, residence, and maternal age with CMEEs. Our study included 847,755 fetuses, and 14,459 birth defects were identified, including 1227 CMEEs (accounted for 8.49% of birth defects). The prevalences of birth defects and CMEEs were 17.06‰ (95%CI: 16.78-17.33) and 1.45‰ (95%CI: 1.37-1.53), respectively. A total of 185 microtia-anotias were identified, accounting for 15.08% of CMEEs, with a prevalence of 0.22‰ (95%CI: 0.19-0.25). And 1042 other CMEEs were identified, accounting for 84.92% of CMEEs. From 2016 to 2020, the prevalences of birth defects were 18.20‰, 18.00‰, 16.31‰, 16.03‰, and 16.47‰, respectively, showing a downward trend (χ2trend =8.45, P < .01); the prevalences of CMEEs were 1.19‰, 1.62‰, 1.80‰, 1.21‰, and 1.35‰, respectively, with no significant trend (χ2trend =0.09, P = .77). CMEEs were more common in males than females (1.60‰ vs 1.27‰, OR = 1.26, 95%CI: 1.12-1.41), in urban areas than in rural areas (1.77‰ vs 1.23‰, OR = 1.45, 95%CI: 1.29-1.62). The prevalences of CMEEs for maternal age < 20, 20-24, 25-29, 30-34, and ≥ 35 were 1.75‰, 1.27‰, 1.44‰, 1.47‰, and 1.58‰, respectively, with no significant difference (P > .05, reference: 25-29). Most CMEEs were diagnosed by clinical examinations (92.34%), and most CMEEs were diagnosed postpartum (within 7 days) (96.25%). In summary, we have presented the epidemiology of CMEEs in Hunan Province, China. CMEEs were more common in males than females, in urban areas than rural areas, whereas there was no significant difference in prevalence of CMEEs by maternal age. We inferred that CMEEs may be mainly related to genetics, and the mechanism needs to be examined in the future.

Update on Total Auricular Construction.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand principles of preoperative planning for microtia repair. 2. Understand key techniques for flap design, skin envelope dissection, framework creation, and donor-site reconstruction. 3. Describe important components of postoperative management. SUMMARY: Total auricular construction remains a challenge for reconstructive surgeons. This article describes current surgical strategies and advancements for microtia construction. The authors' focus is to describe the several keys for success that are useful for young surgeons who wish to train themselves to create satisfactory results.

Genotype-phenotype associations in microtia: a systematic review.

BACKGROUND: Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is strong evidence that genetics has a role in the occurrence of microtia. This systematic review aimed to determine the genes involved and the abnormalities in microtia patients' head and neck regions. METHODS: We used seven search engines to search all known literature on the genetic and phenotypic variables associated with the development or outcome of microtia. The identified publications were screened and selected based on inclusion and exclusion criteria and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 papers in this systematic review with phenotypic data in microtia involving 1459 patients and 30 articles containing genetic data involved in microtia. RESULT: The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%). CONCLUSIONS: Our systematic review shows some genes involved in the microtia development, including TCOF1, SIX2, HSPA9, GSC exon 2, FANCB, HOXA2, GSC exon 3, MARS1, and CDT1 genes. We also reveal a genotype-phenotype association in microtia. In addition, further studies with more complete and comprehensive data are needed, including patients with complete data on syndromes, phenotypes, and genotypes.

Retrospective study on unilateral polyotia combined with microtia utilizing the technique of preserving residual ear tissue.

BACKGROUND: The presence of polyotia in individuals with microtia is a rare deformity. Due to the intricate structure of the auricle, uncertain etiology, and challenging corrective techniques, it has always been a focal point in the field of plastic surgery. The present study presents a technique for correcting the combination of polyotia and microtia by utilizing residual ear tissue as graft material. METHODS: The retrospective study included 23 patients with polyotia and microtia from 2018 to 2022. The residual ear tissue was used to rectify auricular deformities in all patients. The patients were instructed to evaluate the satisfaction of the auricle shape using a visual analog scale (VAS) both before and 6 months after the surgical procedure. The esthetic outcomes of auricle subunits were simultaneously assessed by a senior physician pre- and postoperatively. RESULTS: The mean duration of follow-up in this study was 8.73 months. The preoperative VAS satisfaction score was recorded as 2.26 ± 0.86, while the post-operative VAS score significantly increased to 7.86 ± 0.86. The preoperative auricle esthetic outcomes score was recorded as 9.95 ± 1.74, while the post-operative score significantly increased to 24.04 ± 2.16. The follow-up period did not present any cases of flap necrosis, hematoma, infection, or wound dehiscence. CONCLUSION: The study demonstrates that comprehensive utilization of residual auricular tissue can lead to optimal outcomes in correcting polyotia with concha-type microtia. The utilization of residual ear tissue can be maximized to streamline the operation, minimize bodily harm, and enhance patient satisfaction.

[Cochlear implantation through retro-facial approach with congenital microtia malformation with facial nerve deformity: a case report].

The difficulty of cochlear implantation in patients with congenital microtia is usually increased due to the vague anatomical marks and facial nerve malformation. The common types of facial nerve malformation include facial nerve bony cover loss, aberrant position, and bifurcation malformation. Bifurcation malformation may obscure the oval window, press against stapes, and bifurcate in the vestibular window while obscuring the round window. It is important to correctly identify the facial nerve and choose a reasonable surgical approach to avoid postoperative complications. This article describes a case of profound sensorineural hearing loss due to facial nerve malformation in our institution. The patient underwent cochlear implantation through the retro-facial approach. There was no facial nerve injury or dysfunction symptoms such as facial paralysis and hemifacial spasm 2 years after the operation, and the cochlear implant works well. The score of the categories of the auditory performance（CAP） questionnaire was 7, and the score of the speech intelligibility rating（SIR） questionnaire was 4. When the round window cannot be exposed through the facial recess approach during surgery, the retro-facial approach is a feasible method. To avoid facial nerve injury, a thin-section CT of the temporal bone should be performed before the middle and inner ear surgery for patients with facial nerve malformation, and the intraoperative facial nerve monitor should be used to clarify the course of the facial nerve to avoid injury.

Perioperative position management of 46 cases with simultaneous bilateral auricle reconstruction: A summary of experience.

OBJECTIVES: The primary problem in simultaneous bilateral auricle reconstruction is the fragility of the reconstructed ear structure. Postoperative pressure is strictly prohibited to ensure the operation's effectiveness. The study aimed to summarize the experience of perioperative postural management in simultaneous bilateral auricular reconstruction. METHOD: This study summarizes the experience of perioperative postural management, providing preoperative sleeping posture adaptability training, neck movement training, standardization of the head position angles and the head suspension time in surgery, using protective headrests, paying attention to the transfer and handover procedures, and using specially designed pillows. RESULTS: The comprehensive nursing approach in simultaneous bilateral auricular reconstruction significantly reduced complications, improved patient comfort, and optimized postoperative adaptation. Preoperative posture training, standardized intraoperative head positions, and vigilant postoperative care played pivotal roles, demonstrating positive outcomes in 46 cases. DISCUSSION: Perioperative position management can reduce the risk of complications and pressure injuries, improving patients' postoperative comfort, emotional state, tolerance, and adaptability. CONCLUSION: All ears were viable and in good shape after long-term follow-up. The experiences discussed in this study can be broadly applied to technically mature ear reconstruction teams.

Prograde transposition for anteriorly low-set earlobe in lobule-type microtia reconstruction.

BACKGROUND: Lobule transposition, a common procedure in auricle reconstruction, has been successfully performed over the past few decades. However, the transposition methods for unilateral microtia with evident asymmetry of bilateral earlobe positions still remain a challenge. The objective of this study was to investigate the application of prograde transposition for anteriorly low-set earlobes. METHOD: A total of 25 patients with lobule-type microtia with anteriorly low-set residual earlobe underwent prograde transposition during auricle reconstruction between 2020 and 2022. The post-operative earlobe aesthetic assessment and patient satisfaction were evaluated, and the data on any complications that occurred when followed-up were collected. This study provides a comprehensive analysis and summary of the techniques used in earlobe transposition for auricular reconstruction. RESULTS: The patients with evident asymmetry between the residual and healthy earlobes were usually concomitant with hemifacial microsomia and the residual ear was located in the anterior and lower region. No instances of flap necrosis, hematoma, or wound dehiscence were observed following auricular reconstruction. The mean aesthetic score of the auricle was 3.52, with 23 patients attaining good or excellent aesthetic outcomes. The mean Visual Analog Scale satisfaction score was 3.68, with 24 patients reporting relative satisfaction or satisfaction. CONCLUSION: The prograde transposition of anteriorly low-set earlobe in lobule-type microtia reconstruction can effectively ensure adequate blood supply, enhance aesthetic appearance, and significantly improve patient satisfaction.

Comparing the Analgesic Effects Between the Pre- and Post-costal Cartilage Harvest Cohorts Using Ultrasound-Guided Deep Serratus Anterior Plane Block in Children with Microtia Undergoing Auricular Reconstruction: A Randomized Clinical Trial.

PURPOSE: Pain following costal cartilage harvest surgery is the most common complaint of auricular reconstruction (AR). Anesthesiologists are continuously searching for an effective postoperative pain control method. METHODS: This study was conducted from 10 April 2022 to 10 June 2022. Sixty children undergoing AR using costal cartilage were randomly assigned to either a serratus anterior plane block performed before costal cartilage harvest (SAPB-pre-cohort; n = 30) or the SAPB-post-cohort (Post-costal cartilage Harvest Cohort: n = 30). The primary endpoint measures were the Numerical Rating Scale (NRS) scores of the chest and ear pain degrees recorded at 1-, 6-, 12-, 24-, and 48-h after surgery. Intraoperative anesthetic and analgesic dosages, sufentanil consumption and rescue analgesia consumption during the first 24 h post-operation, cough score during extubation, extubation agitation score, length of stay, the extubation time, first ambulatory time, analgesia duration, and opioid-related adverse effects and SAPB-related adverse effects were the secondary endpoints. RESULTS: The rest and coughing NRS scores were significantly reduced in the SAPB-pre-cohort 6 and 12 h post-operation in comparison with the SAPB-post-cohort (rest 6 h p = 0.002, others p < 0.001). No significant difference in the NRS ear scores existed between the two cohorts (p > 0.05). The use of propofol and remifentanil for general anesthesia during the SAPB-pre-procedure was significantly reduced compared to the SAPB-post-group, with statistical significance (p < 0.001). Sufentanil consumption and rescue analgesia consumption were significantly reduced in the SAPB-pre-cohort (p = 0.001, p = 0.033). The extubation time and first ambulatory time were markedly shorter in the SAPB-pre-cohort (all p < 0.001). Analgesia duration was markedly longer in the SAPB-pre-cohort (p < 0.001). No significant differences were noted in the cough score during extubation, extubation agitation score, length of stay between the two cohorts (all p > 0.05). Opioid-related adverse effects occurred more in the SAPB-post-cohort, while there was no statistical significance (16.7 vs. 36.7%; p = 0.082). There were no blockade-related complications observed in either cohort. CONCLUSION: The analgesic effect of the SAPB-pre-cohort was better than the SAPB-post-cohort suggesting both efficacy and feasibility of preemptive analgesia. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Anatomical variant of the superficial temporal artery in temporoparietal fascia flap for microtia reconstruction.

BACKGROUND: Single-stage microtia auricular reconstruction is becoming more relevant. The determining factor is a temporoparietal fascia flap (TPF) with both branches of the superficial temporal artery (STA). There are not many studies regarding vascular branching in people with microtia. METHODS: We conducted an anatomical study on the TPF flap harvested during single-stage endoscopic-assisted microtia auricular reconstruction from May 2018 to July 2021. We observed the flaps under endoscopic and surgical microscopes to determine several variables (vascular size, number of frontal/parietal branches, distance from the branching location to the estimated external ear canal, distance from the frontal artery to projected course of facial nerve's frontal branch, etc.). RESULTS: The study included 55 flaps from 54 patients. Of the 55 flaps, 50 (90.9%) had a parietal branch, and all 55 (100%) had a frontal branch with a mean diameter of 0.98 and 0.91 mm, respectively. Regarding the frontal artery, 1.8%, 25.5%, 50.9%, 16.35% and 5.45% had 0-4 traverse frontal branch(es), respectively. The mean distance from the frontal artery to the estimated course of the frontal nerve was 10.56 mm. Parietal artery absence is more likely in patients with severe hemifacial microsomia or STA trunk go under the auricular cartilage remnants (p < 0.05). Either frontal or parietal artery absence or small diameter can cause necrosis. Frontal arteries travelling near the frontal nerve may result in post-operative nerve palsy. CONCLUSIONS: Microtia auricular reconstructive surgery is always a big challenge for plastic surgeons. Anatomical variants are common. A detailed anatomical description of the STA, with the help of microsurgery and endoscopy, allows arterial-based flap designing and harvest, which tremendously improves surgical success rate by diminishing flap necrosis and nerve damage. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Effects of Radial Cartilage Incision on the Growth of Rabbit Ear.

OBJECTIVES: Recently, radial cartilage incision (first-stage) at an early age combined with free auricular composite tissue grafting (second-stage) can effectively correct the concha-type microtia with the moderate or severe folded cartilage in the middle and upper third auricle, but radial cartilage incision's effects on the growth of the ear remain to be determined. The authors aimed to evaluate the effects of radial cartilage incision in young rabbits model. METHODS: Ten New Zealand white rabbits were included in our experiment. Two ears of each rabbit were divided randomly into two groups. The experimental group was operated with radial cartilage incision, and no intervention was given to the control group. The ear width, length, and perimeter were noted every two weeks. Auricular surface area was noted at 4 and 22 weeks old. The repeated measures ANOVA was used to describe ears' growth trend. A paired-sample's t test is conducted to test whether there are significant differences among the variables through the SPSS25.0 software. RESULTS: The growth tendencies of the ear length, width, and perimeter were observed and analyzed. The growth curves of the experimental ears were similar to that of the control. There was no significant difference in the increased ratio of surface area among the two groups. The cartilage of the experimental ears showed no change in biomechanical properties compared to that of control group. CONCLUSION: This study shows that radial cartilage incision at an early age does not influence the growth of rabbit ear length, width, perimeter, and surface area and also does not change the biomechanical properties of the cartilage. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

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.

[CT features of abnormally whole-course wide eustachian tubes with microtia and atresia].

Objective: To study the clinical and CT features of the abnormal whole-course wide of eustachian tube (AWWET) with microtia and atresia(MA). Methods: The clinical and CT data of 19 patients (20 ears) from January 2017 to December 2021 with AWWET with MA were retrospectively analyzed, including 15 males and 4 females. The age ranged from 5 to 16 years, with an average of 9.5 years. 50 patients with common MA without wide eustachian tube(ET) as a case control group, including 32 males and 18 females.The age ranged from 5 to 16 years, with an average of 9.2 years. 20 patients (40 ears) who had normal ear CT for tinnitus, otalgia as a normal control group, including 12 males and 8 females. The age ranged from 5 to 16 years, with an average of 12.5 years. We measured the dimension and length of the bony portion of the ET, the total length, the angle between the bony portion and the cartilage portion, and the horizontal angle of ET on CT imagings, and compared with 40 normal ears by SPSS 27.0 software. Results: According to the relationship between AWWET and tympanum, patients were divided into the communicated group and the blocked group. A male predominance, left ear predominance, with high incidence of hemifacial microsomia exhibited in both groups. AWWET was presented as a widened lumen on CT. In 11 ears (4 ears in the communicated group, 7 ears in the blocked group), ETs bifurcated, the upper bony tube extended to the sphenoid body, the lower part continued down to cartilaginous ET and opened onto the nasopharynx, with"mastoid-like"pneumatization of the sphenoid body in 6 ears. The middle ear deformity in case group was more serious than MA control group, especially the blocked group. The incidence of otitis media in the communicated group was lower than that in the MA control group, and 4 cases in the blocked group had effusion in the ET. Compaired with normal ear, the bony ET elongated significantly in the AWWET groups, and the whole course of ET was significantly shortened, specially in the blocked group. The angle between the bony ET and the cartilaginous ET was decreased and the horizontal angle of the ET increased in the AWWET groups, the difference was considered to indicate statistical significance(P<0.05). Conclusions: AWWET with MA is rare, a male predominance, left ear predominance, and with high incidence of hemifacial microsomia. The middle ear deformity is more serious than common MA, especially in the blocked group. The incidence of otitis media in the communicated group is significantly lower than that in the common MA, and the blocked group may be accompanied by ET inflammation.

A 76-base pair duplication within the enhancer region of the HMX1 gene causes sheep microtia.

Sheep congenital microtia is characterized by underdeveloped ears and provides an ideal basis for studying human microtia. This study identified the causal mutation and regulatory mechanisms underlying this disorder. Whole-genome association analysis was conducted using 23 ear tissue samples from sheep with microtia and 28 samples from normal-eared sheep. A significant correlation was found between microtia and a 76-base pair duplication in the enhancer region of the HMX1 gene. Further analysis of offspring phenotypes confirmed an autosomal dominant inheritance pattern. Genotypic analysis showed that individuals that are homozygous for this duplication were earless, heterozygous individuals exhibited shortened ears, and wild-type individuals had normal ears. Moreover, luciferase assays confirmed that this duplication increased HMX1 gene expression, and duplication knock-in mice also exhibited shorter and narrower external ears compared to wild-type mice. Transcriptomic analysis further demonstrated that this duplication enhanced HMX1 gene expression in animal models. This study characterized the causal regulatory mutation underlying sheep microtia.

Profiling of Long Non-Coding RNAs in Auricular Cartilage of Patients with Isolated Microtia.

Introduction: Microtia is the second most common maxillofacial birth defect worldwide. However, the involvement of long non-coding RNAs (lncRNAs) in isolated microtia is not well understood. This study aimed at identifying lncRNAs that regulate the expression of genes associated with isolated microtia. Methods: We used our microarray data to analyze the expression pattern of lncRNA in the auricular cartilage tissues from 10 patients diagnosed with isolated microtia, alongside 15 control subjects. Five lncRNAs were chosen for validation using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 4651 differentially expressed lncRNAs in the auricular cartilage from patients with isolated microtia. By Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analysis, we identified 27 differentially expressed genes enriched in pathways associated with microtia. In addition, we predicted 9 differentially expressed genes as potential cis-acting targets of 12 differentially expressed lncRNAs. Our findings by qRT-PCR demonstrate significantly elevated expression levels of ZFAS1 and DAB1-AS1, whereas ADIRF-AS1, HOTAIRM1, and EPB41L4A-AS1 exhibited significantly reduced expression levels in the auricular cartilage tissues of patients with isolated microtia. Conclusions: Our study sheds light on the potential involvement of lncRNAs in microtia and provides a basis for further investigation into their functional roles and underlying mechanisms.

Analysis of predictive factors related to long-term hearing and temporal bone development in congenital microtia.

OBJECTIVE: To investigate the predictive factors of long-term hearing threshold and temporal bone development in children with congenital microtia (CM). METHODS: 74 patients (92 ears) with CM enrolled, which all had auditory brainstem response (ABR) results during infancy or toddlerhood, pure tone audiometry (PTA) and high-resolution computed tomography (HRCT) results during childhood or adolescence, and had not undergone any surgery. We compared the relationship between ABR, auditory steady-state response (ASSR), the affected side, auricular morphology, presence of external auditory canal stenosis or atresia, PTA average, mastoid pneumatization, Jarhsdoerfer scores, and wether cholesteatoma exists. RESULTS: The average age of ABR in 92 ears was 2.72 ± 3.52 years old, PTA was 7.26 ± 2.51 and HRCT was 6.91 ± 2.76 years old. ABR-AC was related to PTA average, mastoid pneumatization, Jarhsdoerfer scores, and wether cholesteatoma exists in CM. While ABR-ABG was related to all of these factors except Jarhsdoerfer score, and ABR-BC had no relationship with any of them. ASSR only showed correlation with frequencies of 1, 2 kHz and was related to Jarhsdoerfer score, with no other correlations observed. The impaired ear side showed no relevance. However, auricular morphology was related to all of these factors except wether cholesteatoma exist. External auditory canal stenosis or atresia was related to PTA average, but unrelated to mastoid pneumatization. CONCLUSION: The ABR examination in the infant stage plays a crucial role in predicting the long-term hearing and temporal bone development in patients with CM.

Suitability of Ex Vivo-Expanded Microtic Perichondrocytes for Auricular Reconstruction.

Tissue engineering (TE) techniques offer solutions for tissue regeneration but require large quantities of cells. For microtia patients, TE methods represent a unique opportunity for therapies with low donor-site morbidity and reliance on the surgeon's individual expertise. Microtia-derived chondrocytes and perichondrocytes are considered a valuable cell source for autologous reconstruction of the pinna. The aim of this study was to investigate the suitability of perichondrocytes from microtia patients for autologous reconstruction in comparison to healthy perichondrocytes and microtia chondrocytes. Perichondrocytes were isolated via two different methods: explant culture and enzymatic digestion. The isolated cells were analyzed in vitro for their chondrogenic cell properties. We examined migration activity, colony-forming ability, expression of mesenchymal stem cell markers, and gene expression profile. We found that microtic perichondrocytes exhibit similar chondrogenic properties compared to chondrocytes in vitro. We investigated the behavior in three-dimensional cell cultures (spheroids and scaffold-based 3D cell cultures) and assessed the expression of cartilage-specific proteins via immunohistochemistry, e.g., collagen II, which was detected in all samples. Our results show that perichondrocytes from microtia patients are comparable to healthy perichondrocytes and chondrocytes in terms of chondrogenic cell properties and could therefore be a promising cell source for auricular reconstruction.

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/ß-Catenin Pathway.

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.