Inheritance analysis and family history for microtia: A hospital-based study in China.

OBJECTIVES: Microtia is a congenital anomaly of the outer ear. Although genetic and environmental factors could play a role, no consensus has been established on the pathogenesis and cause of this condition. In this study, we surveyed the frequency and pattern of family history in patients with microtia in a Chinese specialty clinic population. METHODS: We evaluated data from 672 patients (mean age = 9.2, male-to-female ratio = 2.6:1) with microtia admitted to the Department of Auricular Reconstruction at the Plastic Surgery Hospital of Peking Union Medical College from December 2014 to February 2016. Family history of congenital ear anomalies across three generations was recorded. Pearson chi-square test or Fisher exact test was used to test the associations between the characteristics of microtia and hereditary features. RESULTS: A family history of auricle anomalies was identified in 202 patients (30.1%), of whom, 95 families showed vertical transmission, 14 families skipped a generation, and 120 families showed family aggregations. The incidence of family history varied with grades of microtia (P = 0.001). Patients with preauricular tags or pits (38.3%) had a higher familial incidence of microtia than those with simple microtia (24.1%) (P < 0.001). CONCLUSION: Patients with a lower grade of microtia demonstrated a higher incidence of family history. Patients with microtia had significantly more relatives with preauricular tags or pits. Microtia and preauricular tags or pits are different manifestations of the same defect, and their significant concurrency among relatives suggests that a considerable proportion of microtia is inherited and could recur with varying degrees of severity in other family members.

Functional Pathway and Process Enrichment Analysis of Genes Associated With Morphological Abnormalities of the Outer Ear.

Congenital anomalies of the outer ear are common birth defects, including a variety of congenital deformities or malformations ranging from mild structural anomalies to total absence of the ear. Despite its high incidence and detrimental impact on patients, the etiology of outer ear abnormalities remains poorly understood. The goal of this study was to summarize the related genes and improve our understanding of the genetic etiology of morphological abnormalities of the outer ear. Human Phenotype Ontology (HPO) database, Mouse Genome Informatics (MGI) database, and PubMed search engine were used to acquire the genes associated with abnormal human or mouse outer ear. Metascape was employed on the genes above to conduct functional annotation, pathway and process enrichment analysis, protein-protein interaction network analysis, and MCODE component analysis. After a comprehensive review of the databases and literature, we identified 394 human genes and 148 mouse genes that have been associated with abnormal phenotypes of the outer ear, and we identified several biological pathways for human and mouse respectively. Especially, the analysis of common genes shared by human and mouse emphasized the importance of certain genes ( PAX6 , PBX1 , HOXA1 , HOXA2 , TBX1 , TBX15 , PRRX1 , and HMX1 ) in the embryonic development of the external ear. Through our analysis of genes associated with morphological abnormalities of the outer ear, the authors have shown that embryonic development pathways take important roles in the morphogenesis of abnormal external ear and highlighted some potential genetic drivers.

A novel method to accurately locate the reconstructed auricle.

Background: Congenital microtia is a common congenital disease in children, the cause of which is still unclear. At present, the main treatment for congenital microtia is ear reconstruction. Accurately locating of the reconstructed ear on the affected side before ear reconstruction surgery is difficult, while it is the key of successful operation. Our ear reconstruction team has developed a novel method to accurately locate the reconstructed auricle. This novel method has achieved good results in clinical practice. Methods: Thirty patients with unilateral ear reconstruction, who underwent auricle reconstruction using our invented auricle reconstruction positioning method in the Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2020 to July 2021, were enrolled in this study. Results: Through Wilcoxon signed rank test, we found that there was no statistical difference between the mean distance from the highest point of the patient's normal ear to the central axis of the nose and that from the highest point of the reconstructed ear to the central axis of the nose (P>0.05). Meanwhile, there was no statistical difference between the mean distance from the lowest point of the patient's normal ear to the central axis of the nose and that from the lowest point of the reconstructed ear to the central axis of the nose (P>0.05). The satisfaction rate of patients and their families to the location of the reconstructed auricle was 100%. Conclusions: The novel method of locating the reconstructed auricle employs simple materials. The implementation process is easy, and the effect is significant. To a certain extent, it solves the difficulty of locating the reconstructed auricle in ear reconstruction operation. Although this method can only be applied to patients with unilateral microtia, we recommend it for locating the reconstructed auricle by every plastic surgeon.

Classification and Surgical Strategies of Constricted Ears in a Chinese Specialty Clinic: A Retrospective Study.

BACKGROUND: The constricted ear is an auricular deformity produced by a deficiency in the circumference of the helical rim. The classification and corrective methods for constricted ears continue to be controversial. In order to identify them, the authors have reviewed and analyzed cases operated in a Chinese specialty clinic. METHODS: Correction of constricted ears from January of 2017 to June of 2021 was retrospect through medical records. Data of patients' variables (including sex, age, laterality, type of constricted ear, presence of other ear anomalies), surgical techniques, esthetic outcomes, and postoperative complications have been collected. RESULTS: The deformed ears were classified into four graded types by three criteria including deficiency of auricle cartilage, vertical height in dorsal view, and surgical outcome. A total of 68 constricted ears of 57 patients (type I, n = 6; type IIA, n = 41; type IIB, n = 19, and type III, n = 2) were enrolled in the study. Of the 66 constricted ears undergoing surgical correction, most of them were performed with helical expansion through auricular/costal cartilage graft, Mustardé-type mattress sutures, and tumbling cartilage flap. External molding using Vaseline gauze rolls was implemented on every case to assist reshaping the scapha. A triangular superficial temporal fascial flap was elevated to prevent the reoccurrence of lidding in some cases. Corrective techniques and esthetic outcomes for deformed cases of each graded type were described. Based on a four-point Likert scale, the average esthetic outcome score was 3.7. CONCLUSIONS: The classification was practical and the constricted ears were effectively corrected by simple surgical procedures without removal of deformed auricular cartilage. All corrections were performed in one stage. LEVEL OF EVIDENCE IV: 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 .

Comparison of Auricle Reconstruction Using Tissue Expanders With Skin Grafting and Auricle Reconstruction Using Tissue Expanders Without Skin Grafting: A Single-Arm Meta-Analysis.

OBJECTIVE: The authors conducted this meta-analysis to compare the efficacy of auricle reconstruction using tissue expanders with skin grafting and auricle reconstruction using tissue expanders without skin grafting by comparing the 6 major evaluation indicators. METHODS: The databases such as PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP information databases were searched. RESULTS: By comparison, the authors found that, the satisfaction rate, the incidence of postoperative hematoma, the incidence of postoperative incision infection, and the incidence of cartilage framework exposure of patients with auricle reconstruction using tissue expanders with skin grafting were all lower than those with auricle reconstruction using tissue expanders without skin grafting. However, the incidence of postoperative skin necrosis, the incidence of leakage or exposure of expanders in patients with auricle reconstruction using tissue expanders with skin grafting were all higher than those with auricle reconstruction using tissue expanders without skin grafting. CONCLUSIONS: Auricle reconstruction using tissue expanders with skin grafting has advantages in reducing the incidence of postoperative hematoma, the incidence of postoperative incision infection, and the incidence of cartilage framework exposure. Auricle reconstruction using tissue expanders without skin grafting has advantages in improving the satisfaction rate, reducing the incidence of postoperative skin necrosis, and the incidence of leakage or exposure of expanders. From the comparison of specific data, there is no significant difference in the treatment effect between the 2 surgical methods.

Heterogeneity of Accompanying Phenotypes and Genomic Variants Involved in Microtia.

OBJECTIVES: The symptoms associated with microtia are ever-changing and not to stick to 1 pattern. The symptoms associated with microtia are constantly changing and are not set in stone. The aim of this article was to describe the various phenotypes from multiple systems found in microtitis patients included in the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources database, and to analyze possible pathogenic mutations. METHODS: DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources is an interactive web-based database, which incorporates a suite of tools designed to aid the interpretation of genomic variants. The term "microtia" was used as the search term, and the data extracted from the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources for this study was updated until October 2020. Pearson chi-squared test was used to test associations between types of genomic variants and the pathogenicity of variants. RESULTS: Of the 386 cases enrolled in the study, 99% (n = 382) had 1 or more associated abnormalities. The most frequently detected abnormalities were those of the face and neck (n = 362 [93.8% of all cases]); musculoskeletal system (n = 337 [87.3%]); and nervous system (n = 334 [86.5%]), followed by abnormalities of limbs (n = 252 [65.3%]); the eye (n = 212 [54.9%]); and the integument (n = 200 [51.8%]). Besides, a total of 479 genomic variants were determined, including sequence variants and copy number variants (loss and gain). The pathogenicity of loss-type variants was significantly higher among other types (P < 0.001). Twelve sharing variants had more than 5 repeats, and the repeated fragments were concentrated on chromosome 3, 7, 9, 10, 11, 15, 17, 18, and 22. CONCLUSIONS: Identification of the relation between phenotypes and genotypes will facilitate the uncovering of the mechanism of microtia and the study of potential therapeutic targets.

The morphological changes of thorax in pediatric microtia patients after costal cartilage harvesting.

BACKGROUND: The surgical treatment of microtia generally starts in childhood, and costal cartilage is the most widely used material for auricular reconstruction. However, multiple costal cartilage harvests lead to local cartilage defects, which may influence the growth of the hemithorax, that need close attention by doctors. In this study, morphological changes of the thorax were measured and analyzed in different follow-up groups. METHODS: Twenty-eight adolescent microtia patients underwent auricular reconstruction using 6th-8th costal cartilage. Thoracic computed tomography (CT) with three-dimensional reconstruction was performed preoperatively and during follow-up. Comparison of the hemithorax on the operated and unoperated sides was performed by measuring several thoracic parameters using Mimics software (Materialise, Belgium). The data were further analyzed by a paired-samples t-test. RESULTS: In the operated hemithorax, the costochondral junction midpoints moved medially (6th-8th), posteriorly (6th-7th) and descended less (6th-9th) with significant differences as P < 0.05 compared to the unoperated hemithorax. In addition, height differences indicated local depressions in the chest wall in the areas of cartilage defects (6th-9th, P < 0.05). Following local depression of the chest wall and migration of the ribs, the operated hemithorax also had a smaller area than the unoperated hemithorax (6th-9th, P < 0.05). The differences in the hemithorax were more significant in the midterm group (5-10 y) than in the other follow-up groups, while most parameters showed no significant differences in the long-term group (10-15 y). No significant differences were found in the modified Haller index. CONCLUSION: Multiple costal cartilage harvests caused morphological changes and asymmetry of the thorax in adolescent patients. As indicated by thoracic CT, significant changes occurred in the local area of cartilage defects, which did not affect the overall thorax. In the long term, more than 10 years after harvesting, the differences in the hemithorax between the operated and unoperated sides decreased significantly. This study provides an important reference for thoracic changes when applying auricular reconstruction in the pediatric microtia patients.

Clinical Observations of a Surgical Method Comprising a Combination of Cross Flap and Autologous Auricular Cartilage Transplantation in the Treatment of Type I to III Congenital Concha-Type Microtia.

OBJECTIVES: The present study attempted to investigate the clinical efficacy of a surgical method involving a combination of cross flap with autologous auricular cartilage transplantation in the treatment of type I to III congenital concha-type microtia. METHODS: The present retrospective study was conducted on the clinical and postoperative data of 50 patients with unilateral type I to III concha-type microtia treated with a combination of cross flap and autologous auricular cartilage transplantation at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2018 to December 2021. RESULTS: The postoperative perimeters of malformed ears were significantly larger than the preoperative perimeters (P < .05). Of the total, 2 patients exhibited incision dehiscence, 3 patients exhibited incision infection, 2 patients exhibited flap hematoma, and 1 patient exhibited ischemic necrosis at the flap tip. The satisfaction rate of the patients and their families was 100%. CONCLUSIONS: The surgical method involving a combination of cross flap and autogenous auricular cartilage transplantation was effective in treating patients with type I to III congenital concha-type microtia, and therefore, this surgical approach can be applied widely to correct this deformity.

Evaluation of respiratory system anomalies associated with microtia in a Chinese specialty clinic population.

BACKGROUND: Microtia is a congenital malformation of the external ear often with one or more associated congenital anomalies. The purpose of this study was to identify the characteristics and prevalence of respiratory anomalies in patients with microtia, and clarify the importance of this association in the perioperative period of patients' external ear reconstruction surgery. METHODS: Data were collected from 923 microtia patients between August 2017 and December 2020 in the Department of Auricular Reconstruction at the Plastic Surgery Hospital of Peking Union Medical College. Co-occurring respiratory anomalies were detected using chest computed tomography plus three-dimensional reconstruction and Chest X-ray. Physical examination was performed to assess the severity and type of microtia by trained clinicians. Fisher's exact test was used to analyze the relation between laterality of pulmonary underdevelopment and microtia type. RESULTS: Among the 923 participants enrolled in the study, we identified 21 cases (2.3%) having respiratory system anomalies, consisting of 6 cases with pulmonary underdevelopment (28.6% of all anomalies of respiratory system detected), 2 cases with tracheal bronchus (9.5%), 1 case with tracheal diverticula (4.8%), 11 cases with lung bullae(52.4%), and 1 case with pulmonary azygos lobe (4.8%). The laterality of pulmonary underdevelopment was related to the type of microtia (difference between types, p < 0.05), as patients with concha-type remnant ear had pulmonary underdevelopment ipsilaterally. CONCLUSIONS: This study represents the first detailed and thematic study of a association featured by microtia and respiratory anomalies. Characteristics and prevalence of respiratory anomalies was observed in a Chinese clinical microtia population. Early diagnosis of associated respiratory malformations had practical clinical significance for microtia patients, plastic surgeons and anesthesiologists. Future studies are required to improve understanding of this association and its cause.

Identification of a novel CYP26A1 mutation in a Chinese family with congenital microtia.

OBJECTIVES: Microtia is defined as a congenital malformation characterized by a small, abnormally shaped auricle, with atresia or stenosis of the auditory canal. This study investigated a mutation of the cytochrome P450, family 26, subfamily A, polypeptide 1(CYP26A1) gene, which is considered important in craniofacial development, in a family affected with microtia. METHODS: Whole-exome sequencing (WES) was performed on the proband and his family members to identify disease-associated variants. Computational predictions of the altered protein were analyzed using several bioinformatics tools. The wild-type (WT) and mutant forms of CYP26A1 cDNA were transfected into human embryonic kidney cells, and the mRNA and protein levels were compared using quantitative polymerase chain reaction (qPCR) and Western blot analyses. RESULTS: In this two-generation family, the proband and his mother were diagnosed with unilateral microtia. Unilateral microtia and ipsilateral accessory ear were observed in one of the twins, who were sisters of the proband. The father and the other twin showed no abnormal clinical features. A heterozygous mutation of a C to T in the CYP26A1 gene, which leads to truncation of the CYP26A1 protein, was identified in this family. The nonsense mutation cosegregated with patients and was absent in normal members of the family. The prediction software indicated that it was a possibly pathogenic mutation. The structure of the protein varied significantly between the WT and mutant proteins. Functional analysis showed that this mutation caused a significant decrease in both the mRNA and protein levels. CONCLUSIONS: Our findings suggest that this mutation of CYP26A1 may be a pathogenic factor leading to the phenotypes of microtia and accessory ear in this family. Further studies are needed to prove the function of this mutation and to explore the possible mechanism by which this variant is involved in the occurrence of microtia.

Diagnostic accuracy of imaging modalities in differentiating xanthogranulomatous cholecystitis from gallbladder cancer.

BACKGROUND: The aim of this study was to assess the diagnostic performance of radiological imaging in differentiating xanthogranulomatous cholecystitis (XGC) from gallbladder cancer (GBC). METHODS: A retrospective analysis of the radiological imaging performed in patients who had pathologically confirmed XGC or GBC between December 2004 to April 2016 was performed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality, and combined imaging modalities were calculated. RESULTS: A total of 218 patients (XGC =109, GBC =109) were identified; 19 patients received all of abdominal ultrasound (US), contrast-enhanced ultrasound (CEUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT); 21 received four of these imaging examination types; 45 received three examinations; 58 received two examinations; and 75 received only one examination. The sensitivity and specificity of CEUS was 90% and 93%, respectively, higher than abdominal US (80%, 86%), CT (71%, 92%), MRI (75%, 90%), and PET/CT (55%, 90%) (all values respective). The sensitivity, specificity, NPV, and PPV of the US combined with CEUS were 91%, 90%, 94%, and 85%, respectively. Although the specificity of CEUS + CT and CEUS + MRI were 100% and 92%, respectively, the sensitivity of CEUS + CT and CEUS + MRI were both only 67%. CONCLUSIONS: The Abdominal US is not sufficiently accurate to confidently guide clinical practice, and CEUS showed better diagnostic performance than the other imaging modalities in differentiating XGC from GBC. The combination of abdominal CEUS and CT is helpful for differential diagnosis, as it indicates GBC with better specificity and PPV.