Epidemiological Study of Neonatal Congenital Microtia in Shandong Province, China, 2011-2020.

OBJECTIVE: Congenital microtia is a common congenital disease in newborns. The specific cause of congenital microtia is currently unknown. The main objective of this study is to elucidate the epidemiological characteristics of congenital microtia and explore the possible etiology of congenital microtia. METHODS: Part of the newborn data from 2011 to 2020 in Shandong Province Birth Defects Monitoring Hospitals were randomly selected. The software GraphPad Prism 9 was used to analyze the data and draw figures. RESULTS: A total of 4247 infants were diagnosed with congenital malformation among 149,525 newborns randomly selected from the Shandong Province Birth Defects Monitoring Hospitals. Among them, a total of 115 infants were diagnosed with congenital microtia. The mean incidence of microtia during 10 years was 76.14±21.93 per 100,000 infants. The mean incidence of microtia in infants with congenital malformation was 2.67±0.75%. The average incidence of male and female infants with microtia during 10 years were 86.93±23.22 and 64.18±32.71 per 100,000 infants, respectively. In terms of maternal age, the older the mother, the higher the incidence of microtia. In terms of the place of residence, rural infants have a higher incidence of microtia than urban infants. CONCLUSIONS: The average incidence of microtia was 76.14±21.93 per 100,000 infants in Shandong Province, China, 2011-2020. The female-to-male incidence ratio was 1.45:1. The authors recommend that women choose to give birth at the age of 25 to 29. They hope that the government will take measures to improve the medical and health conditions in rural areas and improve parenting knowledge in rural areas. This can effectively reduce the prevalence of microtia in infants.

Duplications involving the long range HMX1 enhancer are associated with human isolated bilateral concha-type microtia.

BACKGROUND: Microtia is a congenital anomaly of ear that ranges in severity from mild structural abnormalities to complete absence of the outer ears. Concha-type microtia is considered to be a mild form. The H6 family homeobox 1 transcription factor gene (HMX1) plays an important role in craniofacial structures development. Copy number variations (CNVs) of a downstream evolutionarily conserved enhancer region (ECR) of Hmx1 associated with ear and eye abnormalities have been reported in different animals, but not yet in human. To date, no genetic defects responsible for isolated human microtia has been reported except for mutations in HOXA2. Here we recruited five Chinese families with isolated bilateral concha-type microtia, and attempt to identify the underlying genetic causes. METHODS: Single Nucleotide polymorphism (SNP) array was performed to map the disease locus and detect CNVs on a genome scale primarily in the largest family (F1). Whole genome sequencing was performed to screen all SNVs and CNVs in the candidate disease locus. Array comparative genomic hybridization (aCGH) was then performed to detect CNVs in the other four families, F2-F5. Quantitative real-time polymerase chain reaction (qPCR) was used to validate and determine the extent of identified CNVs containing HMX1-ECR region. Precise breakpoints in F1 and F2 were identified by gap-PCR and sanger sequencing. Dual-luciferase assays were used to detect the enhancer function. qPCR assays were also used to detect HMX1-ECR CNVs in 61 patients with other types mictrotia. RESULTS: Linkage and haplotype analysis in F1 mapped the disease locus to a 1.9 Mb interval on 4p16.1 containing HMX1 and its downstream ECR region. Whole genome sequencing detected no potential pathogenic SNVs in coding regions of HMX1 or other genes within the candidate disease locus, but it detected a 94.6 Kb duplication in an intergenic region between HMX1 and CPZ. aCGH and qPCRs also revealed co-segregated duplications in intergenic region downstream of HMX1 in the other four families. The 21.8 Kb minimal overlapping region encompassing the core sequences consensus with mouse ECR of Hmx1. Luciferase assays confirmed the enhancer function in human sequences, and proved that HOXA2 could increase its enhancer activity. No CNVs were detected in HMX1-ECR regions in 61 patients with other type of microtia. CONCLUSION: Duplications involving long range HMX1 enhancers are associated with human isolated bilateral concha-type microtia. We add to evidences in human that copy number variations in HMX1-ECR associates with ear malformations, as in other species. This study also provides an additional example of functional conserved non-coding elements (CNEs) in humans.

A Novel Method for Making an Auricle Framework Like Lego Building Blocks.

OBJECTIVES: The traditional Tanzer-Brent method, which uses the integral engraving of costal cartilage, provides insufficient three-dimensional sensation and is characterized by poor firmness of the auricle framework. This tends to cause the absorption deformation of the auricle framework after surgery. In order to reduce the absorption deformation as well as make the reconstructed auricle more three-dimensional and the ear shape more realistic, our ear reconstruction team invented a novel method to make an auricle framework with autologous costal cartilage. The auricle framework made by this novel method has been applied to auricle reconstruction and has achieved excellent surgical results. PATIENTS AND METHODS: Clinical data and postoperative data were collected for patients with unilateral microtia who received auricle reconstruction using the novel method of auricle framework construction in Plastic Surgery Hospital from January 2020 to June 2022. The therapeutic effect of this novel method was evaluated by the satisfaction rate of patients and their families and by the prevalence of postoperative complications. RESULTS: A total of 60 patients were enrolled in this study. The average age was (10.95 ± 2.97) years old. The mean follow-up time was 24.02 ± 1.52 months. The satisfaction rate of patients and their families was 96.7%. In terms of postoperative complications, two patients had postoperative infection, one patient had framework exposure, no patients had framework absorption and deformation, two patients had postoperative hematoma, and three patients had scar hyperplasia. CONCLUSION: This novel method of making the auricle framework is more standardized, easier to master for plastic surgeons, and more conducive to the clinical application of plastic surgery. Through this study, we believe that this novel method offers significant therapeutic advantages and can be used as a unified standard for construction of an auricle framework using autologous costal cartilage.