Long-pulsed neodymium-doped yttrium aluminum garnet for hair reduction in pediatric microtia repair.

Microtia is the term for congenital malformation of the ear in which the external and internal ear are absent or malformed. Surgical reconstruction is a common management approach and occasionally requires hair reduction of the newly constructed auricle. Few studies have investigated lasers for this purpose. We conducted a retrospective chart review of patients seen at a single institution between 2012 and 2021 who underwent laser hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet laser (Nd:YAG). Efficacy ratings were done through review of clinical photographs. Twelve patients were identified with 14 total ears treated. The number of laser treatments varied from 1 to 9 sessions with an average of 5.1 treatments. The majority (8/12) had an "excellent" or "very good" response, one patient had a "good" response, and three were lost to follow-up. Other than pain, there were no side effects documented. Nd:YAG laser was both effective and safe in our pediatric cohort, without any cutaneous side effects in patients with darker skin.

Desentrañando la sinfonía genética y epigenética: una revisión narrativa sobre la interacción en la etiología de la microtia / Unravelling the genetic and epigenetic symphony: a narrative review exploring the interplay in etiology of microtia

La microtia, una anomalía congénita del oído externo, sirve como modelo para explorar la compleja sinergia entre la genética y la epigenética en la determinación de resultados fenotípicos. La genética, que reside en el ADN, proporciona el plano para el desarrollo, mientras que las modificaciones epigenéticas modulan la expresión génica sin alterar la secuencia del ADN. Esta revisión exhaustiva se adentra en su influencia combinada sobre la etiología de la microtia, desentrañando la importancia de la metilación del ADN, las modificaciones de las histonas y los microARNs en la formación del oído y su susceptibilidad a las señales ambientales. Las investigaciones genéticas incluyen análisis de pedigrí y secuenciación del exoma completo, destacando genes esenciales como HOXA4 y CHST15. Las asociaciones sindrómicas subrayan la base genética multifacética de la microtia. Esta interacción dinámica entre la genética y la epigenética enriquece nuestro entendimiento de las anomalías del desarrollo, ofreciendo perspectivas para intervenciones a medida y estrategias clínicas para manejar esta condición de manera personalizada. La continua exploración de estas interacciones abre caminos para descifrar procesos de desarrollo complejos y expandir nuestra comprensión de anomalías relacionadas. (AU)

Microtia, a congenital anomaly of the external ear, serves as a model to explore the intricate synergy between genetics and epigenetics in shaping phenotypic outcomes. Genetics, residing in DNA, provides the blueprint for development, while epigenetic modifications modulate gene expression without altering the DNA sequence. This comprehensive review delves into their combined influence on microtia’s etiology, unravelling the significance of DNA methylation, histone modifications, and microRNAs in ear formation and their susceptibility to environmental cues. Genetic investigations encompass pedigree analysis and whole-exome sequencing, spotlighting pivotal genes like HOXA4 and CHST15. Syndromic associations underscore the multifaceted genetic underpinning of microtia. This dynamic interplay between genetics and epigenetics enriches our understanding of developmental anomalies, offering insights for tailored interventions and clinical strategies to manage this condition in a personalized manner. The continuous exploration of these interactions opens avenues for deciphering intricate developmental processes and expanding our comprehension of related anomalies. (AU)

Protein profile of ear auricle cartilage and the important role of ITGB1/PTK2 in microtia.

BACKGROUND: Microtia is a congenital malformation of the external ear that involves anything from a small reduction in size to a complete absence. The external ear is composed of elastic cartilage which is also the important skeleton of the outer ear. However no previous study explored the difference between abnormal elastic cartilage and normal cartilage in the molecular level. METHODS: Microtia cartilage and normal cartilage tissue samples from patients subjected to autologous costal cartilage reconstruction were obtained in surgery. Total proteins were extracted and purified, and then proteomic analyzed via LC-MS/MS using DDA/DIA data collection methods. Proteins were also isolated with lysis beads and then analyzed via antibody chip. Differentially expressed proteins were identified in both experiments and further analyzed with functional enrichment analysis and KEGG pathway analysis. Valuable regulatory gene expression level was verified by RT-PCR. RESULTS: A total of 4178 protein types were identified in the DDA experiment. A total of 2154 proteins were quantified, 172 of which were significantly upregulated and 82 downregulated in the microtia group (P < 0.05). Antibody chip detection allowed identification of 584 protein phosphorylation sites with 102 upregulation sites and 9 downregulation sites (P < 0.05). Differentially altered proteins were annotated to 143 KEGG pathways, while differentiated phosphate site-associated genes were annotated into 21 KEGG pathways. Two intersecting pathways, the PI3K/AKT/mTOR pathway and the focal adhesion pathway, may paly important role on ear auricle cartilage development. One item is significant in both differential protein expression and phosphorylation. Integrin beta-1, that is downregulated in protein quantification of the microtia group. The mean ITGB1 mRNA level of the microtia patient group was significantly lower than in the healthy control group (P = 0.0007 < 0.05). And the gene expression of downstream gene PTK2 was also decreased. (P = 0.0288 < 0.05). CONCLUSION: The research locates the key protein Integrin Beta-1, and verified it at the mRNA level. The increasing level of ITGB1 and decreasing of PTK2 may play an important role in congenital ear deformity. This research will inspire more otolaryngologists and orthopedics doctors to pay attention to the etiology and mechanism of microtia.

Maternal risk factors for severe microtia/atresia in China: A case-control study.

OBJECTIVE: Microtia/atresia is a severe malformation of the external ear. Previous studies have reported the potential risk factors on microtia, whereas few focused on severe microtia/atresia. The aim of the study was to investigate the effects of maternal exposure to environmental risk factors in patients with severe microtia/atresia in China. METHODS: A case-control study was conducted. Cases were patients with severe microtia/atresia who presented to PUMCH between January 2014 and October 2017. A total of 322 patients with severe microtia/atresia were enrolled and 322 normal controls matched 1:1 with the patients by sex, age and nationality were enrolled. The designed questionnaires were completed and data were gathered. Odds ratios were estimated with logistic regression models along with 95% confidence intervals in severe microtia/atresia. RESULTS: Most cases were males(68.6%), and the cases were observed more common in unilateral(80.7%), right-sided (54.0%). Multivariate logistic regression analysis showed that threatened abortion (OR 4.066,95% CI = 2.360-7.007), NSAIDs (OR 2.576,95% CI = 1.079-6.148), virus infection (OR 1.933,95% CI = 1.148-3.256), anemia (OR 1.902,95% CI = 1.026-3.526), miscarriages (OR 1.804,95% CI = 1.425-2.285), maternal age (OR 1.079,95% CI = 1.015-1.148) and paternal age (OR 1.061,95% CI = 1.003-1.122) were associated with a higher risk of severe microtia/atresia. CONCLUSION: These results support that some maternal risk factors could be associated with severe microtia/atresia.

Auricular Reconstruction in Hemifacial Microsomia with an Expanded Two-Flap Method.

BACKGROUND: Reconstruction of external ear is important for the child/adult with craniofacial deformities to achieve balance and harmony of the face and head. The aim of this study was to investigate the clinical application of an expanded two-flap method for auricular reconstruction in hemifacial microsomia. METHODS: Between January of 2014 and November of 2015, 111 hemifacial microsomia patients with microtia underwent auricular reconstruction with an expanded two-flap method. The clinical data of these patients were reviewed retrospectively. Thirty-two patients (28.8 percent) underwent auricular reconstruction in combination with simultaneous mandibular lengthening. Microtia was treated by an expanded two-flap method, which includes three stages. In the first stage, the retroauricular skin was expanded using a kidney-shaped tissue expander. In the second stage, the costal cartilage was harvested and the framework was fabricated. The anterior surface of the framework was enveloped by the expanded skin flap. The posterior surface and the helical rim of the framework is covered by a retroauricular fascial flap and a full-thickness skin graft. In the third stage, the tragus was reconstructed, the lobule was formed, and the concha was excavated. The surgical planning and skills of auricular reconstruction-especially for hemifacial microsomia-were described and analyzed. The median duration of follow-up was 8.3 months. RESULTS: There were nine cases (8.1 percent) of complications in our study. During follow-up, 103 patients (92.8 percent) had satisfactory outcomes, seven (6.3 percent) had partially satisfactory outcomes, and one patient (0.9 percent) had an unsatisfactory outcome. CONCLUSION: Auricular reconstruction using an expanded two-flap method in hemifacial microsomia is safe and effective, with satisfying middle-term results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non-syndromic microtia and distinctive ear morphology.

Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five-generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non-syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development.

Maternal occupational exposure to ionizing radiation and major structural birth defects.

BACKGROUND: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects. METHODS: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects. RESULTS: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy. CONCLUSION: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies.