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.

[Contemporary diagnosis and management of congenital microtia and aural atresia : Part 2: Overview of therapeutic approaches]. / Aktuelle Diagnostik und Therapie bei Ohrmuscheldysplasien und Gehörgangsfehlbildungen : Teil 2: Übersicht der verschiedenen Therapieansätze.

Congenital malformations of the pinna and aural atresia can result in major aesthetic and functional deficits. Knowledge about embryologic developments and established classification systems is an essential requirement when dealing with affected patients. Early detection of deficiencies and introduction of appropriate diagnostic measures is vital to initiate adequate therapies and prevent long-term disabilities. Treatment for malformations of the pinna-if requested-is mostly surgical, infrequently an epithesis is applied. As in other surgical fields, tissue engineering will likely play a crucial role in the future. Treatment of aural stenosis and atresia aims at improvement of hearing levels and prevention of secondary complications like cholesteatoma and chronic otorrhea. Auditory rehabilitation comprises a spectrum from conventional hearing aids to invasive hearing implants, the latter being favored in recent years.

[Contemporary diagnosis and management of congenital microtia and aural atresia : Part 1: Principles and diagnosis]. / Aktuelle Diagnostik und Therapie bei Ohrmuscheldysplasien und Gehörgangsfehlbildungen : Teil 1: Grundlagen und Diagnostik.

Congenital malformations of the pinna and aural atresia can result in major aesthetic and functional deficits. Knowledge about embryologic developments and established classification systems is an essential requirement when dealing with affected patients. Early detection of deficiencies and introduction of appropriate diagnostic measures is vital to initiate adequate therapies and prevent long-term disabilities. Treatment for malformations of the pinna-if requested-is mostly surgical, infrequently an epithesis is applied. As in other surgical fields, tissue engineering will likely play a crucial role in the future. Treatment of aural stenosis and atresia aims at improvement of hearing levels and prevention of secondary complications like cholesteatoma and chronic otorrhea. Auditory rehabilitation comprises a spectrum from conventional hearing aids to invasive hearing implants, the latter being favored in recent years.

Evaluating International Diagnostic, Screening, and Monitoring Practices for Craniofacial Microsomia and Microtia: A Survey Study.

To (1) appraise current international classification and clinical management strategies for craniofacial microsomia (CFM) and microtia, and (2) to assess agreement with the European Reference Network "European Guideline Craniofacial Microsomia" recommendations on screening and monitoring.This was a cross-sectional online survey study. The survey consisted of 44 questions on demographics, diagnostics and classification, obstructive sleep apnea, feeding difficulties, speech and language development, hearing, ocular abnormalities, visual development, orthodontic screening, genetic counselling, psychological wellbeing, and extracraniofacial anomalies.Respondents were participants of 3 international cleft and craniofacial conferences, members of the American Cleft Palate and Craniofacial Association and members of the International Society for Auricular Reconstruction. Respondents were requested to complete 1 questionnaire per multidisciplinary team.Fifty-seven responses were received from 30 countries (response rate ∼3%).The International Consortium for Health Outcomes Measurement diagnostic criteria were used by 86% of respondents, though 65% considered isolated microtia a mild form of CFM. The Orbit, Mandible, Ear, Facial Nerve and Soft Tissue classification system was used by 74% of respondents. Agreement with standardized screening and monitoring recommendations was between 61% and 97%. A majority of respondents agreed with screening for extracraniofacial anomalies (63%-68%) and with genetic counselling (81%).This survey did not reveal consistent agreement on the diagnostic criteria for CFM. Respondents mostly supported management recommendations, but frequently disagreed with the standardization of care. Future studies could focus on working towards international consensus on diagnostic criteria, and exploring internationally feasible management strategies.

Meier-Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test.

Meier−Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, the absence of or hypoplastic patellae and other skeletal anomalies. Skeletal symptoms overlapping with other syndromes make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay indicated that variant c.449+5G>A causes complete skipping of exon 4 in the ORC6 gene. The parents requested urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Our results may help prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS etiology and improve the quality of genetic counselling for affected families.

The Course of Superficial Temporal Artery in Patients with Microtia and its Relationship with the Remnant.

OBJECTIVE: Temporoparietal fascia is important for auricular reconstruction or repair after auricular reconstruction. Thus, the course of the superficial temporal artery (STA) is of vital importance to prevent destruction of the artery. The purpose of this study was to evaluate the course of the superficial temporal artery in patients with congenital microtia and its relationship with remnants. METHODS: This was a prospective study. Patients with microtia who underwent auricular reconstruction in our hospital from January 2021 to July 2021 underwent ultrasound examination of the STA. Under the guidance of ultrasound, the superficial temporal artery and its branches were located and marked on the body surface before the operation, ranging from the zygomatic arch plane to the temporal parietal artery. In addition, the hemodynamics of the STAs were recorded. RESULTS: A total of 108 patients with microtia were collected, including 106 patients with unilateral microtia and 2 patients with bilateral microtia. There were 82 cases of lobule type, 21 cases of small concha type, and 7 cases of large concha type. The superficial temporal artery in 103 ears was divided into two branches: the parietal branch and the frontal branch, but there was only one branch in 7 ears. The parietal branch was absent in 5 cases, and the frontal branch was absent in 2 cases. In most of the ears, the bifurcation was located above the zygomatic arch plane. Only in 2 ears was the bifurcation located below the zygomatic arch, and the most common bifurcation position was the eyebrow arch level (43.7%). Regarding the shortest distances between the STA and the remnant, they were less than 0.5 cm in 47 ears, more than 1 cm in 30 ears, and 0.5 cm to 1 cm in 33 ears. CONCLUSION: The course of STA varied greatly and there were occasional single branches. The distances between the STA and remnant were often near 0.5 cm by ultrasonography. Therefore, when removing the remnant and separating the pocket, care should be taken to avoid arterial injury. 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 .

A mutation of EYA1 gene in a Chinese Han family with Branchio-Oto syndrome.

ABSTRACT: Branchio-Oto (BO) syndrome is one of the common syndromic forms of hearing loss. In this study, we aimed to characterize the clinical and genetic features of BO syndrome in a Chinese deaf family.The proposita in this study was a 29-years-old Chinese female with hearing loss, microtia, anterior concave auricle, and right branchial fistula. The family members agreed to undergo clinical examination. We collected blood samples from 7 family members, including 4 affected by the syndrome. Genomic DNA was extracted and subjected to Sanger sequencing. In addition, bioinformatics software SWISS MODEL was used to predict the protein encoded by EYA transcriptional coactivator and phosphatase 1 (EYA1) gene.Intra-familial consistency can be observed in the clinical phenotypes of BO syndrome in this family. EYA1 c.1627C>T (p.Gln543Ter) mutation was identified as the pathogenic cause in this family.This study reports a mutation associated with BO syndrome in a Chinese Han family. We highlight the utility of genetic testing in the diagnosis of BO syndrome. Thus, we believe that this report would provide a basis for the diagnosis of similar diseases in the future.

MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency.

The MCM2-7 helicase is a heterohexameric complex with essential roles as part of both the pre-replication and pre-initiation complexes in the early stages of DNA replication. Meier-Gorlin syndrome, a rare primordial dwarfism, is strongly associated with disruption to the pre-replication complex, including a single case described with variants in MCM5. Conversely, a biallelic pathogenic variant in MCM4 underlies immune deficiency with growth retardation, features also seen in individuals with pathogenic variants in other pre-initiation complex encoding genes such as GINS1, MCM10, and POLE. Through exome and chromium genome sequencing, supported by functional studies, we identify biallelic pathogenic variants in MCM7 and a strong candidate biallelic pathogenic variant in MCM3. We confirm variants in MCM7 are deleterious and through interfering with MCM complex formation, impact efficiency of S phase progression. The associated phenotypes are striking; one patient has typical Meier-Gorlin syndrome, whereas the second case has a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. We provide further insight into the developmental complexity of disrupted MCM function, highlighted by two patients with a similar variant profile in MCM7 but disparate clinical features. Our results build on other genetic findings linked to disruption of the pre-replication and pre-initiation complexes, and the replisome, and expand the complex clinical genetics landscape emerging due to disruption of DNA replication.

Resultado quirúrgico y calidad de vida en reconstrucción auricular autóloga. Hospital General Dr. Manuel Gea González. México / Surgical outcomes and quality in autologous auricle reconstruction. Hospital General Dr. Manuel Gea González. México

INTRODUCCIÓN Y OBJETIVO: La microtia es un problema estético que conlleva una afección psicosocial en el desarrollo del paciente. La reconstrucción auricular mediante injerto costal autólogo es el procedimiento más usado. Determinamos los resultados quirúrgicos en nuestro hospital y el impacto en la calidad de vida de los pacientes con microtia sometidos a reconstrucción auricular con cartílago costal autólogo. MATERIAL Y MÉTODO: Estudio observacional, descriptivo, transversal y prolectivo en pacientes con diagnóstico de microtia uni o bilateral 1 año después de la reconstrucción. Evaluamos el resultado quirúrgico mediante cuestionario desarrollado y publicado por la primera autora, calificando características de apariencia estética de la oreja. Evaluamos la calidad de vida del paciente mediante cuestionario Glasgow Benefit Inventory, versión validada al español, en mayores de 15 años; para pacientes pediátricos utilizamos cuestionario Glasgow's Children's Benefit Inventory, versión traducida y validada por traductor especializado. RESULTADOS: Recogimos 83 pacientes con edad de 8 a 46 años. En la evaluación quirúrgica 13 pacientes (15.6%) tuvieron un resultado excelente, 27 (32.5%) bueno, 29 (34.9%) regular y 14 malo (16.8%). En la evaluación de calidad de vida encontramos en la escala total puntuación positiva en 78 pacientes (93.9%) y negativa en 5 (6%). CONCLUSIONES: El estudio presenta un panorama objetivo de las expectativas del cirujano sobre satisfacción y bienestar del paciente. Si bien solo encontramos resultados buenos y excelentes en el 48%, al revisar la escala de satisfacción encontramos puntaciones positivas, con bienestar en casi el 94%. Es importante que los pacientes conozcan nuestra preocupación por saber el impacto de la intervención y que podamos retroalimentar nuestra práctica quirúrgica. Hasta donde sabemos, este es el primer estudio en México que evalúa ambos aspectos

BACKGROUND AND OBJECTIVE: Microtia is not only an aesthetic problem but involves patient psychosocial development. The gold standard for auricular reconstruction is autologous costal cartilage. Our aim is to evaluate surgical outcomes and impact in quality of life after auricular reconstruction with autologous costal cartilage in microtia patients at our hospital. METHODS: Observational, descriptive, cross an prolective study on patients with uni or bilateral microtia 1 year after auricular reconstruction procedure. Surgical outcome was evaluated with a method previously published by the first author evaluating auricular aesthetic characteristics. Quality of life was evaluated with Glasgow Benefit Inventory, validated in Spanish, for over 15 years old patients; for pediatric patients we used the Glasgow's Children's Benefit Inventory, in a validated translated version. RESULTS: The study group was composed by 83 patients from 8 to 46 years old. Surgical outcome were excellent in 13 cases (15.6%), good in 27 (32.5%), regular in 29 cases (34.9%) and bad in 14 (16.8%). Quality of life had a positive total score in 78 cases (93.9%) and negative in 5 (6%). CONCLUSIONS: The study allows us an objective overview of surgeon's expectations regarding patient satisfaction and well-being. Although we only found good and excellent results in 48% of the patients, when reviewing the satisfaction scale we found positive scores in almost 94%. It`s important that patients know our concern about the impact of our intervention and to provide feedback on our surgical practice. As far as we know, this is the first study in Mexico evaluating both aspects

Comentario al artículo "Resultado quirúrgico y calidad de vida en reconstrucción auricular autóloga. Hospital General Dr. Manuel Gea González. México" / No disponible

No disponible

Respuesta al comentario de la Dra. F. Valotta / No disponible

No disponible

High-resolution computed tomography evaluation of congenital aural atresia - how useful is this?

OBJECTIVE: To depict various temporal bone abnormalities on high-resolution computed tomography in congenital aural atresia patients, and correlate these findings with auditory function test results and microtia subgroup. METHODS: Forty patients (56 ears) with congenital malformation of the auricle and/or external auditory canal were evaluated. Auricles were graded according to Marx's classification, divided into subgroups of minor (grades I and II) and major (III and IV) microtia. Other associated anomalies of the external auditory canal, tympanic cavity, ossicular status, oval and round windows, facial nerve, and inner ear were evaluated. RESULTS: Minor and major microtia were observed in 53.6 and 46.4 per cent of ears respectively. Mean hearing levels were 62.47 and 62.37 dB respectively (p = 0.98). The malleus was the most commonly dysplastic ossicle (73.3 vs 80.8 per cent of ears respectively, p = 0.53). Facial nerve (mastoid segment) abnormalities were associated (p = 0.04) with microtia subgroup (80 vs 100 per cent in minor vs major subgroups). CONCLUSION: Microtia grade was not significantly associated with mean hearing levels or other ear malformations, except for external auditory canal and facial nerve (mastoid segment) anomalies. High-resolution computed tomography is essential in congenital aural atresia, before management strategy is decided.

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.

Validity and reliability of three-dimensional costal cartilage imaging for donor-site assessment and clinical application in microtia reconstruction patients: A prospective study of 22 cases.

OBJECTIVES: This study assesses the ability to reconstruct costal cartilage images by using three-dimensional visualisation software (Mimics) based on semi-automated segmentation algorithm and to investigate its reliability and validity with an anthropometric analysis. DESIGN: Observational prospective study. SETTING: Plastic surgery department of a tertiary hospital. PARTICIPANTS: Twenty-two microtia patients who underwent autologous ear reconstruction. MAIN OUTCOME MEASURES: Preoperative thoracic computed tomography data were processed to Mimics software for three-dimensional costal cartilage imaging. The length, width, thickness and volume of the 9th costal cartilages were calculated from these images and compared with the direct measurements (DM) obtained intraoperatively. RESULTS: The intra-examiner reliability and inter-examiner reliability were high in terms of all four measurements (intraclass correlation coefficients, ICC: 0.876-0.984). There were no significant differences between image-based anthropometry and DM in the linear measurements except for the volume (P < .05). The mean volume calculation error of Mimics was -0.08 ± 0.13 mL. No correlation was found between the anthropometric variables and the absolute errors (P > .05). Furthermore, Bland-Altman plots were used to evaluate the agreement between the two methods. CONCLUSIONS: Despite a very small error was found in volume calculation, Mimics software was accurate and reliable in linear calculation. Three-dimensional costal cartilage imaging was found to be an efficient tool for morphological evaluation of costal cartilages. We believe that with the application of individualised cartilage models based on three-dimensional printing, the use of customised ear framework carving will be practicable in surgical training.

[Case report of familial microtia combined with tetralogy of Fallot and scoliosis and literature review].

Summary Microtia is a kind of malformation affecting the development of the external ear and middle ear. In China, researches have pointed out that the incidence of microtia was 3.06 per 10 000 people. About 40% of patients with microtia were identified with other systemic malformation, and the commom complications included congenital heart disease, scoliosis, anophthalmia, cleft palate, facial asymmetry, facial asymmetry, etc. Of which, the prevalence of microtia with congenital heart disease was 18.5%, and it was 7% of patients with scoliosis. It is very rare for patients of microtia combined with multi-malformations. In this study, we reported a case of familial microtia combined with tetralogy of Fallot and scoliosis, and undertook a systematic review of the literature.

Auricular reconstruction.

External ear abnormalities are common. These may affect ear shape, size, prominence and degree of development. They may also be associated with hearing loss. The early identification and management of hearing loss is essential. There are several options for reconstruction of the external ear using both autologous and non-autologous techniques. The aim of this article is to outline the different reconstructive options.