Linguistic network in early deaf individuals: A neuroimaging meta-analysis.

This meta-analysis summarizes evidence from 44 neuroimaging experiments and characterizes the general linguistic network in early deaf individuals. Meta-analytic comparisons with hearing individuals found that a specific set of regions (in particular the left inferior frontal gyrus and posterior middle temporal gyrus) participates in supramodal language processing. In addition to previously described modality-specific differences, the present study showed that the left calcarine gyrus and the right caudate were additionally recruited in deaf compared with hearing individuals. In addition, this study showed that the bilateral posterior superior temporal gyrus is shaped by cross-modal plasticity, whereas the left frontotemporal areas are shaped by early language experience. Although an overall left-lateralized pattern for language processing was observed in the early deaf individuals, regional lateralization was altered in the inferior temporal gyrus and anterior temporal lobe. These findings indicate that the core language network functions in a modality-independent manner, and provide a foundation for determining the contributions of sensory and linguistic experiences in shaping the neural bases of language processing.

Simulator Verification Is Potentially Beneficial for the Fitting of Softband Bone Conduction Hearing Devices in Young Children.

HYPOTHESIS: The current study employed a skull-simulator verification method to assess whether the output of softband bone conduction hearing devices (BCHDs) at the manufacturer's default settings deviated widely from the target determined by the fitting formula. BACKGROUND: Real ear analysis is utilized for the verification of the fitting of air conduction hearing devices (ACHDs) in a variety of institutions. This procedure, however, has not been used in the fitting of BCHDs, largely due to the difficulty of testing the output of these devices to temporal bones. Despite the availability of skull simulators, they have not been utilized clinically to measure BCHD output. MATERIALS AND METHODS: This prospective, single-center study enrolled 42 subjects, aged 3 months to 10 years, with microtia-atresia-associated mild-to-severe bilateral conductive hearing loss. Hearing sensitivity was evaluated behaviorally by pure tone audiometry (PTA) in 22 subjects 4 years or older (the PTA group), and by auditory brainstem response (ABR) in 20 subjects younger than 4 years (the ABR group). Following 6 months of subjects wearing the prescribed softband BCHDs, their dial level (DL) thresholds were reassessed while using their own BCHDs, configured with zero gain across all frequencies, functioning solely as a bone vibrator. These DL thresholds were inputted into the fitting formula, desired sensation level-bone conduction devices (DSL-BCD) for children, to obtain the target values of BCHD output. The simulator output of the BCHD programmed at the manufacturer's default setting was measured in response to speech presented at 55, 65, and 80 dB SPL, followed by gain adjustment based on the differences between the simulator output and the target. Aided speech intelligibility index (SII) was measured before and after the gain adjustment. RESULTS: The softband BCHDs at the manufacturer's settings generally had lower output than the prescribed target values. This difference was larger at low frequencies and low levels. Across the 12 points tested (four frequencies from 500 to 4000 Hz multiplied by three levels), 22 (52.3%) and 42 (100%) BCHDs had deviations of +7 and +5 dB, respectively, at one point or more. The gain adjustments reduced the deviation and improved the SII values at the two lower levels of speech presented. CONCLUSION: The simulator output of softband bone conduction hearing devices (BCHDs) with the manufacturer's settings may exhibit significant deviations from the formula. Objective output verification should be considered a beneficial step in BCHD fitting and is recommended when applicable.

Possible germline mosaicism in a pedigree with Treacher Collins syndrome: A case report and brief review.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder, typically inherited as an autosomal dominant condition. Here, we report on a family in which germline mosaicism for TCS was likely present. The proband was diagnosed with TCS based on the typical clinical features and a pathogenic variant TCOF1 (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents' peripheral blood DNA samples, suggesting a de novo mutation had occurred in the proband. However, a year later, the proband's mother became pregnant, and the amniotic fluid puncture revealed that the fetus carried the same mutation as the proband. Prenatal ultrasound also indicated a maxillofacial dysplasia with unilateral microtia. The mother then disclosed a previous birth history in which a baby had died of respiratory distress shortly after birth, displaying a TCS-like phenotype. Around the same time, the proband's father was diagnosed with mild bilateral conductive hearing loss. Based on array data, we concluded that the father may have had germline mosaicism for TCOF1 mutation. Our findings highlight the importance of considering germline mosaicism in sporadic de novo TCOF1 mutations when providing genetic consulting, and prenatal diagnosis is important when the proband's parents become pregnant again.

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.

Hearing outcomes following cochlear implantation with anatomic or default frequency mapping in postlingual deafness adults.

PURPOSE: The aim of this study was to compare the outcomes of different mapping procedures based on anatomic or default frequency distribution in postlingual deafness adults who underwent cochlear implantation (CI). METHODS: Forty-eight adults with postlingual deafness who underwent CI (MED-EL) from January 2021 to May 2022 in our hospital were prospectively recruited. The participants were randomly assigned to two groups (the anatomic group and the default group). Postoperative computerized tomography (CT) scans were evaluated with Otoplan® to determine the angular insertion depth (AID) and the specific locations of the intracochlear electrodes. Anatomic maps were imported into MAESTRO 9.0 software (MED-EL) for anatomy-based fitting for anatomic group, while default mapping program was set up for the default group. Hearing thresholds, Speech Recognition Scores (SRS), and subjects' auditory and musical abilities were evaluated 1 year after using the CI. Differences were determined in two groups using Stata statistical software, with significance defined as p < 0.05. RESULTS: SRS under noisy conditions was significantly greater for anatomic group than the default group (p = 0.02). Under quiet conditions, however, mean hearing thresholds (0.5, 1, 2, and 4 kHz) and SRS did not differ significantly between the two groups (p = 0.07). Modified questionnaires showed that auditory (p = 0.02) and musical (p = 0.01) quality were significantly better following the anatomic mapping than the default procedure. CONCLUSION: CI program based on the anatomic distribution may bring better SRS under noise conditions as well as better auditory and musical qualities than based on the default frequency distribution.

Co-Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management.

OBJECTIVES/HYPOTHESIS: The co-occurrence of sensorineural hearing loss (SNHL) and congenital heart disease (CHD) is a rare condition with complex etiologies. The purpose of this study is to assess the etiologies, clinical features, and outcomes of cochlear implant (CI) in this patient population. STUDY DESIGN: Case series and literature review. METHODS: Clinical data of children who were diagnosed with SNHL and CHD and received CIs at a tertiary hospital from 2016 to 2021 were retrospectively analyzed. A literature review was performed to identify patients with SNHL and CHD. FINDINGS: Of the 382 children who underwent cochlear implantation at our center, eight (2.1%) were diagnosed with SNHL and CHD. A literature review identified 1525 patients from 254 studies; the database therefore consisted of 1533 patients. The most common genetic etiologies of co-occurring SNHL and CHD were CHARGE syndrome (36.3%), Turner syndrome (8.4%), 22q11.2 deletion (3.0%), Noonan syndrome (2.9%), and Down syndrome (2.5%), whereas the most common non-genetic etiologies were congenital rubella syndrome (22.9%) and SNHL after early cardiac surgery (5.5%). Most of the patients presented with congenital, bilateral, severe-profound SNHL requiring early rehabilitation. Of the 126 children who received CIs at a median age of 2.5 years, half showed delayed speech development at last follow-up. CONCLUSIONS: Co-occurring SNHL and CHD is a rare condition with complex etiologies. Timely hearing intervention with long-term follow-up and proper timing of heart surgery is essential for these children. LEVEL OF EVIDENCE: 4, case series Laryngoscope, 134:400-409, 2024.

Psychosocial status of patients with unilateral and bilateral microtia before auricular reconstruction surgery.

OBJECTIVE: Microtia can profoundly influence health-related quality of life. The aim of this study was to investigate the psychosocial status of children and adolescents with unilateral and bilateral microtia before reconstruction surgery. METHODS: Eighty-six patients with microtia from Peking Union Medical College Hospital (54 with unilateral microtia and 32 with bilateral microtia) responded to structured interviews before reconstruction surgery. The 3 clinically validated questionnaires were the Piers-Harris Children's Self-concept Scale (PHCSS), the Social Anxiety Scale for Children (SASC), and the Children's Loneliness Scale (CLS). Scores from the PHCSS and SASC were compared with Chinese norms. The total scores of the unilateral and bilateral groups were compared for all three questionnaires. RESULTS: Males with unilateral and bilateral microtia had significantly different PHSCC scores than norms (both P < 0.05), and male patients overall had a total score that was 10.61 ± 2.20 points lower than female patients overall. Patients who were 7-9 years-old in the unilateral group and 10 to 13 years-old in the bilateral group had lower total PHSCC scores than norms of the same age (both P < 0.05). There was no significant difference between patients and norms in the 14-16 years-old group. The SASC scores of patients were significantly higher than the norms (P < 0.05). The CLS score was significantly lower in the unilateral group than in the bilateral group (50.17 ± 14.63 vs. 61.38 ± 13.24, P < 0.05), but these two groups did not significantly differ in PHCSS and SASC scores. CONCLUSION: Compared to Chinese norms, children with unilateral and bilateral microtia had lower self-concept, especially males and those who were 7-13 years-old. Patients with microtia also had increased social anxiety and loneliness. Patients with bilateral microtia were more likely to report loneliness than those with unilateral microtia.

Altered regional activity and connectivity of functional brain networks in congenital unilateral conductive hearing loss.

Neuroimaging studies have shown marked alterations in brain function after auditory deprivation, with these alterations mainly caused by sensorineural hearing loss. To date, however, little is known about the patterns of functional brain reorganization in conductive hearing loss (CHL). The effects of congenital unilateral CHL on human brain were assessed by resting-state functional magnetic resonance imaging in 24 patients with unilateral microtia (UM) and 25 healthy controls. Focal brain function and seed-based functional connectivity were analyzed to characterize spontaneous activity and network changes in UM. Patients with UM showed common alterations in focal brain activities in the left inferior temporal gyrus across different measurements, with these alterations significantly associated with the duration of hearing loss. Additionally, focal brain activities were decreased in the auditory system and increased in the visual system, with a disassociated pattern shown in the default-mode system. Using the left inferior temporal gyrus as the seed region, patients with UM showed lower connectivity with the default-mode system and right visual regions but higher connectivity with the left frontoparietal regions when compared with controls. These results indicate that congenital partial hearing deprivation, despite normal bone conduction hearing, can induce widespread reorganizations that continue into adolescence and adulthood.

[Selection and application in the approach of Bonebridge implantation for bilateral congenital malformation of external and middle ear: selection and application].

Objective:According to whether auricle reconstruction has been performed before the implantation of Bonebridge, the different surgical plan of combination of ear reconstruction and hearing rehabilitation with Bonebridge were respectively applied for the individuals with congenital outer and middle ear malformation. The study aim to explore the feasibility of personalized comprehensive treatment of congenital outer and middle ear malformation. Methods:We developed individualized surgical plans of Bonebridge implantation and auricular reconstruction for 35 patients with bilateral external and middle ear malformation. Six patients underwent Bonebridge implantation on one side, and the post-auricular skin expander implantation on the other sidesimultaneously; seven patients underwent Bonebridge implantation at the same time as the second stage of auricular reconstruction; twenty-two patients had their Bonebridge implantations performed after the reconstruction of the auricles. Results:No intraoperative complications occured in 35 patients. No facial paralysis, vertigo, tinnitus and cerebrospinal fluid leakage was reported. One patient had skin infection after Bonebridge implantation. The Bonebridge was removed and 7 months later and the Bonebridge implantation was re-performed on the same side. No complication occurred after 16 months of follow-up. Conclusion:According to the individual condition of the patients, different surgical plans of Bonebridge implantation and auricular reconstruction can be selected personally, which is beneficial to obtain the ideal aesthetic and hearing outcome.

Whole-Exome Sequencing of Discordant Monozygotic Twin Families for Identification of Candidate Genes for Microtia-Atresia.

OBJECTIVE: We used data from twins and their families to probe the genetic factors contributing to microtia-atresia, in particular, early post-twinning variations that potentially account for the discordant phenotypes of monozygotic twin pairs. METHODS: Six families of monozygotic twins discordant for congenital microtia-atresia were recruited for study. The six patients shared a consistent clinical phenotype of unilateral microtia-atresia. Whole-exome sequencing (WES) was performed for all six twin pairs and their parents. Family segregation and multiple bioinformatics methods were applied to identify suspicious mutations in all families. Recurring mutations commonly detected in at least two families were highlighted. All variants were validated via Sanger sequencing. Gene Ontology (GO) analysis was performed to identify candidate gene sets and related pathways. Copy number variation (CNV), linkage analysis, association analysis and machine learning methods were additionally applied to isolate candidate mutations, and comparative genomics and structural modeling tools used to evaluate their potential roles in onset of microtia-atresia. RESULTS: Our analyses revealed 61 genes with suspected mutations associated with microtia-atresia. Five (HOXA4, MUC6, CHST15, TBX10, and AMER1) contained 7 de novo mutations that appeared in at least two families, which have been previously reported as pathogenic for other diseases. Among these, HOXA4 (c.920A>C, p.H307P) was determined as the most likely pathogenic variant for microtia-atresia. GO analysis revealed four gene sets involving 11 pathways potentially related to underlying pathogenesis of the disease. CNVs in three genes (UGT2B17, OVOS, and KATNAL2) were detected in at least two families. Linkage analysis disclosed 13 extra markers for the disease, of which two (FGFR1 and EYA1) were validated via machine learning analysis as plausible candidate genes for the disease. CONCLUSION: Based on comprehensive genetic and bioinformatic analyses of WES data from six families of discordant monozygotic twins with microtia-atresia, we identified multiple candidate genes that may function in post-twinning onset of the disease. The collective findings provide novel insights into the pathogenesis of congenital microtia-atresia.

A Mutation in VWA1, Encoding von Willebrand Factor A Domain-Containing Protein 1, Is Associated With Hemifacial Microsomia.

BACKGROUND: Hemifacial microsomia (HFM) is a type of rare congenital syndrome caused by developmental disorders of the first and second pharyngeal arches that occurs in one out of 5,600 live births. There are significant gaps in our knowledge of the pathogenic genes underlying this syndrome. METHODS: Whole exome sequencing (WES) was performed on five patients, one asymptomatic carrier, and two marry-in members of a five-generation pedigree. Structure of WARP (product of VWA1) was predicted using the Phyre2 web portal. In situ hybridization and vwa1-knockdown/knockout studies in zebrafish using morpholino and CRISPR/Cas9 techniques were performed. Cartilage staining and immunofluorescence were carried out. RESULTS: Through WES and a set of filtration, we identified a c.G905A:p.R302Q point mutation in a novel candidate pathogenic gene, VWA1. The Phyre2 web portal predicted alterations in secondary and tertiary structures of WARP, indicating changes in its function as well. Predictions of protein-to-protein interactions in five pathways related to craniofacial development revealed possible interactions with four proteins in the FGF pathway. Knockdown/knockout studies of the zebrafish revealed deformities of pharyngeal cartilage. A decrease of the proliferation of cranial neural crest cells (CNCCs) and alteration of the structure of pharyngeal chondrocytes were observed in the morphants as well. CONCLUSION: Our data suggest that a mutation in VWA1 is functionally linked to HFM through suppression of CNCC proliferation and disruption of the organization of pharyngeal chondrocytes.

Comparative effects of unilateral and bilateral bone conduction hearing devices on functional hearing and sound localization abilities in patients with bilateral microtia-atresia.

Background: Various amplification options are available for patients with congenital bilateral conductive hearing loss. Unilateral bone conduction hearing device (BCHD) is widely used for these patients, whereas benefits of bilateral BCHDs in certain subgroups of patients require further exploration.Objectives: To evaluate functional and directional hearing in patients with unilateral Bonebridge (MEDEL) and contralateral ADHEAR (MEDEL) devices.Materials and methods: This study included 32 patients (20 males, 12 females), of mean age 11.8 years (range 7-27 years). Hearing thresholds, speech perception and sound localization were tested three months after activation of the Bonebridge under three conditions: unaided, unilateral BHCD (Bonebridge) and bilateral BHCDs (Bonebridge plus contralateral ADHEAR). Patient acceptance of these devices in daily life was evaluated by questionnaire.Results: Compared with unaided, the mean hearing thresholds (0.5, 1, 2, and 4 kHz) and speech perception with unilateral BCHD and bilateral BCHDs were improved significantly (p < .05 each). Markers of directional hearing ability, including percentages of accurate responses, bias angles and RMS errors, were significantly better with bilateral BCHDs than unilateral BHCD (p < .05 each). Questionnaire revealed high patient satisfaction with both unilateral and bilateral devices.Conclusions: Functional hearing and sound localization abilities were better with bilateral BCHDs than unilateral BCHD.

Investigating the effect of personality on left-turn behaviors in various scenarios to understand the dynamics of driving styles.

Objectives: To explore whether the driving style is static or dynamic, the purpose of this study was to investigate the effects of drivers' personality traits and driving scenarios on left-turn behaviors. We also evaluated drivers' perceptions in different situations to understand the occurrence of unreasonable driving behaviors.Methods: Two self-administered questionnaires were used to calculate participants' personality dimensions and driving style scores, respectively. Two experimental tasks were conducted by driving simulator with different weather, light, and speed of the opposing through vehicles.Results: Results showed that personality was significantly related to driving style. Neither the left-turn response process nor gap acceptance maneuvers were directly influenced by light conditions. In the test area, the average speed and the minimum speed of the left-turning vehicle, as well as the distance of the vehicle from the collision point when the speed is the smallest were significantly related to the weather, interaction type, and velocity difference, and the time to collision during which first brake or release gas pedal occurs was significantly related to velocity difference. Three out of the four driving conditions (except for light conditions) exhibited a statistically significant effect on the judgment of the arrival time of autonomous vehicles and their risk assessment, and personality was significantly related to risk assessment. Moreover, dangerous driving behavior was found to be significantly associated with drivers' driving personality.Conclusions: The driving style is dynamic and influenced by personality and driving conditions. Not only the wrong assessment of driving scenarios may lead to danger, but also the driver's personality characteristics such as self-interest, impulsively, and lack of self-confidence will lead to decision-making mistakes even when the judgment of driving scenarios is correct.

Comparison of three-dimensional and two-dimensional templates on auricle reconstruction in patients with unilateral microtia.

To confirm the advantage of 3D template over the traditional 2D template in auricle reconstruction. Two hundred patients with Marx III unilateral microtia treated in our hospital during the last four years were included in this retrospective study. They were divided into two groups according to the surgery which was assisted by 2D or 3D template. The outcome was evaluated 6 months after the surgery in the following aspects: the mean surgical time, the similarity rate for ear size, nasal-tip to tragus length and auriculocephalic angle, the patient's satisfaction and the quality of life after surgery. The surgical time for the 3D group was 3.2 ± 1.9 hours, significantly shorter than that for the 2D group (4.1 ± 3.7 hours; P < 0.05). The similarity rates between both sides were 91.24 ± 1.71%, 96.46 ± 2.51%, and 88.15 ± 10.20% respectively for ear size, nasal tip-tragus length, and auriculocephalic angle in the 3D group. While the corresponding values in the 2D group were smaller and were 87.47 ± 3.66%, 90.16 ± 3.27%, and 78.25 ± 1.26% respectively. The difference was significant in nasal tip-tragus length and auriculocephalic angle (P < 0.05), but not for ear size (P > 0.05). The patients' satisfaction was better in the 3D group. The averaged GCBI score was 65.6 ± 13.2 in the 3D group, which was significantly higher than the value of 55.3 ± 16.8 in the 2D group (P < 0.05). The use of 3D template resulted in a better outcome in the auricle reconstruction surgery.

Long-term Outcomes of Bone Conduction Hearing Implants in Patients With Bilateral Microtia-atresia.

OBJECTIVES: To evaluate the long-term outcomes of three different types of bone conduction hearing implants (BCHI)-BAHA, Ponto, and Bonebridge-in Mandarin-speaking patients with bilateral microtia-atresia. METHODS: This cohort study enrolled 59 patients affected by bilateral microtia-atresia, with an upper bone conduction threshold limit of 30 dB HL at frequencies of 0.5 to 4 kHz. All subjects underwent unilateral BCHI surgery, including 26 (18 males, 8 females, of mean age 8.7 ±â€Š1.9 yr) implanted with BAHA devices; 10 (7 males, 3 females, of mean age 11.7 ±â€Š2.8 yr) implanted with Ponto devices; and 23 (14 males, 9 females, of mean age 9.0 ±â€Š1.8 yr) implanted with Bonebridge devices. The main outcome measures included long-term audiological benefits, patient satisfaction, and complications. Each subject acted as his or her own control. RESULTS: Two years after BCHI surgery, the mean hearing thresholds in the BAHA, Ponto, and Bonebridge groups had improved to 22.6 ±â€Š1.6 dB HL, 21.6 ±â€Š1.2 dB HL, and 22.5 ±â€Š1.5 dB HL, respectively. The mean percentages of subjects in these three groups recognizing speech at 65 dB SPL under quiet conditions were 97.7 ±â€Š4.2%, 96.3 ±â€Š1.1%, and 94.4 ±â€Š9.4%, respectively, whereas the mean percentages recognizing speech under noise conditions (signal:noise ratio +5) were 87.0 ±â€Š1.8%, 89.3 ±â€Š9.3%, and 85.3 ±â€Š4.7%, respectively. Questionnaires revealed patients' benefits and satisfaction with this surgery. Three (11.5%) of 26 patients in the BAHA group and 1 (10%) of 10 in the Ponto group experienced skin irritation, but all recovered after local treatment. Five (19.2%) patients in the BAHA group and two (20%) in the Ponto experienced abutment extrusion about 6 months postoperatively, with all achieving good results after revision surgery to replace the abutment. One (3.8%) patient in the BAHA group experienced local chronic inflammation and underwent surgery to replace the BAHA with a Bonebridge implant. One (4.3%) patient in the Bonebridge group developed a local infection 3 months postoperatively and underwent implant removal. CONCLUSIONS: All three BCHIs were well tolerated after long-term follow-up, and all improved audiometric thresholds and the intelligibility of speech in the presence of both quiet and noise. These implants should be considered valid and safe options for the functional rehabilitation of patients with bilateral microtia-atresia.

TCOF1 pathogenic variants identified by Whole-exome sequencing in Chinese Treacher Collins syndrome families and hearing rehabilitation effect.

BACKGROUND: Treacher Collins syndrome (TCS, OMIM 154500) is an autosomal disorder of craniofacial development with an incidence rate of 1/50,000 live births. Although TCOF1, POLR1D, and POLR1C, have been identified as the pathogenic genes for about 90% TCS patients, the pathogenic variants of about 8-11% cases remain unknown. The object of this study is to describe the molecular basis of 14 clinically diagnosed TCS patients from four families using Whole-exome sequencing (WES) followed by Sanger sequencing confirmation, and to analyze the effect of bone conduction hearing rehabilitation in TCS patients with bilateral conductive hearing loss. RESULTS: Four previously unreported heterozygous pathogenic variants (c.3047-2A > G, c.2478 + 5G > A, c.489delC, c.648delC) were identified in the TCOF1 gene, one in each of the four families. Sanger sequencing in family members confirmed co-segregation of the identified TCOF1 variants with the phenotype. The mean pure-tone threshold improvements measured 3 months after hearing intervention were 28.8 dB for soft-band BAHA, 36.6 ± 2.0 dB for Ponto implantation, and 27.5 dB SPL for Bonebridge implantation. The mean speech discrimination improvements measured 3 months after hearing intervention in a sound field with a presentation level of 65 dB SPL were 44%, 51.25 ± 5.06, and 58%, respectively. All six patients undergoing hearing rehabilitation in this study got a satisfied hearing improvement. CONCLUSIONS: WES combined with Sanger sequencing enables the molecular diagnosis of TCS and may detect other unknown causative genes. Bone conduction hearing rehabilitation may be an optimal option for TCS patients with bilateral conductive hearing loss.

Outcomes of the Baha Attract System combined with auricle reconstruction in mandarin speaking patients with bilateral microtia-atresia.

BACKGROUND: A transcutaneous bone-conduction hearing device (tBCHD), the Baha Attract System has been recently introduced to China, and very few studies have assessed the efficacy of this system in speakers of mandarin. OBJECTIVES: This study aims to analyze the functional and cosmetic outcomes of this system. MATERIALS AND METHODS: This prospective study included 11 patients (nine males, two females), of mean age 16 years (range 9-32 years). Seven patients were conducted the implantation simultaneously with auricle reconstruction, and the other four were before it. Auditory results were compared between unaided patients and implanted patients. Subjective satisfaction was analyzed using three questionnaires. RESULTS: The mean sound field thresholds were 65.9 ± 5.1 dB SPL unaided and 30.9 ± 4.7 dB SPL with an implanted Baha Attract System, resulting in a mean hearing gain of 35.0 ± 6.7 dB. The mean WRS scores were 47.8 ± 8.7% unaided and 92.1 ± 2.0% with the Baha Attract System, resulting in a mean improvement of 47.8 ± 8.7%. No adverse events were reported and questionnaires showed good patients satisfaction. CONCLUSIONS: The transcutaneous Baha Attract System is effective in mandarin speaking patients, and the combination of hearing rehabilitation and auricle reconstruction surgery is promising for patients with bilateral microtia-atresia.

Identification of sequence variants associated with severe microtia-astresia by targeted sequencing.

BACKGROUND: Microtia-atresia is characterized by abnormalities of the auricle (microtia) and aplasia or hypoplasia of the external auditory canal, often associated with middle ear abnormalities. To date, no causal genetic mutations or genes have been identified in microtia-atresia patients. METHODS: We designed a panel of 131 genes associated with external/middle or inner ear deformity. Targeted genomic capturing combined with next-generation sequencing (NGS) was utilized to screen for mutations in 40 severe microtia-atresia patients. Mutations detected by NGS were filtered and validated. And then mutations were divided into three categories-rare or novel variants, low-frequency variants and common variants-based on their frequency in the public database. The rare or novel mutations were prioritized by pathogenicity analysis. For the low-frequency variants and common variants, we used association studies to explore risk factors of severe microtia-atresia. RESULTS: Sixty-five rare heterozygous mutations of 42 genes were identified in 27 (67.5%) severe microtia-atresia patients. Association studies to determine genes that were potentially pathogenic found that PLEC, USH2A, FREM2, DCHS1, GLI3, POMT1 and GBA genes were significantly associated with severe microtia-atresia. Of these, DCHS1 was strongly suggested to cause severe microtia-atresia as it was identified by both low-frequency and common variants association studies. A rare mutation (c.481C > T, p.R161C) in DCHS1 identified in one individual may be deleterious and may cause severe microtia-atresia. CONCLUSION: We identified several genes that were significantly associated with severe microtia-atresia. The findings provide new insights into genetic background of external ear deformities.

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.

Hearing improvement with softband and implanted bone-anchored hearing devices and modified implantation surgery in patients with bilateral microtia-atresia.

OBJECTIVE: To evaluate auditory development and hearing improvement in patients with bilateral microtia-atresia using softband and implanted bone-anchored hearing devices and to modify the implantation surgery. METHODS: The subjects were divided into two groups: the softband group (40 infants, 3 months to 2 years old, Ponto softband) and the implanted group (6 patients, 6-28 years old, Ponto). The Infant-Toddler Meaning Auditory Integration Scale was used conducted to evaluate auditory development at baseline and after 3, 6, 12, and 24 months, and visual reinforcement audiometry was used to assess the auditory threshold in the softband group. In the implanted group, bone-anchored hearing devices were implanted combined with the auricular reconstruction surgery, and high-resolution CT was used to assess the deformity preoperatively. Auditory threshold and speech discrimination scores of the patients with implants were measured under the unaided, softband, and implanted conditions. RESULTS: Total Infant-Toddler Meaning Auditory Integration Scale scores in the softband group improved significantly and approached normal levels. The average visual reinforcement audiometry values under the unaided and softband conditions were 76.75 ± 6.05 dB HL and 32.25 ± 6.20 dB HL (P < 0.01), respectively. In the implanted group, the auditory thresholds under the unaided, softband, and implanted conditions were 59.17 ± 3.76 dB HL, 32.5 ± 2.74 dB HL, and 17.5 ± 5.24 dB HL (P < 0.01), respectively. The respective speech discrimination scores were 23.33 ± 14.72%, 77.17 ± 6.46%, and 96.50 ± 2.66% (P < 0.01). CONCLUSIONS: Using softband bone-anchored hearing devices is effective for auditory development and hearing improvement in infants with bilateral microtia-atresia. Wearing softband bone-anchored hearing devices before auricle reconstruction and combining bone-anchored hearing device implantation with auricular reconstruction surgery may bethe optimal clinical choice for these patients, and results in more significant hearing improvement and minimal surgical and anesthetic injury.