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. 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. 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.

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. 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. 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. We identified several genes that were significantly associated with severe microtia-atresia. The findings provide new insights into genetic background of external ear deformities.

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.

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.