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 ± 1.9 yr) implanted with BAHA devices; 10 (7 males, 3 females, of mean age 11.7 ± 2.8 yr) implanted with Ponto devices; and 23 (14 males, 9 females, of mean age 9.0 ± 1.8 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 ± 1.6 dB HL, 21.6 ± 1.2 dB HL, and 22.5 ± 1.5 dB HL, respectively. The mean percentages of subjects in these three groups recognizing speech at 65 dB SPL under quiet conditions were 97.7 ± 4.2%, 96.3 ± 1.1%, and 94.4 ± 9.4%, respectively, whereas the mean percentages recognizing speech under noise conditions (signal:noise ratio +5) were 87.0 ± 1.8%, 89.3 ± 9.3%, and 85.3 ± 4.7%, 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.

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.

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.