Changes in Listening Effort Through Pupil Response After Atresioplasty in Children With Congenital Aural Atresia.

OBJECTIVES: This study aimed to determine whether the improvement of hearing by surgical treatment alleviates cognitive demands through pupil response in patients with unilateral congenital aural atresia (CAA). DESIGN: A prospective study was performed on patients with unilateral CAA who were scheduled to undergo primary atresioplasty between November 2017 and May 2020. Pure-tone audiometry, auditory digit span test, Korean Speech Perception in Noise test, pupil measurement during speech tests, and questionnaires (Sound-Spatial-Qualities of Hearing Scale; subjective listening effort rating) were performed before and 6 months after surgery. RESULTS: Of 30 consecutive patients who initially enrolled, only 18 patients (12 males and 6 females) were included in the analysis. When the improvement of the air-bone gap and interaural difference of air conduction within 30 dB was defined as a successful hearing outcome, successful hearing improvement was achieved in 50% of the 18 patients. In pupil measurement, the success group had a significantly smaller mean pupil dilation response than the nonsuccess group at 0 and -3 dB signal to noise ratio (SNR) (all p < 0.01). In addition, significant differences were identified between the two groups for peak dilation and peak latency at all noise levels (all p < 0.01). When analyzing the change in pupil response before and after surgery, the difference in relative mean pupil dilation in the success group was significantly greater than that in the nonsuccess group at -3 dB SNR ( p = 0.02). In addition, the success group showed a significantly greater change in peak latency than the nonsuccess group at the -3 dB SNR ( p < 0.01). The difference in peak dilation tended to be greater in the success group than in the nonsuccess group, but the difference was not statistically significant. CONCLUSIONS: Patients with unilateral CAA who achieved surgically improved hearing had a smaller pupil dilation response than those who did not. These results suggest that successful hearing outcomes after surgery in patients with unilateral CAA may reduce the cognitive effort required to understand speech under difficult listening conditions.

A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Clinical and molecular cytogenetic findings of cat eye syndrome and a 2-year-old patient with congenital aural atresia and hearing loss.

BACKGROUND: Cat eye syndrome (CES) is a rare congenital disease frequently caused by a partial tetrasomy of the proximal long (q) arm of chromosome 22, due to a small supernumerary marker chromosome (sSMC). CES patients show remarkable phenotypic variability. Despite the progress of molecular cytogenetic technology, the cause of phenotypic variability and the genotype-phenotype correlations remain unknown. METHODS: We analyzed clinical and genetic data of a new patient with CES together with 27 previously reported ones with a confirmed genomic gain in the PubMed database between 2012 and 2023. RESULTS: We reported a boy with CES carrying a 22q11.1-q11.21 duplication of 1.76 Mb tetrasomy (16888900_18644241, hg19) who presented currently rare or unreported clinical findings such as congenital aural atresia, hearing loss, PLSVC, and IVC. The results of the whole exome sequencing (WES) showed a heterozygous mutation of the GJB2 gene (NM_004004.6: exon2: c.109G > A). In addition, the results of our literature review showed that the presence of a classical sSMC was the most frequent cytogenetic abnormality in CES (82%). 63% of cases were in a homogenous state and 37% of cases were in a mosaic state. 72% of cases had a 1-2 Mb duplication. In the majority of CES patients the breakpoints in chromosome 22 are localized to a 50 kb region (18610000_18660000 bp). The CES critical region (CESCR) may be further delimited to a 0.3 Mb region (17799398_18111588 bp). Within this region CECR2, SLC25A18, ATP6V1E1, and BCL2L13 are strong candidate genes for causing the main CES phenotype. The ear anomalies are the most frequent features in CES patients (89%) and hearing loss was present in 36% of CES patients. CONCLUSIONS: The phenotypic features in CES are highly variable. Our findings expand the symptom spectrum of CES and lay the foundation for better delineating the clinical phenotype, molecular cytogenetic features associated with CES and genotype-phenotype correlations. We recommend performing WES to rule out the involvement of other genetic factors in the patient's phenotype. In addition, our findings also highlight the need for genetic counseling and recurrence risk assessment.

Clinical evaluation of temporal bone anatomical abnormalities and surgical method selection in patients with congenital aural atresia.

OBJECTIVES: To analyze anatomic variations of the temporal bone in congenital aural atresia (CAA) and their correlation with the Jahrsdoerfer score, in order to guide clinical selection of surgical treatment methods. MATERIAL AND METHODS: We retrospectively studied 53 patients (72 ears) with unilateral or bilateral CAA, including 34 ears with normal hearing as controls. Audiological and imaging data were collected and analyzed. We evaluated the Jahrsdoerfer score and anatomical variations, including tegmen mastoideum position, anterior sigmoid sinus displacement, and elevated jugular bulb. RESULTS: The average air conduction hearing threshold (PTA4) ranged from 0.5 to 4 kHz was 65.48 ± 8.19 dBHL, with an average Jahrsdoerfer score of 4.93 ± 2.78. In CAA group, there was a higher prevalence and severity of anterior sigmoid sinus and low position of the tegmen mastoideum (P < 0.01). However, there was no significant difference in incidence rates among groups with high jugular bulb (P > 0.05). Anterior sigmoid sinus and high jugular bulb showed no correlation with the Jahrsdoerfer score, while the low position of the tegmen mastoideum had a weak correlation. The Jahrsdoerfer score did not adequately predict temporal bone anatomical abnormalities in CAA patients. CONCLUSION: CAA exhibit a higher incidence and greater severity of temporal bone anatomical abnormalities compared to the control group, and the Jahrsdoerfer score inadequately assesses these abnormalities. Anomalies like low position of the tegmen mastoideum, anterior sigmoid sinus, and high jugular bulb should also be considered as independent factors influencing surgical decisions for atresiaplasty.

Long-term results and quality of life after vibrant soundbridge implantation (VSBs) in children and adults with aural atresia.

PURPOSE: The aim of this study was to evaluate the long-term effectiveness and acceptance of the active middle ear implant system Vibrant Soundbridge (VSB®, MED-EL, Austria) in patients with aural atresia or aplasia (children and adults). METHODS: Data from 51 patients (mean age 13.9 ± 11.3 years), 42 (79.2%) children and adolescents, and 11 (20.8%) adults) who received a VSB implant between 2009 and 2019 at the Department of Otolaryngology at LMU Clinic Großhadern, Munich were included in the study. Pure-tone audiometry, speech recognition in a quiet environment and in a noisy environment were performed preoperatively, during the first fitting of the audio processor, after 1-3 years, after 3-5 years, and after 5 years (if possible). The follow-up period ranged from 11 to 157 months with a mean of 58.6 months (4.8 years). Furthermore, the benefit of the VSB was evaluated by self-assessment questionnaires (Speech, Spatial, and Qualities of Hearing Scale, respectively, for parents). RESULTS: Significant improvements were observed in hearing and speech comprehension immediately after the initial fitting of the VSB system (mean hearing gain 38.4 ± 9.4 dB HL) and at follow-up intervals (1-3, 3-5 and after 5 years) for children and adults (p < 0.01). The values remained stable over the long-term, indicating a sustained functional gain from the VSB (mean hearing gain 38.9 ± 9.2 dB HL). The results of the self-assessments affirm the positive influence on hearing and speech comprehension with the VSB. With the VSB, there was an improvement of 41.3 ± 13.7% in the Freiburg monosyllable test. CONCLUSION: These results (a stable hearing gain over the long term, a good tolerance of the implant and an improvement in quality of life) affirm the recommendation for using the active middle ear implant VSB as early as permitted for aural atresia and aplasia patients. This study represents the audiometric results with the (to date) largest collective of aural atresia patients and with a long follow-up period.

Efficacy of vibrant sound bridge in congenital aural atresia: an updated systematic review.

PURPOSE: The indications of Vibrant Soundbridge (VSB) have been expanded to include patients with conductive and mixed hearing loss due to congenital aural atresia (CAA). However, the current evidence supporting the auditory outcomes of VSB is based mainly on case reports and retrospective chart reviews. Therefore, the present systematic review aims to summarize and critically appraise the current evidence regarding the safety and effectiveness of VSB in children and adult patients with CAA. METHODS: A systematic literature search retrieved studies that evaluated the outcomes of unilateral or bilateral implantation of VSB in patients with CAA. The bibliographic search was conducted in PubMed, Scopus, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from January 2000 to December 2022. RESULTS: Twenty-seven studies were included in the present systematic review. Overall, the speech perception after VSB was good, with a mean word recognition score (WRS) score ranging from 60 to 96.7%. The mean postoperative speech recognition threshold (SRT) after implantation ranged from 20.8 to 50 dB. The effective gain was reported in 15 studies, ranging from 31.3 to 45.5 dB. In terms of user satisfaction with VSB, the included studies showed significant improvements in the patient-reported outcomes, such as the Speech Spatial and Qualities of Hearing scale and Glasgow Hearing Aid Benefit Profile. The VSB implantation was generally safe with low incidence of postoperative complications. CONCLUSION: VSB provides significant benefits to individuals with hearing loss owing to CAA, with very good subjective outcomes and a low risk of complications.

Question Mark Ear: An Unusual Anomaly and a Novel Surgical Technique for Reconstruction.

The question mark ear is a rare abnormality characterized by a cleft between the helix and the earlobe, resulting in a protrusion of the upper part of the ear. The severity of this ear malformation can range from a minor notch in the helix to a complete separation of the helix and the earlobe. In this study, we present a case of a patient with a moderately severe right-sided unilateral question mark deformity. To address this issue, we utilized a novel technique that involves a combination of a Y-V flap with double opposing Z-plasty. Our clinical study demonstrates that using this technique for reconstructing the deformity yields excellent results in terms of the helical rim and fold contour, utilizing solely the local tissues.

[Improved radiological imaging of congenital aural atresia using flat-panel volume CT. German version]. / Verbesserte radiologische Darstellung kongenitaler Auralatresien mittels "flat-panel volume CT".

BACKGROUND: Precise preoperative radiological evaluation of aural atresia is of utmost importance for surgical planning. Until now, multislice computed tomography (MSCT) has been used but it cannot adequately visualize small structures such as the stapes. Flat-panel volume CT (fpVCT) with its secondary reconstructions (fpVCTSECO) offers a high-resolution visualization of the middle ear. New otosurgical planning software also enables detailed 3D reconstruction of the middle ear anatomy. AIM OF THE WORK: Evaluation of the use of fpVCTSECO in combination with an otosurgical planning software for a more accurate diagnosis and treatment of congenital aural atresia. MATERIAL AND METHODS: Seven patients with congenital aural atresia underwent preoperative MSCT (600 µm slice thickness) and corresponding fpVCT (466 µm slice thickness). In addition, fpVCTSECO (99 µm slice thickness) were reconstructed. The Jahrsdoerfer and Siegert grading scores were determined and their applicability in the abovementioned imaging modalities was evaluated. In addition, the malleus incus complex was analyzed in 3D rendering. RESULTS: Imaging with fpVCTSECO enabled reliable visualization of the abnormalities, in particular the ossicular chain. A significant difference in the Siegert grading score was found. In addition, the malleus-incus complex could be visualized better in 3D. DISCUSSION: The introduction of new imaging techniques and surgical planning techniques into the diagnostic concept of aural atresia facilitates the identification of malformed anatomy and enables systematic analysis. This combination can also help to more accurately classify the pathology and thus increase the safety and success of the surgical procedure.

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report.

BACKGROUND: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. CASE PRESENTATION: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. CONCLUSIONS: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

Damaging variants in FOXI3 cause microtia and craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. METHODS: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. RESULTS: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. CONCLUSION: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.

New locus underlying auriculocondylar syndrome (ARCND): 430 kb duplication involving TWIST1 regulatory elements.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia and auricular malformations. To date, pathogenic variants have been identified in three genes involved in the EDN1-DLX5/6 pathway (PLCB4, GNAI3 and EDN1) and some cases remain unsolved. Here we studied a large unsolved four-generation family. METHODS: We performed linkage analysis, resequencing and Capture-C to investigate the causative variant of this family. To test the pathogenicity of the CNV found, we modelled the disease in patient craniofacial progenitor cells, including induced pluripotent cell (iPSC)-derived neural crest and mesenchymal cells. RESULTS: This study highlights a fourth locus causative of ARCND, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7 defined by linkage analysis. This duplication segregates with the disease in the family (LOD score=2.88) and includes HDAC9, which is located over 200 kb telomeric to the top candidate gene TWIST1. Notably, Capture-C analysis revealed multiple cis interactions between the TWIST1 promoter and possible regulatory elements within the duplicated region. Modelling of the disease revealed an increased expression of HDAC9 and its neighbouring gene, TWIST1, in neural crest cells. We also identified decreased migration of iPSC-derived neural crest cells together with dysregulation of osteogenic differentiation in iPSC-affected mesenchymal stem cells. CONCLUSION: Our findings support the hypothesis that the 430 kb duplication is causative of the ARCND phenotype in this family and that deregulation of TWIST1 expression during craniofacial development can contribute to the phenotype.

The advantages of domestic ear molding system in molding bilateral neonatal congenital auricular deformities.

BACKGROUND: There are different types of ear molding devices on the market. However, due to high cost, the wide application of the ear molding is hindered, especially for children with bilateral congenital auricular deformities (CAD). This study is designed to correct the bilateral CAD with the flexible use of Chinese domestic ear molding system. METHODS: Newborns diagnosed with bilateral CAD were recruited in our hospital from September 2020 to October 2021. For each subject, one ear wore a set of domestic ear molding system, while the contralateral ear used only matching Retractor and Antihelix Former. Medical charts were reviewed to collect data on the types of CAD, the incidence of complications, the initiation and duration of treatment, as well as the satisfaction after treatment. Treatment outcomes were graded into three levels: excellent, good, and poor, according to the improvement of auricular morphology evaluated by both doctors and parents, respectively. RESULTS: A total of 16 infants (32 ears) were treated with the Chinese domestic ear molding system, which contains 4 cases with Stahl's ear (8 ears), 5 cases with Helical rim deformity (10 ears), 3 cases with Cup ear (6 ears), 4 cases with Lop ear (8 ears). All infants accomplished the correction completely. Both parents and doctors were satisfied with the outcomes. No obvious complication was observed. CONCLUSIONS: Ear molding is an effective nonsurgical treatment for CAD. Molding with Retractor and Antihelix Former is simple and effective. Domestic ear molding system can be flexibly used in correcting bilateral CAD. With this approach, infants with bilateral CAD will benefit more in the near future.

Pediatric cholesteatoma associated with congenital aural atresia and stenosis.

OBJECTIVE: Investigate presenting features, associated surgical treatment, and outcomes in patients with cholesteatoma associated with congenital aural atresia (CAA) or stenosis (CAS). METHODS: Colorado Multiple Institution Review Board approval was obtained. A retrospective chart review was performed at a single tertiary care children's hospital of all pediatric patients with congenital aural atresia or stenosis with associated cholesteatoma from January 1, 2003, to October 15, 2018. RESULTS: Of the 278 patients identified with CAA or CAS, twelve (4.3 %) were found to have a canal cholesteatoma. There was a male predominance (8:4). Nine patients (75 %) had conductive loss and three (25 %) had mixed loss. Four patients (33.3 %) exhibited canal cholesteatomas extending into the middle ear or mastoid cavity. All patients underwent surgery, and 25 % of patients required revision canalplasty while 58 % of patients required revision surgery for cholesteatoma recidivism. The average age at the time of surgery was 11.3 ± 3.7 years. CONCLUSION: Fewer than 5 % of pediatric patients with congenital aural atresia or stenosis were diagnosed with an acquired canal cholesteatoma. The need for revision surgery was common, occurring in >50 % of cases. Screening patients with CAA/CAS for cholesteatoma with imaging is recommended to avoid the morbidity of delayed identification.

Search for a genetic cause in children with unilateral isolated microtia and congenital aural atresia.

PURPOSE: Microtia describes a spectrum of auricular malformations ranging from mild dysplasia to anotia. A vast majority of microtia patients demonstrate congenital aural atresia (CAA). Isolated microtia has a right ear predominance (58-61%) and is more common in the male sex. Isolated microtia is a multifactorial condition involving genetic and environmental causes. The aim of this study is to describe the phenotype of children with unilateral isolated microtia and CAA, and to search for a common genetic cause trough DNA analysis. METHODS: Phenotyping included a complete clinical examination. Description on the degree of auricular malformation (Weerda classification-Weerda 1988), assessment for hemifacial microsomia and age-appropriate audiometric testing were documented. Computerized tomography of the temporal bone with 3-D rendering provided a histopathological classification (HEAR classification-Declau et al. 1999). Genetic testing was carried out by single nucleotide polymorphism (SNP) microarray. RESULTS: Complete data are available for 44 children (50% was younger than 33 days at presentation; 59.1% boys; 72.7% right ear). Type III microtia was present in 28 patients. Type 2b CAA existed in 32 patients. All patients had a normal hearing at the non-affected side. Genome wide deletion duplication analysis using microarray did not reveal any pathological copy number variant (CNV) that could explain the phenotype. CONCLUSIONS: Type III microtia (peanut-shell type) in combination with a type 2b CAA was the most common phenotype, present in 23 of 44 (52.3%) patients with isolated unilateral microtia. No abnormalities could be found by copy number variant (CNV) analysis. Whole exome sequencing in a larger sample with a similar phenotype may represent a future diagnostic approach.

Auriculocondylar syndrome: Pathogenesis, clinical manifestations and surgical therapies.

Auriculocondylar syndrome (ARCND) is a genetic and rare craniofacial condition caused by abnormal development of the first and second pharyngeal arches during the embryonic stage and is characterized by peculiar auricular malformations (question mark ears), mandibular condyle hypoplasia, micrognathia and other less-frequent features. GNAI3, PLCB4 and EDN1 have been identified as pathogenic genes in this syndrome so far, all of which are implicated in the EDN1-EDNRA signal pathway. Therefore, ARCND is genetically classified as ARCND1, ARCND2 and ARCND3 based on the mutations in GNAI3, PLCB4 and EDN1, respectively. ARCND is inherited in an autosomal dominant or recessive mode with significant intra- and interfamilial phenotypic variation and incomplete penetrance, rendering its diagnosis difficult and therapies individualized. To raise clinicians' awareness of the rare syndrome, we focused on the currently known pathogenesis, pathogenic genes, clinical manifestations and surgical therapies in this review.

Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases.

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Bilateral choanal stenosis in auriculocondylar syndrome caused by a PLCB4 variant.

Auriculocondylar syndrome (ARCND) is characterized by a distinguished feature of question mark ears and a variation of other minor and major malformations. Monoallelic or biallelic PLCB4 variants have been reported in a subset of affected individuals, referred to as ARCND2. We report on a 3-year-old female with ARCND who presented at birth with question mark ears, micrognathia, and bilateral choanal stenosis that was characterized by difficulty in breathing. She was found to be heterozygous for a novel PLCB4 variant, p.Glu358Gly. Respiratory distress is rare in autosomal dominant ARCND2 and choanal stenosis has not been reported. Our study expands the clinical phenotype of ARCND by adding choanal stenosis as a finding and suggests that PLCB4 play a role in the development of choanal structures.

A novel MBTPS2 variant associated with BRESHECK syndrome impairs sterol-regulated transcription and the endoplasmic reticulum stress response.

Ichthyosis follicularis, atrichia, and photophobia syndrome (IFAP syndrome) is a rare, X-linked disorder caused by pathogenic variants in membrane-bound transcription factor protease, site 2 (MBTPS2). Pathogenic MBTPS2 variants also cause BRESHECK syndrome, characterized by the IFAP triad plus intellectual disability and multiple congenital anomalies. Here we present a patient with ichthyosis, sparse hair, pulmonic stenosis, kidney dysplasia, hypospadias, growth failure, thrombocytopenia, anemia, bone marrow fibrosis, and chronic diarrhea found by research-based exome sequencing to harbor a novel, maternally inherited MBTPS2 missense variant (c.766 G>A; (p.Val256Leu)). In vitro modeling supports variant pathogenicity, with impaired cell growth in cholesterol-depleted media, attenuated activation of the sterol regulatory element-binding protein pathway, and failure to activate the endoplasmic reticulum stress response pathway. Our case expands both the genetic and phenotypic spectrum of BRESHECK syndrome to include a novel MBTPS2 variant and cytopenias, bone marrow fibrosis, and chronic diarrhea.

Disparities in Speech and Language Delay Among Children With Aural Atresia.

OBJECTIVE: To describe risk factors for speech and language delay in a diverse population of children with aural atresia. METHODS: Retrospective chart review was performed from 2012 to 2020 at UCSF Benioff Children's Hospital to identify children with aural atresia evaluated for speech, language, or auditory skills delays. Ninety-five children with aural atresia, conductive hearing loss, and assessment of speech, language, or auditory skills delay were included. Demographic and clinical data were analyzed to identify predictors of speech and language delay. Cohort and case-control analyses were performed to determine risk factors for delayed intervention, and for ultimate delays in speech, language, or auditory skills. RESULTS: Children exhibited a wide diversity of race/ethnicity, primary home language, geography, and insurance status. Eighty-nine percent had unilateral aural atresia. Forty-eight percent had delays in speech, language, or auditory skills. Most children used hearing aids (84%), had educational accommodations (84%), and received speech therapy (63%). In a univariate retrospective cohort analysis, public-insured ( p = 0.004), non-English speaking ( p = 0.002) and non-white/non-Hispanic children ( p = 0.007) were found to be significantly less likely to be fit with hearing aids in infancy. Children with delays were fit with hearing aids at later ages. In a multivariate case-control analysis, primary home language was a significant predictor for presence of delays [OR, 3.9 (95% CI: 1.2-13.2), p = 0.03]. CONCLUSIONS: Disparities due to insurance type, primary language, and race/ethnicity are associated with delays in hearing aid fitting for children with aural atresia. Earlier, hearing amplification is correlated with reduced risk for speech, language, and auditory skills delay. These findings can help identify at-risk children for targeted support.

Audiological results and subjective benefit of an active transcutaneous bone-conduction device in patients with congenital aural atresia.

PURPOSE: To review functional and subjective benefit after implantation of an active transcutaneous bone conduction device (BCD) in patients with congenital microtia with atresia or stenosis of the external auditory canal. METHODS: Retrospective chart analysis and questionnaire on the subjective impression of hearing ( Speech, Spatial and Qualities of Hearing Scale (SSQ-B) of patients treated between 2012 and 2015. RESULTSRESULTS: 18 patients (24 ears) with conductive or mixed hearing loss in unilateral (n = 10) or bilateral (n = 8) atresia were implanted with a BCD. No major complications occurred after implantation. Preoperative unaided air conduction pure tone average at 0.5, 1, 2 and 4 kHz (PTA 4 ) was 69.2 ± 11.7 dB, while postoperative aided PTA 4 was 33.4 ± 6.3 dB, resulting in a mean functional hearing gain of 35.9 +/- 15.6 dB. Preoperatively, the mean monosyllabic word recognition score was 22.9 % ± 22.3 %, which increased to 87.1 % +/- 15.1 % in the aided condition. The Oldenburger Sentence Test at S0N0 revealed a decrease in signal-to-noise-ratio from - 0.58 ± 4.40 dB in the unaided to - 5.67 ± 3.21 dB in the postoperative aided condition for all patients investigated. 15 of 18 patients had a subjective benefit showing a positive SSQ-B score (mean 1.7). CONCLUSION: The implantation of an active bone conduction device brings along subjective and functional benefit for patients with conductive or combined hearing loss.