Coexisting presentation of two rare genetic variants of autosomal dominant polycystic kidney disease and Alport syndrome.

Alport syndrome and autosomal dominant polycystic kidney disease are monogenic causes of chronic kidney disease and end-stage kidney failure. We present a case of a man in his 60s with progressive chronic kidney disease, bilateral sensorineural hearing loss and multiple renal cysts. Genetic analysis revealed a heterozygous variant in COL4A3 (linked to Alport syndrome) and in the GANAB gene (associated with a milder form of autosomal dominant polycystic kidney disease). Although each variant confers a mild risk of developing end-stage kidney disease, the patient presented a pronounced and accelerated progression of chronic kidney disease, which goes beyond what would be predicted by adding up their individual effects. This suggests a potential synergic effect of both variants, which warrants further investigation.

Management of oral manifestations of a child with Heimler Syndrome-2.

Heimler Syndrome 2 (HS-2) is a rare, autosomal recessive mild form of a peroxisomal biogenesis disorder. Though knowledge regarding the disorder is limited, emerging research has found that sensorineural hearing loss, occasional or late onset pigmentation, amelogenesis imperfecta and nail abnormalities are clinical characteristics representative of HS-2.A school-aged male presented to the dental department with a chief complaint of a lack of enamel on multiple teeth. The patient's medical history was significant for patent ductus arteriosus, bilateral sensorineural hearing loss and biallelic mutation of the PEX6 gene. The clinical exam revealed dental crowding, hypoplasia, hypo-calcification of multiple teeth and enlarged pulp chambers of maxillary molars. This case report details the clinical findings associated with HS-2, the comprehensive dental treatment to be rendered to the patient, and critical information to paediatric dentists and general dentists so that they can make proper referrals to medical specialties.

Remote or in-clinic? The effect of service delivery mode on hearing aid output: study protocol for a double-blinded, randomised trial in adults with mild to moderate sensorineural hearing loss.

BACKGROUND: Teleaudiology can potentially improve access to hearing healthcare services. Remote hearing aid fittings offer a new mode of service delivery that removes barriers of geography and access to an audiologist. Real-ear measurements (REMs) are the gold standard for hearing aid output verification but require in-clinic appointments. This study will investigate whether remote hearing aid fittings can provide clinically equivalent outcomes when compared to current, in-clinic, best practice guidelines. RESEARCH DESIGN: A repeated measure, double-blinded crossover design will be used. Participants will be randomly allocated to one of two groups to determine order of intervention, balanced for degree of hearing loss. STUDY SAMPLE: Sixty adults with mild to moderate hearing loss and at least 1 year of experience with hearing aids will be recruited. DATA COLLECTION AND ANALYSIS: Participants will complete two hearing aid fitting protocols, one using an in-clinic fitting process and the other using a remote (at-home) fitting process. In-clinic fittings will include REMs with adjustments to standard (NAL-NL2) prescription targets. The two fitting protocols will then be randomly assigned to participants in a crossover design, so participants and researchers will be blinded to the order of the two fitting protocols. Participants will then have a 4-week period with follow-up appointments for participant-directed gain adjustment. For each fitting protocol, participants will complete objective measurements of final hearing aid output with REMs, speech-in-noise testing, subjective measurements of hearing aid performance, and quality of life measurements. They will then begin an identical period of living with, adjusting, and objective assessment with the other fitting protocol. Data will be analysed as repeated measures with statistical control for potential confounding variables. RESULTS: Data will compare the four-frequency average real-ear aided response (4FREAR) for hearing aids programmed in-clinic and hearing aids programmed remotely, after participant-directed gain adjustments. Secondary measures will assess clinically significant differences in estimated speech intelligibility, hearing-related quality of life, hearing aid benefit, sound quality and preference, and speech-in-noise ability. CONCLUSIONS: This study will inform the development of best practice guidelines for remote hearing aid fittings. If no clinically significant differences are found between in-clinic and remote fit hearing aids, it has the potential to expand teleaudiology initiatives. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12623000028606p . Date of registration: 12 January 2023.

[Clinical features of congenitally enlarged bony portion of Eustachian tube].

Objective:To investigate the clinical features of patients with congenitally enlarged bony portions of the Eustachian tube（ET）. Methods:The medical history, physical examination, hearing test, temporal bone high resolution computed tomography（HRCT） of six patients（nine ears） with congenitally enlarged bony portion of the ET were retrospectively analyzed. Results:Four patients were men and two were women. The minimum, maximum, and average ages were 5, 21, and（14.7±6.4） years, respectively. Three malformations were bilateral and three were left-sided. Three ears had conductive hearing loss（average bone and air conduction thresholds were 13.7 dB and 71.3 dB）, three had mixed hearing loss（average bone and air conduction thresholds were 27.7 dB and 83.7 dB）, and one had extremely severe sensorineural hearing loss. The average maximum length and width of the enlarged bony ET on temporal bone HRCT were（22.61±2.94） mm and（6.50±2.33） mm, respectively. The enlargement was combined with an external auditory canal malformation in six ears, narrow tympanic cavity in six, tympanic antrum malformation in five, ossicular chain malformation in seven, cochlear malformation in six, helicotrema malformation in three, vestibule widening in two, semicircular canal malformation in three, vestibular window malformation in six, facial nerve abnormality in five, internal auditory meatus malformation in two, low middle cranial fossa in eight, and severe internal carotid artery malformation in one. Conclusion:Bony ET enlargement is a rare congenital middle ear malformation which could combined with other ear malformations. Patients can have no ET dysfunction but different patterns of hearing loss. The defect is usually found unintentionally during imaging, and the HRCT of temporal bone is significant.

Clinical Reasoning: A 24-Year-Old Man With Gait Impairment, Hearing Loss, and Recurrent Fever.

We present a case study of a 24-year-old man who reported mild balance and walking difficulties for 2 years. He had a history of recurrent fever, skin lesions, headache, and elbow pain, but most of these events resolved spontaneously. There was no significant family history. On examination, we observed frontal bossing, sensorineural hearing loss, and gait ataxia. This case underscores the significance of identifying clinical indicators in patients with neurologic symptoms, particularly recurrent fever, to establish a precise and thorough differential diagnosis.

Actinomycetoma in a patient with pre-existing sensorineural hearing loss: a linezolid-based treatment paradigm.

Mycetoma is a chronic granulomatous infectious disease with a triad of subcutaneous swelling, discharging sinuses and the presence of granules. The infection may occur following minor trauma or penetrating thorn injury. We report a case of a man in his 40s with a history of thorn prick 9 years ago, followed by the formation of painless discharging sinuses on the right foot for the past 2 years. Clinical, local epidemiological, histopathological examination and Gram stain confirmed the diagnosis of actinomycetoma. Prior to initiating the Welsh regimen, a pretreatment assessment of the patient's auditory function was conducted through pure tone audiometry, indicating the existence of pre-existing high-frequency bilateral sensorineural hearing loss. The patient was treated with linezolid as an alternative to amikacin, at a dosage of 600 mg two times per day, leading to complete resolution within 3 weeks. This underscores linezolid's efficacy as a safe and cost-effective alternative for actinomycetoma, without causing ototoxic side effects.

Diagnóstico genético de la hipoacusia neurosensorial infantil / Genetic diagnosis of childhood sensorineural hearing loss

Introducción: La hipoacusia neurosensorial (HNS) congénita o de inicio precoz es una de las enfermedades hereditarias más frecuentes en nuestro medio y es la deficiencia sensorial más frecuente. Es importante realizar un estudio etiológico de la hipoacusia y el estudio genético mediante la secuenciación de nueva generación (NGS) es la prueba con mayor rendimiento diagnóstico. Nuestro estudio muestra los resultados genéticos obtenidos en una serie de pacientes con HNS congénita/de inicio precoz bilateral. Material y método: Se incluyeron 105 niños diagnosticados de HNS bilateral a los que se les realizó un estudio genético entre los años 2019 y 2022. El estudio genético consistió en una secuenciación masiva del exoma completo, filtrando el análisis para los genes incluidos en un panel virtual de hipoacusia con 244 genes. Resultados: Se obtuvo un diagnóstico genético en 48% (50/105) de los pacientes. Se detectaron variantes patogénicas y probablemente patogénicas en 26 genes diferentes, siendo los genes más frecuentemente afectados el gen GJB2, USH2A y STRC. De las variantes detectadas 52% (26/50) se asociaron a una hipoacusia no sindrómica, 40% (20/50) una hipoacusia sindrómica y 8% restante (4/50) se podían asociar tanto a una hipoacusia sindrómica como no sindrómica. Conclusiones: El estudio genético constituye una parte fundamental del diagnóstico etiológico de la HNS bilateral. Nuestra serie muestra que el estudio genético de la hipoacusia mediante NGS tiene un alto rendimiento diagnóstico y nos proporciona información de gran utilidad en la práctica clínica.(AU)

Introduction: Congenital/early-onset sensorineural hearing loss (SNHL) is one of the most common hereditary disorders in our environment. There is increasing awareness of the importance of an etiologic diagnosis, and genetic testing with next-generation sequencing (NGS) has the highest diagnostic yield. Our study shows the genetic results obtained in a cohort of patients with bilateral congenital/early-onset SNHL. Materials and methods: We included 105 children with bilateral SNHL that received genetic testing between 2019 and 2022. Genetic tests were performed with whole exome sequencing, analyzing genes related to hearing loss (virtual panel with 244 genes). Results: 48% (50/105) of patients were genetically diagnosed. We identified pathogenic and likely pathogenic variants in 26 different genes, and the most frequently mutated genes were GJB2, USH2A and STRC. 52% (26/50) of variants identified produced non-syndromic hearing loss, 40% (20/50) produced syndromic hearing loss, and the resting 8% (4/50) could produce both non-syndromic and syndromic hearing loss. Conclusions: Genetic testing plays a vital role in the etiologic diagnosis of bilateral SNHL. Our cohort shows that genetic testing with NGS has a high diagnostic yield and can provide useful information for the clinical workup of patients.(AU)

Impact Of Sensorineural Hearing Loss On Subjective Tinnitus Quality In Patients With Bilateral Tinnitus.

INTRODUCTION: Tinnitus is a frequent condition that indicates the sensation of sound in the absence of a corresponding external stimulus and can significantly impair the quality of life. The main risk factor for developing tinnitus is hearing loss. The diagnosis of tinnitus is based on history, assessment of tinnitus severity, clinical examination, and audiological tests. The main purpose of this research was to examine the relationship between the presence and level of hearing loss and the characteristics of tinnitus in patients with bilateral subjective tinnitus. METHODS: Total number of 50 participants, 20 men, and 30 women were included in the research. Demographic data, data on hearing impairment obtained by tone audiometry, and data on difficulties caused by tinnitus obtained in two questionnaires - Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI) were used. RESULTS: Age above 30 years is significantly associated with tinnitus with hearing loss. Hearing impairment is also significantly more often associated with an auditory TFI index >6.7, a total THI index >20, and an emotional THI index >3. Hearing loss was noted in 76% of patients. CONCLUSION: Tinnitus represents a significant burden for patients, therefore it is important to assess the impact of tinnitus on daily activities and quality of life.

Troubleshooting Cochlear Implant Malfunction Using Neural Response Telemetry and Normal Saline.

Cochlear implantation has become a standard of care for a child diagnosed with bilateral profound sensorineural hearing loss with a structured surgical standard operating procedure. A 3-year-old boy with bilateral profound prelingual sensorineural deafness underwent a Med-EL Sonata Ti100 implant. We faced a peculiar situation intraoperatively after inserting the electrodes and closing the wound. The impedance recording indicated high ground path impedance with short-circuiting of few electrodes. As a bionic implant, its electronic components may at times malfunction both intraoperatively and/or postoperatively; therefore, neural response telemetry (NRT) was invented to check it. By using NRT and a few milliliters of normal saline, we were able to diagnose as well as rectify the malfunctioning of the implant.

Efficacy of vestibular rehabilitation program in children with balance disorders and sensorineural hearing loss.

OBJECTIVE: Asses the efficacy of a Vestibular-balance rehabilitation program to minimize or reverse balance disability in children with sensorineural hearing loss. METHOD: Forty-five hearing-impaired children with balance deficits (i.e., variable degrees of sensorineural hearing loss or auditory neuropathy). Thirty-five were rehabilitated with cochlear implants, and ten with hearing aids. Their age ranged from 4 to 10 years old. A Pre-rehab evaluation was done using questionnaires, neuromuscular evaluation, vestibular and balance office testing, and vestibular lab testing (using cVEMP and caloric test). Customized balances, as well as vestibular rehabilitation exercises, have been applied for three months. That was followed by post-rehab assessment, including the Arabic DHI questionnaire, PBS, BESS, HTT, and DVA test. RESULTS: There was a statistically significant difference in all measured parameters (including the Arabic DHI questionnaire, PBS, BESS, HTT, and DVA test) after rehabilitation. CONCLUSIONS: Vestibular-balance rehabilitation intervention positively impacts vestibular and balance functions in hearing-impaired children.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

L-shaped association of triglyceride glucose index and sensorineural hearing loss: results from a cross-sectional study and Mendelian randomization analysis.

Background: The association between the sensorineural hearing loss (SNHL) and triglyceride-glucose (TyG) index remains inadequately understood. This investigation seeks to elucidate the connection between the TyG index and SNHL. Methods: In this cross-sectional study, we utilized datasets sourced from the National Health and Nutrition Examination Survey (NHANES). A comprehensive analysis was conducted on 1,851 participants aged 20 to 69, utilizing complete audiometry data from the NHANES database spanning from 2007 to 2018. All enrolled participants had accessible hearing data, and the average thresholds were measured and calculated as both low-frequency pure-tone average and high-frequency pure-tone average. Sensorineural hearing loss (SNHL) was defined as an average pure tone of 20 dB or higher in at least one better ear. Our analysis involved the application of multivariate linear regression models to examine the linear relationship between the TyG index and SNHL. To delineate any non-linear associations, we utilized fitted smoothing curves and conducted threshold effect analysis. Furthermore, we conducted a two-sample Mendelian randomization (MR) study, leveraging genetic data from genome-wide association studies (GWAS) on circulating lipids, blood glucose, and SNHL. The primary analytical method for the MR study was the application of the inverse-variance-weighted (IVW) approach. Results: In our multivariate linear regression analysis, a substantial positive correlation emerged between the TyG index and SNHL [2.10 (1.80-2.44), p < 0.0001]. Furthermore, using a two-segment linear regression model, we found an L-shaped relationship between TyG index, fasting blood glucose and SNHL with an inflection point of 9.07 and 94 mg/dL, respectively. Specifically, TyG index [3.60, (1.42-9.14)] and blood glucose [1.01, (1.00-1.01)] concentration higher than the threshold values was positively associated with SNHL risk. Genetically determined triglyceride levels demonstrated a causal impact on SNHL (OR = 1.092, p = 8.006 × 10-4). In addition, blood glucose was found to have a protective effect on SNHL (OR = 0.886, p = 1.012 × 10-2). Conclusions: An L-shaped association was identified among the TyG index, fasting blood glucose, and SNHL in the American population. TyG index of more than 9.07 and blood glucose of more than 94 mg/dL were significantly and positively associated with SNHL risk, respectively.

Marked Underestimation of Platelet Count and a Characteristic Platelet Histogram as Clues to MYH9-Related Disorders.

BACKGROUND: The rapid development of automatic blood cell analyzers has greatly optimized complete blood count results. However, erroneous results relevant to automatic blood cell analyzers still exist. Pseudothrombocytopenia can be observed in both cases of anticoagulant-induced platelet aggregation, and the presence of large and giant platelets. METHODS: A rare case of a MYH9-related disorder, in which marked underestimation of platelet count was led by large and giant platelets using the impedance count by an automated hematology analyzer. Moreover, lancet-shaped and Dohle body-like cytoplasmic inclusions were detected in almost all white blood cells of the patient. RESULTS: The platelet count was done by an optical platelet counter or a fluorescence platelet counter, and peripheral blood smear was evaluated. In addition, the diagnosis of MYH9-related disorder was established by the molecular findings. CONCLUSIONS: Identification of the peripheral blood smear and familial history will eliminate the need for further laboratory testing and bone marrow examination.

Hearing Loss Among Families with 2 and More Affected Members in Golestan Province, Iran: A Cross-Sectional Study of 320 Families.

BACKGROUND: Our study centers on various aspects of families who have 2 or more members with hearing loss (HL) and are living in Golestan province in Iran. We aimed to identify those families with the highest probability of hereditary HL and also to examine the impact of consanguinity among them. METHODS: The families included in the study underwent a comprehensive screening process that involved their prenatal and postnatal histories as well as family medical histories. Additionally, each patient received a thorough clinical ear examination. The evaluation also took into account factors such as patterns of inheritance, consanguinity, a 3-generation pedigree, and physical examination. Following this initial assessment, patients were referred for a complete hearing evaluation, which included pure-tone audiometry, speech recognition threshold, otoacoustic emission, and auditory brainstem response tests. RESULTS: We identified a total of 8553 individuals living in Golestan province who are hearing impaired. Among those, our records indicate that 320 families had at least 2 affected members. The rate of consanguinity marriage in non-syndromic families was 64.43%. Also, a significant number (88.12%, or n=282) of the families exhibited hereditary HL, among which a substantial proportion (89.72%, or n=253) presented with nonsyndromic forms of HL. Furthermore, bilateral, stable, and prelingual HL were the most frequently observed types, and a majority of the patients were diagnosed with sensorineural and profound HL. CONCLUSION: This study revealed a correlation between consanguinity and the incidence of familial HL, with more probability of bilateral, prelingual, sensorineural, and profound forms.

Homozygous novel truncating variant of CLPP associated with severe Perrault syndrome.

A female proband and her affected niece are homozygous for a novel frameshift variant of CLPP. The proband was diagnosed with severe Perrault syndrome encompassing hearing loss, primary ovarian insufficiency, abnormal brain white matter and developmental delay.

Differences in semicircular canal function in the video head impulse test in patients in the chronic stage of sudden sensorineural hearing loss with vertigo and vestibular neuritis.

BACKGROUND: Sudden sensorineural hearing loss with vertigo (SHLV) and vestibular neuritis (VN) can result in prolonged dizziness. OBJECTIVES: This study aimed to compare the video head impulse test (vHIT) of patients with SHLV and VN. METHODS: Fifteen patients with SHLV and 21 patients with VN who visited the Vertigo/Dizziness Center of our hospital between December 2016 and February 2023 were included. vHIT was performed at the time of admission, and the VOR gain and catch up saccade (CUS) in the three types of semicircular canals (SCCs) were analyzed. RESULTS: Pathologic vHIT results were observed most frequently in the posterior SCC (73%), followed by lateral (53%) and anterior (13%) SCCs in the SHLV group. In contrast, pathologic vHIT results were observed most frequently in the lateral SCC (100%), followed by the anterior (43%) and posterior SCC (24%) SCCs in the VN group. Pathological vHIT results in the lateral and posterior SCC showed significant differences between the two groups, but for anterior SCC, no significant differences were found. CONCLUSIONS AND SIGNIFICANCE: Comparison of the two vHIT results revealed differences in the SCC dysfunction patterns. This may be due to the different pathophysiological mechanisms of the two vestibular disorders, which may result in prolonged vertigo.

[Role of intratympanic glucocorticoid treatment in sudden hearing loss]. / Stellenwert der intratympanalen Glukokortikoidtherapie in der Behandlung des Hörsturzes.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is one of the most common diseases in otolaryngology. Its etiology remains unknown. Furthermore, there is only a low level of evidence for the efficacy of established treatment modalities. In addition to systemic glucocorticoids, intratympanic corticosteroid treatment (ICT) has become increasingly important for treatment of ISSNHL. Different application strategies and treatment regimens have been described; however, uniform standards do not yet exist. ICT may be used for primary treatment as well as salvage therapy. Current data from meta-analyses show no benefit of intratympanic versus systemic primary therapy for sudden hearing loss (moderate evidence) but suggest a benefit of intratympanic secondary treatment over no treatment or placebo (high effect size, low evidence). Regarding combination of systemic and local glucocorticoid therapy in primary treatment of hearing loss, there may be a small benefit over systemic treatment alone (low effect size, low evidence).

An eight-year follow-up on auditory outcomes after neonatal hearing screening.

OBJECTIVE: The aim of this study is to assess the neonatal click Auditory Brainstem Response (ABR) results in relation to the subsequently determined mean hearing loss (HL) over 1, 2 and 4 kHz, as well as over 2 and 4 kHz. METHODS: Between 2004-2009, follow-up data were collected from Visual Reinforcement Audiometry (VRA) at 1 and 2 years and playaudiometry at 4 and 8 years of newborns who had failed neonatal hearing screening in the well-baby clinics and who had been referred to a single Speech and Hearing center. Hearing Level data were compared with ABR threshold-levels established during the first months of life. The Two One-Sided Tests equivalence procedure for paired means was applied, using a region of similarity equal to 10 dB. RESULTS: Initially, in 135 out of 172 children referred for diagnostic procedures hearing loss was confirmed in the neonatal period. In 106/135 of the HL children the eight-year follow-up was completed. Permanent conductive HL was established in 5/106 cases; the hearing thresholds were predominantly stable over time. Temporary conductive HL was found in 48/106 cases and the loss disappeared by 4 years of age at the latest. Sensorineural hearing loss (SNHL) was found in 53/106 cases, of which 13 were unilateral and 40 bilateral. ABR levels were equivalent (within a 10 dB range) to VRA levels at age 1 and 2 and play audiometry levels at age 4 and 8, both when VRA and play audiometry were averaged over both frequency ranges. CONCLUSION: Long term follow-up data of children with SNHL suggest that the initial click ABR level established in the first months of life, are equivalent to the hearing threshold measured at the age of 1, 2, 4 and 8 years for both mean frequency ranges. Click ABR can reliably be used as starting point for long-term hearing rehabilitation.