[Comparison of horizontal plane auditory spatial discrimination abilities and testing methods in patients with symmetrical sensorineural hearing loss].

Objective: To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration. Methods: A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson's correlation to assess the relationship between MAA and degree of hearing loss. Results: MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss (r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration (F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions: The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.

Identification of novel CDH23 variants linked to hearing loss in a Chinese family: A case report.

RATIONALE: Deafness is associated with both environmental and genetic factors, with hereditary deafness often caused by mutations in deafness-related genes. Identifying and analyzing deafness-related genes will aid in early diagnosis and pave the way for treating inherited deafness through gene therapy in the future. PATIENT CONCERNS: A 15-month-old girl underwent audiological examination at the outpatient clinic of the hospital due to hearing loss and her brother was diagnosed with profound bilateral sensorineural hearing loss at the age of 3. DIAGNOSES: The diagnosis was determined as extremely severe sensorineural hearing loss caused by genetic factors. INTERVENTIONS: Clinical data of the patient were collected, and peripheral blood samples were obtained from both the patient and her family members for DNA extraction and sequencing. OUTCOMES: By utilizing targeted capture next-generation sequencing to further screen for deafness-related genes, 2 novel variants in CDH23 were identified as the causative factors for the patient's deafness. LESSONS: This study identified 2 novel heterozygous mutations in a Chinese family. Both the proband and her sibling have non-syndromic hearing loss (NSHL) and carry distinct heterozygous mutations of cadherin-like 23 (CDH23). One mutation, CDH23:c.2651 A>G, originated from their mother and paternal family, affecting the exon23 domain of CDH23. The other mutation, CDH23:c.2113 G>T, was inherited from their paternal grandmother, impacting the exon19 domain of CDH23. These 2 novel mutations likely cause NSHL by affecting protein function. This finding suggests that identifying 2 novel mutations in CDH23 contributes to the genetic basis of NSHL.

Relating monaural and binaural measures of modulation sensitivity in listeners with and without hearing loss.

Listeners are sensitive to interaural time differences carried in the envelope of high-frequency sounds (ITDENV), but the salience of this cue depends on certain properties of the envelope and, in particular, on the presence/depth of amplitude modulation (AM) in the envelope. This study tested the hypothesis that individuals with sensorineural hearing loss, who show enhanced sensitivity to AM under certain conditions, would also show superior ITDENV sensitivity under those conditions. The second hypothesis was that variations in ITDENV sensitivity across individuals can be related to variations in sensitivity to AM. To enable a direct comparison, a standard adaptive AM detection task was used along with a modified version of it designed to measure ITDENV sensitivity. The stimulus was a 4-kHz tone modulated at rates of 32, 64, or 128 Hz and presented at a 30 dB sensation level. Both tasks were attempted by 16 listeners with normal hearing and 16 listeners with hearing loss. Consistent with the hypotheses, AM and ITDENV thresholds were correlated and tended to be better in listeners with hearing loss. A control experiment emphasized that absolute level may be a consideration when interpreting the group effects.

Sudden Hearing Loss Waves: The Effect of COVID-19 Infection and Vaccination on the Inner Ear.

Sudden sensorineural hearing loss (SSNHL) has emerged as a potential complication of COVID-19 infection and vaccination. Various mechanisms by which the SARS-CoV-2 virus can cause hearing loss have been reported, including direct viral invasion, neuroinflammation, blood flow disturbances, and immune-mediated response. However, the temporal relationship between COVID-19 infection and SSNHL remains unclear, with mixed findings and conflicting results reported in different studies. Similarly, while anecdotal reports have linked COVID-19 vaccination to SSNHL, evidence remains scarce. Establishing a correlation between COVID-19 vaccines and SSNHL implies a complex and multifactorial pathogenesis involving interactions between the immune system and the body's stress response. Nevertheless, it is important to consider the overwhelming evidence of the vaccines' safety and efficacy in limiting the spread of the disease and remains the primordial tool in reducing death.

Functional pathogenicity of ESRRB variant of uncertain significance contributes to hearing loss (DFNB35).

Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

Comparison Between the Veillon and the Symons-Fanning CT Classification Systems for Otosclerosis.

OBJECTIVE: To analyze the correlation between outcomes of stapes surgery and preoperative and postoperative audiometric results with different radiological staging classifications such as the Veillon classification (VC) and the Symons-Fanning classification (SFC). STUDY DESIGN: Retrospective observational study. SETTING: One tertiary hospital center. PATIENTS: Adult patients submitted to stapes surgery due to otosclerosis from January 2017 to December 2022. INTERVENTION: Evaluation of different radiological classifications such as the VC and SFC. MAIN OUTCOME MEASURES: Preoperative and postoperative pure-tone audiometric data, outcomes of stapes surgery success (closure of the ABG, rates of AC threshold less than or equal to 30 dB), and postoperative sensorineural hearing loss. RESULTS: A total of 87 patients and 97 operated ears were included. The SFC was associated with preoperative BC (p = 0.041) and AC (p = 0.018) and postoperative BC (p = 0.026) with an increase in thresholds with higher radiological stages. The VC was associated with postoperative AC (p = 0.045) with an increase in AC thresholds with increasing radiological stages. Lastly, both the VC (p = 0.032) and the SFC (p = 0.023) were associated with a decrease in rates of postoperative AC thresholds ≤30 dB with higher radiological stages. CONCLUSIONS: The SFC seems to be more useful to predict preoperative AC and BC and postoperative BC. On the contrary, the VC was more useful to predict postoperative AC. Both scales were similarly associated with the rate of AC thresholds ≤30 dB.

Correlation of Endolysmphatic Duct Signal Intensity With Clinical Features in Otological Diseases.

OBJECTIVE: Bilateral high signal intensity (SI) in the endolymphatic duct (ED) on magnetic resonance imaging (MRI) has been reported as a common characteristic in ears with large vestibular aqueduct syndrome (LVAS). However, the significance of bilateral high SI in the ED remains unknown. The present study aimed to compare the correlation between SI in the ED and the clinical manifestations in various otological disorders and consider the significance of the MRI findings. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: The study included 2,450 ears from 1,225 patients with various otological disorders. INTERVENTION: All ears underwent 3T enhanced MRI and were evaluated for the degree of endolymphatic hydrops (EH) and the SI ratios (SIRs; i.e., the calculation between SIs in the ED and those in the cerebellum). MAIN OUTCOME MEASURE: The imaging findings were compared with their clinical symptoms. RESULTS: Ears with bilateral high SIRs in the ED tended to have considerably less occurrence of EH in both the cochlea and vestibule than those with bilateral low SIRs. Ears with SIR ≥8 showed significantly elevated hearing thresholds at lower frequencies on pure-tone audiometry, although they exhibited a markedly lower incidence of cochlear EH than those with SIR <8. Moreover, ears with vertigo exhibited notably higher SIRs than those without vertigo. CONCLUSION: Bilateral high SI in the ED on MRI may reflect pathophysiology underlying sensorineural hearing loss and vestibular symptoms, which are not associated with EH formation.

Newborn hearing screening in Eastern Saudi Arabia: A tertiary hospital experience.

OBJECTIVES: To analyze the performance of a leading institution in implementing newborn hearing screening and address two key areas: the knowledge gap in screening practice and the prevalence of permanent sensorineural hearing loss in Saudi Arabia. METHODS: We analyzed the prevalence of hearing impairment in all live births at King Fahad Hospital of the University, Al Khobar, Saudi Arabia, from September 2018 to June 2022. Automated auditory brainstem response was used for both initial screening and rescreening. Newborns who failed the rescreening underwent a diagnostic evaluation. We assessed the coverage of initial screening, the rate of lost follow-up, referrals for rescreening and diagnostic evaluation, and the prevalence of hearing impairment. RESULTS: A total of 5,986 newborns were born. Of these, 96.5% were screened. The passing rate for the initial screening and rescreening was 71.8%. However, 27.5% of newborns were lost to follow-up. Only 0.7% required referral for a diagnostic evaluation. The overall prevalence of hearing impairment was 2.6 per 1,000 newborns. CONCLUSION: Early identification of hearing loss through newborn screening improves the lives of affected individuals. Our program currently meets the World Health Organization's 1-3-6 benchmark goals. However, the underestimation of permanent hearing loss due to the 30% lost-to-follow-up rate is a limitation. Emphasizing the importance of the screening program is crucial to raising awareness and improving the accuracy of prevalence rates.

[Assessment of the risk of hearing loss in children with cystic fibrosis]. / Otsenka riska patologii slukha pri mukovistsidoze u detei.

BACKGROUND: Cystic fibrosis (CF) is a severe hereditary disease with a multisystem lesion. Manifestations of CF include severe infectious purulent lesions of all parts of the respiratory tract, including purulent rhinosinusitis with nasal polyps. The involvement of the sinonasal region and the need for systemic use of ototoxic drugs (primarily aminoglycosides to treat resistant bacterial infection) potentially create a risk of both conductive and sensorineural hearing loss (SNHL). The available data on the epidemiology of hearing disorders in CF is contradictory. Currently, genetic determinants of the development of aminoglycoside SNHL have been identified. MATERIAL AND METHODS: For 136 CF patients (75 girls, 61 boys) aged 3 to 17 (9.4±3.9) years were performed audiological examination: tympanometry, transient-evoked otoacoustic emission and the pure tone threshold audiometry (standard frequency range) (n=126). History of systemic therapy with aminoglycosides was evaluated for each patient. Sequencing of c.35delG mutations in the GJB2 gene (nuclear DNA) and A1555G in the 12S rRNA gene (mitochondrial DNA) was performed in 215 patients with cystic fibrosis (the group partially overlaps with the audiological group), and as a control - 106 children with bronchial asthma and 103 healthy children, their age ranged from 3 to 17 (8.8±3.8) years. RESULTS: Audiological examination of CF children reveled a prevalence of conductive hearing loss comparable to the general population (2.4%). The frequency of SNHL was 1.6%, wich exceeds that of non-CF children. A genetic study revealed one case of heterozygous carriage of the c.35delG mutation in the GJB2 gene in a patient with bronchial asthma. In the group of patients with CF (n=215), mutations in the connexin 26 gene were not detected. No A1555G mutation was detected either in the group of patients with CF or in the control groups. CONCLUSIONS: Children with CF are at risk for the development of sensorineural, but not conductive hearing loss. Routine total screening for A1555G and c.35delG mutations probably seems not to be recommended.

[Pediatric sensorineural hearing loss related COVID-19. Clinical cases]. / Sensonevral'naya tugoukhost' v detskom vozraste, assotsiirovannaya s COVID-19. Klinicheskie nablyudeniya.

COVID-19 is an acute respiratory coronavirus infection in 2019 caused by the SARS-CoV-2 virus. Currently, the number of neurological complications in the acute or delayed period of coronavirus disease is increasing, including peripheral disorders of the auditory analyzer. OBJECTIVE: To present clinical cases of sensorineural hearing loss in children under 5 years of age after a novel coronavirus infection. MATERIAL AND METHODS: We report 3 cases of unilateral and 1 case of bilateral acquired deep sensorineural hearing loss, while the association with SARS-CoV-2 has been confirmed anamnetically and/or laboratory. RESULTS: The SARS-CoV-2 virus can have a depressing effect on the cochlea on its own or enhance the toxic effect of viruses during the recovery period after COVID-19. The true frequency of acute sensorineural hearing loss of infectious origin in childhood and, as its outcome, the formation of persistent hearing impairment has not been determined. CONCLUSION: Viruses are volatile, contagious, and clinically dangerous due to their complications. Vaccination is the most effective measure for the prevention of infectious diseases.

Audiological profile of patients with type 2 diabetes mellitus.

BACKGROUND:  South Africa shows a high prevalence of type 2 diabetes with reported association with auditory dysfunction. OBJECTIVES:  To describe the audiological profile of adults with this metabolic condition. METHOD:  Employing a descriptive research design, 35 individuals with type 2 diabetes, selected through purposive sampling, underwent a basic audiological assessment in addition to extended high-frequency (EHF) audiometry, distortion product otoacoustic emissions (DPOAE) testing and neurological auditory brainstem response (ABR) test. RESULTS:  This study revealed a 31.4% prevalence of hearing loss with 81.8% being sensorineural in nature. Poor hearing thresholds were observed at 16 kHz (n = 19; 54.3%), 18 kHz (n = 24; 68.6%) and 20 kHz (n = 30; 85.7%) in the right ear and at 16 kHz (n = 20; 57.1%), 18 kHz (n = 24; 68.6%) and 20 kHz (n = 30; 85.7%) in the left ear. Absent DPOAEs were observed at 6 kHz (n = 20; 51.7%) and 8 kHz (n = 24; 68.6%) in the right ear and at 6 kHz (n = 17; 48.6%) and 8 kHz (n = 29; 82.9%) in the left ear, possibly indicating that type 2 diabetes specifically targets higher frequency hearing. The ABR results revealed a delayed absolute latency of wave III bilaterally (right ear -69%; left ear - 51%), suggesting an impact of this metabolic disease on retro-cochlear pathways. CONCLUSION:  Hearing loss should be recognised as a comorbidity accompanying type 2 diabetes, which indicates the need for routine comprehensive audiological assessments to facilitate early detection and intervention.Contribution: The present findings have implications for audiology clinical protocols; diabetes related health policies and patient education.

[Analysis of clinical characteristics and curative effects of 169 patients with bilateral sudden sensorineural hearing loss].

Objective: To analyze the clinical characteristics, curative effect related factors and follow-up situation of bilateral sudden sensorineural hearing loss (BSSHL). Methods: The clinical data of 169 patients(338 ears) with BSSHL were retrospectively summarized, and the demographic characteristics, predisposing factors, concomitant symptoms and diseases, and audiological characteristics were statistically described. Additionally, influencing factors of curative effect and prognosis were statistically analyzed. Results: Among the 169 patients, 50.9% (86/169) of patients had at least one incentive, with cold and fatigue being the most common incentives(both 23/169). There were high rates of accompanying symptoms including tinnitus (150/169, 88.8%) and dizziness (100/169, 59.2%). Hypertension(49/169, 29.0%)and diabetes(23/169, 13.6%)were the most common concomitant diseases observed. Most cases exhibited all frequencies involvement, with flat type and total deafness type accounting for 83.1%(281/338 ears). The most common degree of hearing loss was total deafness(86/338 ears), with approximately 60.1%(203/338 ears) of the cases being severe or worse. The total effective rate of treatment was only 29.0%, but it increased to 39.5% for patients with course of disease≤14 days, however, when course of disease>30 days, the effective rate decreased sharply to 3.6%, showing a significant difference between these two groups(χ2=13.776,<0.01). Different types of hearing curves showed statistically significant difference in efficiency(χ2=14.782, P<0.01). Comparing the hearing improvements of 28 BSSHL patients from admission to discharge and from discharge to follow-up, it was found that the hearing improvement of the two groups showed statistically significant difference at the frequencies of L-250 Hz, L-500 Hz, R-125 Hz, R-250 Hz and R-500 Hz(Z value was -2.495, -3.083, -3.970, -3.388 and -3.264 respectively, all P<0.05). The proportion of patients with elevated serum IgE was much higher than that of the normal population. Conclusion: BSSHL patients suffer from serious hearing loss, and many also experience tinnitus and vertigo symptoms. Due to the poor efficiency of treatment, it is better for patients to be treated within 30 days of onset. For patients of hearing loss in the low frequency range, hearing improvement is more significant during hospitalization. And the occurrence of BSSHL may involve an immune mechanism.

Mangiferin alleviates cisplatin-induced ototoxicity in sensorineural hearing loss.

Mangiferin(MGF) exhibits crucial biological roles, including antioxidant and anti-inflammatory functions. However, how to clearly elucidate the functioning mechanism of MGF for inhibiting cisplatin-induced hearing loss requires in-depth investigation. In this work, we aimed at gaining insight into how MGF functions as the protective agent against cisplatin-triggered ototoxicity using various assays. The variation for reactive oxygen species (ROS) concentrations was determined with MitoSOX-Red and 2',7'-Dichlorodihydrofluorescein diacetate staining (DCFH-DA). The protective function and corresponding mechanism of MGF in hair cell survival in the House Ear Institute-Organ of Corti (HEI-OC1) cell line were assessed using RNA sequencing (RNA-Seq). Our findings demonstrated that MGF significantly alleviated cisplatin-induced injury to hair cells in vitro, encompassing cell lines and cochlear explants, as well as in vivo models, including C57BL/6 J mice and zebrafish larvae. Mechanistic studies revealed that MGF reversed the increased accumulation of ROS and inhibited cell apoptosis through mitochondrial-mediated intrinsic pathway. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting data indicated MGF protected against cisplatin-mediated ototoxicity via the mitogen-activated protein kinase pathway (MAPK). These findings demonstrated MGF has significant potential promise in combating cisplatin-induced ototoxicity, offering a foundation for expanded investigation into therapeutic approaches for auditory protection.

Peripheral and brainstem auditory evaluation in post-COVID-19 individuals.

PURPOSE: The purpose of this study was to investigate the peripheral and central auditory pathways in adult individuals after COVID-19 infection. METHOD: A total of 44 individuals aged between 19 and 58 years, of both genders, post-COVID-19 infection, confirmed by serological tests, with no previous hearing complaints and no risk factors for hearing loss, were assessed. All the participants underwent the following procedures: pure tone audiometry, logoaudiometry, immitanciometry, and Brainstem Auditory Evoked Potentials (BAEP), in addition to answering a questionnaire about auditory symptoms. RESULTS: Thirteen individuals (29.5 %) had some hearing threshold impairment, mainly sensorineural hearing loss. In the BAEP, 18 individuals (40.9 %) presented longer latencies, mainly in waves III and V. According to the questionnaire answers, 3 individuals (9.1 %) reported worsened hearing and 7 (15.9 %) tinnitus that emerged after the infection. As for the use of ototoxic drugs during treatment, 7 individuals (15.9 %) reported their use, of which 5 showed abnormalities in peripheral and/or central auditory assessments. CONCLUSION: Considering the self-reported hearing complaints after COVID-19 infection and the high rate of abnormalities found in both peripheral and central audiological assessments, it is suggested that the new COVID-19 may compromise the auditory system. Due to the many variables involved in this study, the results should be considered with caution. However, it is essential that audiological evaluations are carried out on post-COVID-19 patients in order to assess the effects of the infection in the short, medium, and long term. Future longitudinal investigations are important for a better understanding of the auditory consequences of COVID-19.

Auditory Phenotype of a Novel Missense Variant in the CEACAM16 Gene in a Large Russian Family With Autosomal Dominant Nonsyndromic Hearing Loss.

Autosomal dominant hearing loss is represented by a large number of genetically determined forms. Over 50 genes associated with dominant nonsyndromic hearing impairments were described. Pathogenic variants in the CEACAM16 gene lead to the development of DFNA4B hearing loss. Currently, 8 pathogenic variants in this gene have been described. The objective of this study was to study the audiological and molecular genetic characteristics of a large family with CEACAM16-associated autosomal dominant nonsyndromic hearing loss. A detailed anamnesis was collected, and a comprehensive audiological examination was performed for 21 family members. Genetic testing was performed, including whole-genome sequencing for the proband's son and Sanger sequence analysis for the proband and for all available family members. In a large Russian family, including 5 generations, an autosomal dominant type of slowly progressing nonsyndromic late-onset hearing loss was observed. Eleven family members suffer from hearing impairment, which starts with tinnitus and threshold increase at high frequencies, since the age of 5-20 years. Hearing loss slowly progresses with age in each person and is similar to age-related hearing loss. We have detected the novel likely pathogenic variant с.419С>T (p.(Thr140Ile)) in exon 3 of the CEACAM16 gene, which segregates with late-onset nonsyndromic hearing loss in this family. The clinical data obtained in the examined family correspond with the phenotype in previously described cases. In general, the study widened the mutation spectrum of the gene, allowing to carry out medical genetic counseling and to answer the questions about the hearing impairment prognosis for future generations.

Association of Metabolic Syndrome or Weather Conditions with the Severity and Prognosis of Sudden Sensorineural Hearing Loss.

It is reported that sudden sensorineural hearing loss (SSNHL) is closely related to diabetes, hypertension, and hyperlipidemia. While the metabolic syndrome (MetS) is a multifactorial disease that includes diabetes, hypertension, dyslipidemia, and obesity, which are known to be associated with SSNHL. Weather conditions have long been known to affect the SSNHL. This study aimed to make a clear connection between MetS, or weather conditions, and the severity and prognosis of SSNHL. 127 SSNHL patients have been divided into the MetS group and the non-MetS group, and the demographic and clinical characteristics of the 2 groups have been analyzed retrospectively. There were 52 (40.9%) patients in the MetS group, while there were 75 (59.1%) patients in the non-MetS group. The rate of vertigo, hypertension, diabetes, lower high-density lipoprotein cholesterol (HDL-C) levels, high triglyceride (TG), and body mass index (BMI) ≥25 (kg/m2 ) were significantly higher in the MetS group than those in non-MetS group. Vertigo, hypertension, and Mets were linked to the severity of hearing loss. The rate of complete recovery and partial recovery in the MetS group was clearly lower than that in non-MetS group. According to the multivariate analysis, MetS was significantly associated with a poorer prognosis of SSNHL; a high ambient temperature difference at onset and hypertension were correlated with a poor prognosis. These results demonstrate that the severity and prognosis of SSNHL can be influenced by the MetS. High ambient temperature differences at onset and hypertension were indicators of a poor prognosis for SSNHL.

Postoperative Late Hearing Deterioration in Cholesteatoma with Labyrinthine Fistulas.

A labyrinthine fistula is a severe complication of middle ear cholesteatoma that can cause profound sensorineural hearing loss and vertigo. However, there is no consensus regarding the transition to postoperative hearing. Although hearing deteriorates gradually with a delay in some cases of labyrinthine fistula, insufficient consideration has been given to this point. We examined perioperative changes in cases of middle ear cholesteatoma with labyrinthine fistulas. We retrospectively reviewed the medical records of 578 patients with middle ear cholesteatoma who underwent tympanoplasty at our hospital between 2016 and 2021. Patients with labyrinthine fistulas were selected; their perioperative bone-conduction hearing was assessed. Fistula depth was determined following the classification reported by Dornhoffer et al. The hearing was compared preoperatively, early postoperatively (3-6 months), and 1 year postoperatively. Forty-eight patients (8.3%) had labyrinthine fistulas. Regarding depth, 21 cases were type I, 14 were type IIa, 3 were type IIb, and 10 were type III. Preoperative bone-conduction hearing was significantly poor in invasion type IIb or deeper cases. Cases with type IIb or deeper fistulas, multiple fistulas, or vertigo deteriorated postoperatively. Type III cases or those with multiple fistulas deteriorated further from the early postoperative period to 1 year postoperatively. Concerning frequency, 500 and 2000 Hz showed a delayed deterioration. This is a valuable report of delayed hearing loss after surgery in patients with a labyrinthine fistula. This change is associated with the labyrinthine fistula's depth and multiple fistulas-this is important during preoperative counseling of patients undergoing surgery.

Heterozygous variants in transmembrane channel-like 1 gene cause autosomal recessive nonsyndromic hearing loss.

Autosomal recessive non-syndromic hearing loss (ARNSHL) can cause severe or very severe pre-speech hearing loss. Transmembrane channel-like 1 (TMC1) gene is the sixth deafness gene discovered, but the precise extent of its protein structure and function is unknown. First, history collection, audiology examination and imaging examination were performed on the proband and his family members. Peripheral blood of proband and family members was collected, genomic DNA was extracted, exon high-throughput sequencing technology was used to detect the deafness gene mutation of the proband, and Sanger sequencing was performed to verify the TMC1 gene of the proband's parents. The proband was born with hearing impairment, normal tympanic function, inability to induce acoustic reflex in both ears (acoustic reflex threshold is 100 dBHL), and severe sensorineural deafness. One of his sisters has severe sensorineural hearing loss, and neither his parents nor his other sister is hearing impaired. High-throughput sequencing of the proband identified mutations at c.741+3_741+6delAAGT (splicing) and c.884C>T (p.A295V) of the TMC1 gene, two of which were heterozygous mutations. Sanger sequencing confirmed that the c.884C > T mutation was inherited from the mother, while the c.741+3_741+6delAAGT mutation was derived from the father. Prediction of amino acid function suggested that both mutations were pathogenic mutations. In conclusion, we found a new pathogenic complex heterozygous mutation of the TMC1 gene, which enriched the mutation spectrum of the TMC1 gene and provided a basis for genetic counseling and prenatal diagnosis of ARNSHL.

H Syndrome: Three New Cases from Morocco.

A 19-year-old girl presented with symmetric and bilateral hyperpigmentation, an indurated lesion that initially appeared on the axillary fold at the age of 14, which then extended to the lower back, anterior aspect of both thighs, and popliteal fold. No hypertrichosis was observed (Figure 1).The patient was the youngest of the four children, born from the first-degree consanguineous marriage. She was born at full term and weighed 2,420 g at birth. No similar patient was present in the family. The patient experienced delayed motor acquisition and stature growth (3rd percentile) until the age of 4. Right hypoacusis was diagnosed at the age of 6. She developed hallux valgus, flexion contracture of the fin-gers and toes, barrel deformity of the anterior thorax, and recurrent fever. The laboratory tests, including fasting blood glucose, -triglycerides, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were normal. Her abdominal, pelvic, and transthoracic ultrasound scans were normal, with no hepatosplenomegaly, lymphadenopathy, or cardiac abnormalities. Histologic analysis demonstrated patchy acanthosis of the epidermis, with orthokeratotic hyperkeratosis. Keratinocyte hyperpigmentation and spongiosis at certain areas were observed with moder-ate inflammation because of the infiltration of lymphocytes, histiocytes, and plasma cells. Immunohistochemical analysis showed macrosialin (CD68+) and common gamma chain (γc) CD132. Germline mutations in the SLC29A3 gene were not analyzed. The patient was prescribed dermocorticoids with depigmentation therapy, which demonstrated moderate clinical evolution.

Hearing instability and abnormal auditory pathways in infants with congenital cytomegalovirus infection: An audiological and radiological single-centre prospective cohort analysis.

INTRODUCTION: This prospective cohort study aims to investigate the hearing dynamics and the changes in the central auditory pathways in infants with congenital cytomegalovirus (cCMV) infection. MATERIALS AND METHODS: cCMV-infected neonates aged ≤3 weeks old were recruited and underwent clinical and laboratory tests to detect viremia and symptomatic infection, hearing examinations at three and six months of age, and radiological imaging of brain auditory pathways using diffusion tensor imaging. RESULTS: From 26 eligible infants (52 ears), we detected symptomatic infection in nine (34.6%), viremia in 14 (14/25; 56.0%) and sensorineural hearing loss (SNHL) in 14 infants (53.8%). We observed 40 ears (76.9%) with unstable hearing thresholds, 17 (42.5%) of which fluctuated. Hearing fluctuation and progressivity were more common in symptomatic infection (66.7% vs. 14.7%, p<0.001; and 38.9% vs. 2.9%, p=0.002; respectively). A substantial proportion of ears had reduced fractional anisotropy (FA) in the medial geniculate body (59.1%), superior olivary nucleus (45.5%), trapezoid body (40.9%), auditory radiation (36.4%) and inferior colliculus (31.8%). Symptomatic infection was associated with an increased FA in the medial geniculate body (mean difference, MD: 0.12; 95% Confidence Intervals, 95%CI: 0.03, 0.22) and viremia in the inferior colliculus (MD: 0.09; 95%CI: 0.02, 0.16). An FA in the inferior colliculus of ≥0.404 had a sensitivity and specificity of 68.8% and 83.3% in predicting viremia (area under the curve 0.823; 95%CI: 0.633, 1.000, p=0.022). CONCLUSION: SNHL along with its fluctuation and progression are common in cCMV-infected infants. cCMV infection may induce structural changes in the central auditory pathway.