Search Results (609)

Persistent microscopic hematuria in children is often considered benign, yet recent evidence shows that a substantial proportion of affected individuals have underlying glomerular disease, particularly collagen IV-related nephropathies. We report a case of autosomal dominant Alport syndrome (ADAS) diagnosed just before discontinuation of long-term follow-up in a young woman initially presumed to have benign familial hematuria. The proband had persistent microscopic hematuria from early childhood, with normal renal function and no extrarenal manifestations. Her mother also had microscopic hematuria without kidney impairment, and the absence of accessible family history reinforced the assumption of benign familial hematuria. At age 42, the mother developed sensorineural hearing loss, and around the same time, the family learned that the maternal grandfather was undergoing dialysis for end-stage renal disease of unknown etiology. These findings prompted genetic testing, which identified a heterozygous pathogenic COL4A4 frameshift variant (c.2317_2318del; p.Arg773GlyfsTer14) in both the mother and the proband, confirming ADAS. This case illustrates the phenotypic variability of ADAS within a single family and highlights the limitations of relying solely on clinical features or incomplete family history. In contemporary practice, persistent glomerular hematuria warrants long-term follow-up and a low threshold for molecular testing of COL4A3-COL4A5, even in the absence of overt clinical signs. Earlier genetic evaluation would likely have enabled a timelier diagnosis in this case. This report underscores the importance of reassessing presumed benign hematuria and integrating genetic testing into the diagnostic approach for children and young adults with persistent microscopic hematuria. Full article

Hereditary sensorineural hearing loss (SNHL) represents a significant global public health burden. DFNX2, an X-linked form of non-syndromic SNHL, is caused by pathogenic variants in the POU3F4 gene. This study aimed to identify a novel POU3F4 mutation and characterize its functional consequences to elucidate the molecular pathogenesis of DFNX2. A three-generation Chinese family with X-linked deafness was recruited. Targeted next-generation sequencing was used to screen candidate variants, which were validated by Sanger sequencing for co-segregation analysis. Functional assays, including subcellular localization, dual-luciferase reporter assay, Western blotting, and homology modeling, were performed to assess the mutation’s effects. A novel frameshift mutation, c.670_673dupGGTA (p.(Asn225Argfs*2)), was identified and showed complete co-segregation with the deafness phenotype. The mutant protein exhibited cytoplasmic mislocalization, and dual-luciferase assays revealed a severe reduction in transcriptional activation capacity, whereas Western blot confirmed stable expression of the truncated protein. Structural modeling predicted the loss of both the POUS and POUH DNA-binding subdomains. Collectively, this study expands the mutational spectrum of POU3F4 and supports previously reported mechanisms underlying DFNX2 pathogenesis. Full article

Objectives: To characterize heterozygous pathogenic COCH variants in a French cohort with non-syndromic sensorineural hearing loss (NSHL) and assess genotype–phenotype correlations in autosomal dominant NSHL (DFNA9). Setting: National Reference Center for Genetic Hearing Loss, Necker–Enfants Malades Hospital, Paris, France. Methods: This retrospective observational study included 69 individuals from 20 unrelated families diagnosed with DFNA9 (2005–2025). All individuals underwent clinical and audiological evaluations and genetic testing via targeted COCH Sanger sequencing or next-generation sequencing (NGS) panels. Variants were interpreted according to ACMG guidelines. Audiometric profiles and vestibular data were collected. Results: Seven known pathogenic COCH variants were found in ten families, and ten novel likely pathogenic variants in the others. Variants in vWFA domains were associated with early or late onset, progressive, bilateral and symmetrical hearing loss. Three variants (p.Gln410Arg, p.Ile450Val, p.Cys542Arg) were associated with congenital or prelingual onset, an atypical DFNA9 presentation. Variants in the LCCL domain were associated with later-onset hearing loss and more frequent vestibular dysfunction. Vestibular abnormalities were observed in about half of early-onset cases. Conclusions:COCH-related hearing loss is a rare cause of autosomal dominant NSHL, with only 20 families identified over two decades within the French network. This study expands the mutational spectrum of COCH by reporting ten novel variants and supports a domain-specific genotype–phenotype correlation. These findings improve the understanding of DFNA9 variability and have direct implications for clinical diagnosis, prognosis, and genetic counseling. Full article

Background/Objectives: Ménière’s disease (MD) is a chronic inner-ear disorder characterized by vertigo, tinnitus, and fluctuating sensorineural hearing loss (SNHL) that impairs health-related quality of life (HRQoL) and is frequently accompanied by psychological distress. This study aims to quantify psychological distress and generic HRQoL in patients with definite MD compared with age- and sex-matched general-population controls and to examine the associations between hearing loss (HL) severity, symptom-related handicap, and these outcomes within the MD cohort. Methods: In this observational cross-sectional study, 45 adults with definite MD were recruited from an otolaryngology clinic in Portugal and individually matched (1:3) by sex and 10-year age strata to 135 participants from the EpiDoC population cohort. HRQoL was assessed using the SF-36v2 and EQ-5D-3L, psychological distress using the HADS, and tinnitus- and dizziness-related handicap using the THI and DHI. HL severity was staged using the AAO-HNS (1995) criteria. Results: Patients with MD had higher anxiety and depression scores and nearly twice the prevalence of abnormal anxiety compared with controls. SF-36v2 scores were significantly worse in several role and psychosocial domains, with less bodily pain but similar physical functioning and general health. EQ-5D-3L revealed a lower utility index and higher pain/discomfort and anxiety/depression. Within the MD cohort, HL stage was only weakly related to distress and HRQoL. In contrast, higher THI and DHI scores were consistently associated with more severe anxiety and depression and lower SF-36v2 scores. In multivariable analysis, abnormal anxiety was strongly associated with moderate-to-severe tinnitus handicap (OR = 17.5), whereas higher depressive symptoms independently predicted moderate-to-severe dizziness handicap, with abnormal anxiety showing a strong but borderline association with the latter. Conclusions: MD confers clinically meaningful HRQoL decrements and a higher psychological distress burden than in the general population. Tinnitus- and dizziness-related handicap and psychological distress, particularly anxiety, rather than HL severity, are key multidisciplinary management targets. Systematic screening for anxiety and depression, regardless of audiometric stage, should be integrated into MD care pathways. Full article

Background/Objectives: Diving exposure can cause auditory injury involving both the middle and inner ear structures. Inner ear barotrauma (IEB) and inner ear decompression sickness (IEDCS) are the major inner ear disorders and frequently present with auditory and vestibular symptoms. This study examined how diving characteristics relate to patterns of auditory trauma. Methods: A retrospective chart review of 30 patients, with 36 affected ears, was performed. Diving depth, clinical manifestations, and treatment responses were analyzed to identify factors influencing related prognosis. Results: Diving depth was an important factor associated with symptom severity and the type of injury. Dives deeper than 30 m of seawater were linked to a higher incidence of sudden sensorineural hearing loss and vertigo. In contrast, transient symptoms with minimal objective abnormalities were typically observed in shallow dives. Patients with concomitant decompression sickness (DCS) showed poorer auditory and vestibular recovery following hyperbaric oxygen therapy, while those without DCS showed better hearing improvement. Vertigo was observed in 80% of IEB cases and 66.7% of IEDCS cases. Hearing recovery appeared to be more frequently observed in cases presenting with middle ear symptoms, suggesting a relatively favorable prognosis for IEB compared with IEDCS. Conclusions: The findings suggest potential associations between diving depth and DCS, and its involvement may play a role in the severity and prognosis of diving-related inner ear injury. IEB appeared to be associated with more favorable auditory outcomes compared with IEDCS; however, this observation should be interpreted with caution due to potential diagnostic uncertainty. Given the descriptive nature of the study, further studies with larger cohorts are needed to refine prognostic indicators and optimize management strategies. Full article

Cisplatin-induced ototoxicity is a permanent, bilateral sensorineural hearing loss occurring in up to 80% of treated patients. Its defining and clinically challenging feature is the progressive worsening of auditory function that continues well after chemotherapy has ended, a trajectory that cannot be explained by cumulative dose alone. This article is a comprehensive review of the present research studies on mechanisms that are responsible for this post-treatment progression. The cochlea, unlike other organs, appears to be unable to eliminate platinum (the active divalent metal ion released from cisplatin and responsible for its cytotoxic and ototoxic effects): traces of it can be found in human temporal bone tissue even more than 18 months after last infusion, and bone might serve as a long-term systemic reservoir. Within the inner ear, platinum accumulates preferentially in the stria vascularis, impairing endocochlear potential and outer hair cell function. Retained platinum sustains cascading effects including sustained NOX3-dependent oxidative stress, mitochondrial dysfunction, ongoing genotoxic injury to non-regenerative cells, and the early loss of ribbon synapses that precipitates delayed spiral ganglion neurodegeneration. Pharmacogenetic variability in platinum transport and antioxidant metabolism further modulates individual susceptibility. These findings support lifelong audiological surveillance and provide a basis for designing strategies that can protect hearing without compromising the essential anticancer efficacy of cisplatin therapy. Full article

Background: Sensorineural hearing loss represents a significant global health burden affecting over 1.5 billion individuals worldwide. Modern hearing aids, equipped with digital signal processing and smart connectivity features, constitute a cornerstone of neuro-sensory rehabilitation. However, the psychosocial impact of these assistive smart technologies on patient self-esteem remains incompletely characterized. Methods: A cross-sectional multivariate study was conducted with 245 participants, divided into three groups: normal-hearing controls (NH, n = 73), hearing-impaired patients using smart hearing aid technology (HA users, n = 86), and hearing-impaired patients not using hearing aid technology (HA non-users, n = 86). Self-esteem was measured using the Rosenberg Self-Esteem Scale (SES). Hearing disability and tinnitus severity were assessed with the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Handicap Inventory (THI), respectively. Data analysis included one-way ANOVA, Tukey’s HSD post hoc tests, Pearson correlations, and multivariate regression. Results: Hearing aid users showed significantly higher SES scores (35.41 ± 5.32) compared to non-users (22.99 ± 4.53; p < 0.001, Cohen’s d = 2.515). One-way ANOVA indicated highly significant differences among groups (F = 299.00, p < 0.001, η² = 0.712). SES was negatively correlated with HHIA (r = −0.573, p < 0.001) and THI (r = −0.443, p < 0.001), while HHIA and THI were strongly positively correlated (r = 0.729, p < 0.001). In multivariate analysis, HA use remained a strong independent predictor of self-esteem (β ≈ 11.9, p < 0.001), even after adjustment for age, sex, HHIA, and THI. Perceived hearing handicap was independently associated with lower self-esteem, whereas tinnitus severity was not a significant predictor in the fully adjusted model. The model explained approximately 65% of the variance in self-esteem scores. Conclusions: Smart hearing-aid use is strongly and independently associated with higher self-esteem in patients with sensorineural hearing loss. These results support the inclusion of modern audiological rehabilitation devices in comprehensive management strategies for long-term conditions and highlight psychosocial benefits that extend beyond hearing restoration. Full article

Background/Objectives: Spectral resolution is strongly associated with speech perception for adult cochlear implant users, but the developmental trajectory of spectral resolution in childhood is more complex and far less understood. Music-based training presents a unique opportunity to address this gap, as musical stimuli feature spectral complexity and fine frequency cues which map to spectral resolution. This study explored if a 12-week music-based intervention could support better spectral resolution in children with cochlear implants. Methods: Twelve children with cochlear implants participated in this longitudinal, repeated-measures study. The music training intervention consisted of group-based in-person music therapy and a take-home music app. Participants (six boys, six girls; M age = 7.3 years) were pseudo-randomized into an immediate training group (n = 4) or delayed-start waitlisted group (n = 8). Inclusion criteria required bilateral moderate-to-profound sensorineural hearing loss, prelingual device fitting, and consistent bilateral device use. Eight children had bilateral CIs and four were bimodal listeners. Results: Spectral resolution perception was significantly enhanced after participating in the music intervention with a mean increase of 2 rpo, F(3, 10.7) = 3.859, p = 0.017. Previous engagement with music and age were not associated with spectral resolution. Conclusions: Despite the known limitations of CIs on spectral resolution, the results of this study indicate that music training can improve spectral resolution perception in children using CIs. Full article

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), represents a chronic immune-mediated disorder frequently associated with extraintestinal manifestations. While musculoskeletal, dermatologic, and ocular complications are well recognized, ear, nose, and throat (ENT) involvement remains underrecognized despite its potential morbidity. Objective: To systematically evaluate the spectrum of ENT manifestations in IBD, focusing on clinical presentation, diagnostic approaches, and outcomes. Methods: A systematic literature search was conducted in PubMed and Scopus in accordance with PRISMA 2020 guidelines. Eligible studies included English-language human studies (2015–2026) reporting ENT manifestations in UC or CD. Following screening, 23 studies were included in the qualitative synthesis. Extracted data comprised study design, IBD subtype, patient demographics, ENT manifestations, diagnostic methods, and clinical outcomes. Results: The majority of studies consisted of case reports and small observational series. Sensorineural hearing loss (SNHL) was the most frequently reported manifestation in both adult and pediatric populations, with evidence suggesting immune-mediated mechanisms and variable responsiveness to corticosteroids. Nasal involvement included pyoderma gangrenosum, pyoderma vegetans, and aseptic nasal septal abscess, occasionally resulting in severe structural complications such as saddle-nose deformity. Laryngeal and airway involvement included dysphonia, tracheitis, and rare but potentially life-threatening inflammatory airway disease. Additional findings included associations with chronic rhinosinusitis. Diagnosis relied on audiometry, imaging, endoscopy, and histopathology. Systemic corticosteroids were frequently effective; however, delayed recognition may lead to irreversible sequelae. Conclusions: ENT manifestations in IBD constitute a clinically heterogeneous but important group of extraintestinal complications. Increased awareness of ENT manifestations may support earlier diagnosis and multidisciplinary management of IBD, potentially reducing irreversible complications. Full article

Occupational noise-induced hearing loss (NIHL) is a common occupational disorder, yet non-invasive molecular indicators of chronic occupational noise exposure remain insufficiently characterized. Although the cochlear mechanisms behind NIHL have been extensively studied in experimental models, peripheral blood transcriptomic alterations in affected human populations are less well defined. In this exploratory study, we aimed to describe peripheral blood gene expression patterns associated with occupational NIHL and to generate candidate molecular signals for future validation. Peripheral blood RNA sequencing (RNA-seq) was performed in 11 male individuals with occupational bilateral sensorineural hearing loss and four noise-unexposed healthy male controls. Transcript abundance was quantified using a standardized RNA-seq workflow, and formal differential expression analysis was conducted on gene-level count data derived from Salmon quantification using DESeq2 with Benjamini–Hochberg correction. Through our analysis, we identified a limited set of differentially expressed genes, including upregulated interferon-associated transcripts, such as RSAD2, IFIT1, IFI44L, and CMPK2, host-defense-related genes, including DEFA1, DEFA3, and DEFA4, and immune-regulatory transcripts such as HLA-DRB1 and GPR15, together with downregulated non-coding RNAs including SNORD3A and SNORD3C. These findings suggest that occupational NIHL may be accompanied by detectable peripheral blood transcriptomic alterations, predominantly involving immune- and host-defense-related pathways. Given the limited cohort size and exploratory design, these genes represent preliminary candidates for validation in larger independent cohorts. Full article

Introduction: The present study aimed to compare cortical auditory maturation, as reflected by P1 latency of cortical auditory evoked potentials (CAEPs), in children with congenital severe-to-profound sensorineural hearing loss rehabilitated with unilateral cochlear implants (CIs) or bilateral conventional hearing aids (HAs). Materials and Methods: Eighty-five children with congenital severe-to-profound sensorineural hearing loss were included in this retrospective comparative study. Participants were divided into two groups: unilateral CI users (n = 42) and bilateral HA users (n = 43). All children were fitted with their devices before 48 months of age and achieved aided free-field thresholds between 30 and 50 dB HL. CAEPs were recorded using the Fonix^® HEARLab System with speech stimuli (/m/, /g/, /t/) presented at 55 dB SPL. P1 latency values were measured and compared between groups using independent samples t-tests. Correlation analyses were performed to assess the relationship between duration of device use and P1 latency. Results: Eighty-five children were included (CI: n = 42; HA: n = 43). Mean P1 latency values did not differ significantly between groups for the /m/ stimulus (126.4 ± 29.13 ms vs. 126.4 ± 29.28 ms, p = 1.00), /g/ stimulus (106.5 ± 26.46 ms vs. 110.1 ± 29.49 ms, p = 0.55), or /t/ stimulus (114.7 ± 22.93 ms vs. 118.5 ± 27.19 ms, p = 0.48). Age at device fitting was comparable between groups (27.95 ± 9.10 vs. 26.88 ± 14.15 months, p = 0.68). The duration of device use was significantly longer in the HA group (48.02 ± 28.39 months) compared to the CI group (26.00 ± 15.92 months) (p < 0.001). Correlation analysis revealed no significant association between duration of device use and P1 latency for any stimulus (/m/: p = 0.28; /g/: p = 0.17; /t/: p = 0.09). Conclusions: When devices were fitted before 48 months of age and aided thresholds were optimized, unilateral cochlear implantation and bilateral conventional hearing aids showed comparable P1 latency values as an index of cortical auditory maturation. These findings suggest that early and adequate auditory stimulation may play an important role in supporting cortical auditory development in children with congenital hearing loss, although results should be interpreted within the context of individualized clinical management. Full article

Background and Objectives: The inner ear has traditionally been regarded as an immunoprivileged and anatomically isolated organ. However, growing interest in neuro-lymphatic interactions has raised the hypothesis that glymphatic and lymphatic mechanisms may contribute to auditory pathology and its association with cognitive dysfunction. This systematic review aimed to synthesize current human evidence regarding anatomical, imaging, and clinical correlates of glymphatic mechanisms in the inner ear and audiological pathologies, and to quantitatively evaluate currently available biomarkers. Materials and Methods: A structured search of PubMed, Scopus, and Cochrane databases was performed from inception through March 2026. Eligible studies included human investigations reporting anatomical, histopathological, or MRI-based glymphatic assessments related to inner ear disorders. Risk of bias was assessed using the Newcastle–Ottawa Scale and Joanna Briggs Institute tools. Meta-analysis was conducted for diffusion tensor image analysis along the perivascular space (DTI-ALPS) indices comparing auditory disorders with healthy controls. Results: Six studies met inclusion criteria (five cross-sectional imaging studies and one surgical histopathological case series). Histopathology demonstrated lymphatic capillaries in advanced Ménière disease. MRI studies consistently reported reduced ALPS indices and/or increased choroid plexus volume and enlarged perivascular spaces in tinnitus, congenital sensorineural hearing loss, and age-related hearing loss. Meta-analysis of five studies showed a significant reduction of ALPS index in auditory disorders compared with controls (SMD = −0.73, 95% CI −0.90 to −0.55; p < 0.001), with no heterogeneity. Glymphatic markers were frequently associated with audiological data, cognitive performance and inflammatory biomarkers. Conclusions: Human evidence supports the presence of altered central glymphatic function across diverse auditory phenotypes. Although predominantly based on indirect MRI proxies and cross-sectional data, the meta-analytic findings strengthen the biological plausibility of an auditory–glymphatic interaction. Prospective longitudinal studies are warranted to clarify causality and therapeutic implications. Full article

Background/Objectives: The cochlea and vestibular organs develop concurrently during embryogenesis and share anatomical and functional pathways. As a result, congenital factors affecting the vestibulocochlear system may impair both hearing and vestibular function. Despite this, the relationship between congenital bilateral sensorineural hearing loss (SNHL) and vestibular dysfunction remains insufficiently defined. This study evaluated vestibular function in patients with congenital bilateral SNHL and investigated the association between hearing loss severity and vestibular function. Methods: A total of 202 participants aged 7–31 years were enrolled, including 102 patients with congenital bilateral SNHL and 100 healthy controls. Vestibular function was assessed using videonystagmography (VNG) during sinusoidal harmonic acceleration (SHA) rotational testing and caloric testing performed according to the Fitzgerald–Hallpike protocol, as well as with the video head impulse test (vHIT). Statistical analyses compared vestibular parameters between groups and assessed correlations with hearing loss severity. Results: Patients with congenital bilateral SNHL exhibited significantly lower vestibulo-ocular reflex (VOR) values in the SHA test compared to controls. Greater hearing loss severity was associated with lower VOR gain values. No statistically significant differences were observed between groups in caloric test results or vHIT VOR gain values. However, corrective saccades during vHIT were identified exclusively in patients with hearing loss and occurred in approximately 15% of cases. Furthermore, the age of independent walking was significantly delayed in the study group compared to controls. Conclusions: Congenital bilateral SNHL is associated with vestibular dysfunction, as evidenced by abnormal SHA test results and the presence of corrective saccades in vHIT. These patients may also experience delayed motor development. These findings suggest that vestibular dysfunction may be present in patients with congenital sensorineural hearing loss and may have functional implications. Full article

Alcohol use disorder is associated with substantial neurologic and systemic morbidity, but its relationship with audiovestibular dysfunction has not been clearly synthesized. This systematic review summarized human primary clinical evidence on auditory and vestibular manifestations, diagnostic findings, treatment, and prognosis in alcohol use disorder. PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect were searched from inception to 4 February 2026; the review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261301021). Because study designs, clinical contexts, and outcome measures were highly heterogeneous, a structured qualitative synthesis was performed. Twelve human primary clinical studies were included. The available evidence supported objective auditory dysfunction, most commonly sensorineural hearing impairment with frequent high-frequency involvement. Vestibular involvement was also reported, but the evidence was smaller and less phenotypically specific, consisting mainly of syndromic reports, broad peripheral/central classifications, and historical nystagmographic findings. Direct treatment evidence was very limited; improvement after thiamine replacement was reported in alcohol-related Wernicke-spectrum presentations, but no established disease-specific therapy was identified. Overall, current human clinical evidence supports heightened clinical awareness but not disease-specific screening algorithms or targeted therapeutic recommendations. Better prospective studies using contemporary phenotype-based audiovestibular assessment are needed. Full article

Background: Among the complications caused directly or indirectly by the Human Immunodeficiency Virus (HIV) are alterations in the auditory system. Children who are HIV-exposed but uninfected (HEU) appear to have a higher risk of hearing loss (HL) compared to their unexposed peers, but a lower risk than those infected with HIV. However, the literature remains inconclusive regarding this association. This study aims to evaluate the hearing function of HEU infants during the first months of life and to correlate these findings with maternal, gestational, and neonatal variables. Methods: This prospective cohort study included all HIV-exposed infants born in a quaternary hospital in southern Brazil between 2021 and 2023. Maternal, gestational, and neonatal data were collected, as well as the results of neonatal auditory screening. At approximately 6 months of age, otolaryngological and audiological assessments were performed, including wideband tympanometry and electrophysiological evaluation using Auditory Brainstem Response with frequency-specific stimuli. The prevalence of hearing loss refers to the number of infants affected. Results: Thirty-eight infants, with a mean age of 8 months (±3.3), completed the study. Of these, 1 (2.6%) presented with bilateral sensorineural HL, and 13 (34.2%) presented with conductive HL, with 6 cases being unilateral and 7 bilateral. No associations were found between hearing loss and maternal, gestational, or neonatal variables, except for maternal CD4 count, where higher CD4 cell counts were associated with an increased risk of conductive HL. Conclusion: The findings provide relevant data on auditory alterations in HEU infants, demonstrating a high prevalence of conductive HL. These results highlight the importance of monitoring the hearing of these children during the first years of life. Full article