Search Results (520)

Introduction: Noggin encoding (NOG) gene plays a critical role in early embryogenesis and development of bones, joints, cartilage, eyes, and neural tissue. The NOG gene encodes the noggin protein. Noggin is the only secreted inhibitor of bone morphogenetic protein (BMP) that is associated with abnormal phenotypes in humans. The most commonly observed manifestations of NOG gene mutations include bilateral conductive hearing loss, proximal symphalangism, broad thumbs, hyperopia, and a distinct facial appearance. This genetic disorder was first reported in 1990 by Teunissen and Cremers. Since then, various phenotypic presentations of NOG mutation have been reported, leading to the introduction of the term NOG-related symphalangism spectrum disorder (NOG-SSD). Case report: In this report, we describe a family (mother and daughter) with bilateral mixed hearing loss. Both patients had hyperopia, distinct facial appearance with hemicylindrical nose, broad thumbs, and syndactyly of the second and third toes. Genetic testing confirmed a NOG gene mutation. Bilateral stapedotomy was successfully performed, resulting in significant hearing improvement. However, due to sensorineural component of hearing loss, complete hearing recovery was only achieved with the use of hearing aids. Discussion: The etiology of the sensorineural component of hearing loss in NOG-SSD remains unclear. In animal models, the NOG gene is essential for inner ear development, while in humans, only middle ear malformations have been reported. The phenotypic variability observed in individuals with NOG mutations is very wide, suggesting that the sensorineural component of hearing loss could represent one of the possible manifestations. Conclusions: Conductive hearing loss is the primary manifestation of the NOG-SSD, and all previously reported cases of NOG gene mutations have presented exclusively with conductive hearing loss. It is possible that additional genetic factors, not necessarily directly related to the NOG gene but present in this family, contribute to the development of the sensorineural component of hearing loss, although thorough genetic testing did not reveal any additional mutation. This is, to our knowledge, the first report of mixed hearing loss associated with a NOG mutation confirmed preoperatively. Further studies are needed to determine whether the sensorineural component represents a primary manifestation or arises from secondary mechanisms. Full article

Background and Objectives: Sensorineural hearing loss (SNHL) is influenced by various causes, including thyroid diseases. For example, hypothyroidism and thyroid autoimmunity can damage the inner ear through hormonal, immune, and vascular mechanisms. Vestibular disorders like Ménière’s disease (MD) and benign paroxysmal positional vertigo (BPPV) also show possible associations with thyroid dysfunction. Materials and Methods: A review following PRISMA guidelines searched PubMed, Scopus, and Google Scholar for studies linking thyroid disorders with inner ear dysfunction. Results: Out of 985 screened records, 30 studies met inclusion criteria, involving various thyroid disorders, primarily hypothyroidism and autoimmune thyroiditis. Scientific evidence supports a correlation between hypothyroidism and hearing impairment. However, some studies also suggest a link between hyperthyroidism and inner ear disorders, particularly focusing on the role of autoimmunity in this context. Concerning vestibular dysfunction, the available studies are less abundant and support a significant association between thyroid disease and Meniere’s disease. Conclusions: There is a clear correlation between hypothyroidism and auditory function. A substantial body of literature also supports an association with vestibular disorders, although some discrepancies remain. Further research is needed to elucidate the underlying pathophysiological mechanisms (e.g., autoimmune, vascular, metabolic) involved with this correlation. Full article

Congenital human cytomegalovirus (HCMV) infection is the most common vertically transmitted viral infection, and it affects 1 in 200 live births worldwide. While neonates are often asymptomatic at birth, congenital HCMV infection can result in long-term complications, including microcephaly, sensorineural hearing loss, and neurodevelopmental abnormalities. Developing antiviral strategies for the treatment and prevention of congenital HCMV infections is a global public health priority. However, licensed anti-HCMV vaccines are not yet available, and therapeutic options for use during pregnancy remain limited. The complement system is a crucial component of the innate immune system that plays essential roles in both fetal development and maternal defense against infectious pathogens. In cases of congenital HCMV infection, complement may contribute to the successful containment of the virus, but dysregulation and overactivation could concurrently drive tissue-damaging inflammation. This review discusses the known roles of the complement system in fetal development and in HCMV pathogenesis and synthesizes existing research to develop the hypothesis that a dysregulated complement system is a key mechanism in the development of congenital HCMV-related pathogenesis and neurodevelopmental sequelae. We explore how HCMV may perturb the complement system during pregnancy and use one inhibitor example to illustrate the broader potential of targeting complement in limiting disease. Full article

Background/Objectives: Chiari malformation (CM) type I is an uncommon condition that can be associated with a variety of neurological and otoneurological symptoms, including sensorineural hearing loss. The aim of this paper is to analyze the association between type I CM and hearing loss. Methods: A review of the literature was performed using PubMed/MEDLINE, EMBASE, and Cochrane Library databases, according to PRISMA criteria for scoping review (from 2000 to April 2025). Results: A total of 8 articles and 139 patients with type I CM have been included; the majority of studies focused on women, with a mean age of 38.5 years (range: 10–44 years). In two cases, surgery was necessary for restoring normal hearing thresholds. Conclusions: To date, the pathophysiological mechanisms related to type I CM and hearing loss are not fully understood yet; further studies are necessary to clarify these features and to evaluate the correct management of these patients. Full article

Background/Objectives: The primary objective of the present study was to investigate early global development in children after one year of cochlear implant (CI) use. The secondary objective was to investigate the role of variables such as age at CI activation, gender, and parental schooling in early global development in children with a CI. Methods: The study sample included 24 subjects. All children were affected by severe-to-profound congenital bilateral sensorineural hearing loss (HL). The HL was diagnosed between 1 and 23 months of age (median 3 months) and participants underwent cochlear implant activation at 9–25 months (median 14 months). Participants were evaluated before CI surgery and after one year of CI use using the Italian version of the Griffiths III scales. Results: The general developmental quotient remained stable, as did the developmental quotients on scales A, C, D, and E. However, the development quotients on scale B, corresponding to the domain of “language and communication,” underwent a significant increase (p value < 0.05). There was a statistically significant negative effect of “age at CI activation” on both DQ at scale B (t − 3.457) and GDQ (t − 42.069). Maternal schooling had a significant positive effect on GDQ and DQ for scales A to D (p. value < 0.05). Conclusions: After one year of CI use, a significant improvement in the early global development of children was found in the language and communication domain. The age at CI activation and the level of the mother’s education were found to be related to early global development. Full article

Congenital cytomegalovirus (CMV) is a major cause of neonatal morbidity, particularly sensorineural hearing loss, yet its early detection remains challenging. While urinary PCR is the current diagnostic gold standard, its implementation in neonatal settings is often limited by feasibility issues. Salivary PCR presents a more practical alternative, but its diagnostic accuracy has remained uncertain. This systematic review and meta-analysis aimed to evaluate the performance of salivary PCR compared to urinary PCR in detecting congenital CMV in neonates. Following PRISMA guidelines, 15 observational studies involving 29,617 neonates were analyzed using a random-effects model. Pooled sensitivity and specificity were 0.99 and 1.00, respectively, with a negative predictive value (NPV) of 1.00 and a positive predictive value (PPV) of 0.91, despite moderate heterogeneity. Subgroup analysis showed high diagnostic performance across general neonates, infants of seropositive mothers and high-risk neonates (referring to neonates that are small for their gestational age (SGA), neonates who failed hearing screening, and neonates with CMV-related congenital abnormalities). The general group had the highest specificity (0.999), while high-risk neonates showed the highest sensitivity (0.981). Across all groups, NPV remained consistently above 0.994, with PPV ranging from 0.848 to 0.981. These findings confirm that salivary PCR is a highly accurate and feasible tool for congenital CMV diagnosis. Full article

Objective: Children with cleft lip and/or palate (CLP) commonly present with otitis media with effusion (OME), with increased referrals for newborn hearing screening (NHS). Auditory brainstem response (ABR) testing with OME may mimic sensorineural hearing loss. This study evaluated NHS and ABR findings on and optimal timing for ABR reassessment after tympanostomy in patients with CLP. Methods: We conducted a retrospective study reviewing 271 CLP cases at our institution. The data included the cleft type, NHS results, ABR findings, OME incidence, and tympanostomy rate. Subgroup analyses compared ABR results before and after tympanostomy and via postoperative timing. Statistical comparisons were performed using the Mann–Whitney U test and Fisher’s exact test. Results: The NHS referral rate was 14.0%, and the OME incidence was 48.7%. These cases occurred in patients with cleft palate involvement, with an OME prevalence of 73.4%. Tympanostomy was performed in 72.6% of cases. Among 36 ears tested pre- and post-tympanostomy, wave V thresholds improved from 61.67 ± 16.08 to 34.72 ± 6.54 dBnHL (p < 0.0001), and wave I latency decreased from 2.27 ± 0.36 to 1.76 ± 0.12 ms (p < 0.0001). Postoperative wave V thresholds were significantly better in the ≥15-day group (p = 0.037), with 65% (17/26) of ears showing thresholds <40 dBnHL compared to 25% (3/12) in the <15-day group (p = 0.035). No timing-related differences were found regarding wave I latency. Conclusions: Tympanostomy significantly improved the ABR results in children with CLP and OME. Reassessment on or after postoperative day 15 may yield more accurate results and may help to reduce parental anxiety. Full article

Childhood cancer treatments, including chemotherapy, radiation therapy, and combined modalities, pose significant risks to auditory function due to their ototoxic effects. Cisplatin, a chemotherapeutic agent commonly used in pediatric oncology, causes dose-dependent irreversible sensorineural hearing loss by damaging the inner ear structures, primarily through the generation of reactive oxygen species and the activation of apoptotic pathways. Radiation therapy exacerbates these effects, contributing to both sensorineural and conductive hearing loss via mechanisms such as vascular injury, inflammation, and fibrosis. The severity of hearing loss is influenced by the treatment timing, the cumulative dose, patient age, genetics, and concurrent therapies. The damaging effects of chemotherapy and radiation extend beyond the cochlea, involving the surrounding temporal bone as well as multiple levels of the auditory pathway. While pediatric patients may be candidates for bone-anchored hearing devices or cochlear implants, the need for serial imaging and the potential for implant-related MRI artifacts can complicate the timing of hearing rehabilitation. Moreover, the impact on the subcortical and cortical auditory structures may further influence the rehabilitation outcomes. This scoping review lays the foundation for future clinical and research efforts focused on the development of comprehensive pediatric guidelines for hearing preservation, monitoring, and rehabilitation, while also fostering multidisciplinary collaboration. Full article

Cisplatin is an alkylating chemotherapeutic drug used in the treatment of many pediatric solid tumors, and cisplatin ototoxicity is characterized by sensorineural, bilateral, irreversible, and progressive hearing loss. The aim of this study is to identify biomarkers that may serve as predictors of cisplatin-induced ototoxicity in pediatric cancers. In our preliminary study, patients with severe hearing loss were analyzed using the comparative genomic hybridization (CGH) method. Mutations were identified in the following genes: ADAM6, SIX3, GNAS, NDUFV1, H19, DEFA4, and ZIM2. Based on these data, we aimed to investigate the mutation status of these candidate genes in a larger population of pediatric cancer patients treated with cisplatin. DNA samples were extracted from the mononuclear cells of peripheral blood samples obtained from 82 patients. These genes were analyzed using the RT-PCR technique, and ototoxicity was assessed using the Brock and Muenster classifications. Hearing loss was detected in 28% of patients; 76.8% and 23.2% had mild and severe hearing loss, respectively. A significant correlation was found between ZIM2 gene amplification and the presence of ototoxicity (rho = 0.461, p = 0.003), especially in advanced-stage cancer patients with severe hearing loss (rho = 0.38, p = 0.017). Our findings suggest that ZIM2 is a promising biomarker for predicting cisplatin ototoxicity. Full article

Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection, affecting approximately 0.5–2% of newborns, and is the leading non-genetic cause of sensorineural hearing loss and neurological impairment. The most severe outcome occurs following primary maternal infection during the first trimester of pregnancy, and up to 40–50% of affected fetuses sustain permanent damage. Diagnosis relies on early prenatal screening through maternal serum testing, optimally performed in the first trimester, followed by confirmatory amniocentesis after 17 weeks’ gestation. Prenatal imaging with ultrasound and magnetic resonance imaging (MRI) plays a critical role in the identification of fetal brain abnormalities. Prevention strategies emphasize hygiene measures aimed at reducing maternal exposure to bodily fluids of young children, particularly prior to conception and during early pregnancy. Despite progress in vaccine development, currently available ones demonstrate modest efficacy. This review presents a comprehensive summary of congenital CMV infection, addressing its epidemiology, pathogenesis, diagnostic approaches, clinical presentation, and preventive measures, with a focus on recent advances in vaccine research. Full article

Background/Objectives: This research focuses on the increasing presence of older workers in the labor market, a group particularly vulnerable to hearing problems due to age-related changes and prolonged noise exposure. Methods: The research combines theoretical and empirical approaches to investigate the impact of noise on the workplaces of older employees. The empirical component is based on two primary methods: a survey and audiometric testing to assess participants’ hearing abilities. The study included a sample of 50 older workers, all with diagnosed hearing loss. Results: The results of the survey showed that most older workers are regularly exposed to noise at work, which has long-term negative effects on their hearing. This highlights the need to introduce appropriate protective measures such as personal protective equipment, insulation of noise sources, and raising awareness about the dangers of noise. In addition to the questionnaire survey, the analysis of hearing measurements revealed that all respondents had significant bilateral hearing loss, with sensorineural hearing loss being the most prevalent type. Conclusions: This study highlights the negative impact of chronic noise exposure in the workplace on the hearing, communication and productivity of older workers and emphasizes the importance of combining preventive measures, hearing protection and workplace adaptations to promote their well-being and performance. Full article

Background and Objectives: Cochlear implantation (CI) is a surgical procedure that offers significant benefits to individuals with sensorineural hearing loss, particularly in pediatric patients, as it can prevent long-term cognitive impairment. Despite the devices being designed for lifelong use, complications may necessitate explantation and subsequent reimplantation. Materials and Methods: Our retrospective study analyzes the incidence and causes of such procedures in pediatric CI patients over a period of 15 years, from May 2009 to June 2025. The study included patients aged between 8 months and 17 years, recording their age, the manufacturers of their first and second implants, the reasons for explantation and reimplantation, and the type of electrode array used during the second surgery. Results: During the study period, a total of 440 cochlear implantations were performed in our department. The primary causes of explantation in our study group were device hardware failures in 2.27% of cases, seromas over the implant body or antenna in 0.68% of cases, spontaneous extrusion in 0.22% of cases, and local trauma with electrode displacement in 0.22% of cases. The study confirmed that hardware failures were the most common reason for reimplantation, with an incidence influenced by the device manufacturer and the extent of trauma to the device. Surgical observations highlight the challenges regarding electrode reimplantation and available electrode choices for the surgeon. Conclusions: The use of superior materials and advanced research in manufacturing can enhance implant reliability and reduce the number of surgical procedures required in the long term for pediatric patients. Any type of electrode array can be utilized in reimplantations if meticulous surgical techniques are applied. Full article

Hearing loss is often caused by genetic and environmental factors, with inherited mutations responsible for 50–60% of cases. The GJB2 gene, encoding connexin 26, is a major contributor to nonsyndromic sensorineural hearing loss (NSHL) due to its role in cellular communication critical for auditory function. In Taiwan, common deafness-associated genes include GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. The most common pathogenic genes is GJB2 mutations and the hearing level in children with GJB2 p.V37I/p.V37I or p.V37I/c.235delC was estimated to deteriorate at approximately 1 decibel hearing level (dB HL)/year. We found another common mutation in Taiwan Biobank, GJB2 p.I203T, which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest GJB2 whole genetic screening is recommended for clinical management and prevention strategies in Taiwan. This study used data from the Taiwan Biobank to analyze allele frequencies of GJB2 gene variants. Predictive software (PolyPhen-2 version 2.2, SIFT for missense variants 6.2.1, MutationTaster Ensembl 112 and Alphamissense CC BY-NC-SA 4.0) assessed the pathogenicity of specific mutations. Additionally, 82 unrelated NSHL patients were screened for mutations in these genes using PCR and DNA sequencing. The study explored the correlation between genetic mutations and the severity of hearing loss in patients. Several common GJB2 mutation sites were identified from the Taiwan Biobank, including GJB2 p.V37I (7.7%), GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%). Bioinformatics analysis classified GJB2 p.I203T as pathogenic, while GJB2 p.V27I and GJB2 p.E114G were considered polymorphisms. Patients with GJB2 p.I203T mutation experienced more severe hearing loss, emphasizing the potential interaction between the gene in auditory impairment. The mutation patterns of GJB2 in the Taiwanese population are similar to other East Asian regions. Although GJB2 mutations represent the predominant genetic cause of hereditary hearing loss, the corresponding mutant proteins exhibit detectable aggregation, particularly at cell–cell junctions, suggesting at least partial trafficking to the plasma membrane. Genetic screening for these mutations—especially GJB2 p.I203T (6%), GJB2 p.V27I (31%), and GJB2 p.E114G (22%)—is essential for the effective diagnosis and management of non-syndromic hearing loss (NSHL) in Taiwan. We found GJB2 p.I203T which were identified in our data and individuals carrying this mutation experienced more severe hearing loss, suggesting a synergistic effect of these mutations on auditory impairment. We suggest whole GJB2 gene sequencing in genetic screening is recommended for clinical management and prevention strategies in Taiwan. These findings have significant clinical and public health implications for the development of preventive and therapeutic strategies. Full article

Background/Objectives: Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss (SNHL) and pigmentation anomalies. While hearing impairment is a well-established feature of WS, vestibular dysfunction is also reported. This study aimed to investigate vestibular deficits in pediatric WS patients with SNHL, correlating these findings with molecular, audiometric, and radiological data to establish distinct phenotypic profiles for each WS subtype and associated pathogenic variants. Methods: This retrospective study included children with a genetically confirmed diagnosis of WS who underwent vestibular, auditory, and inner ear radiological assessments as part of their routine medical care between July 2000 and May 2022. Data were collected from medical records, including medical history, clinical findings, and assessment results. Results: Vestibular dysfunction was found to be highly prevalent, affecting 64% of the cohort, often impacting the canal sensory organ (89%) and occasionally the otolithic function (33%). Patients with SOX10 pathogenic variations exhibited a markedly higher risk of vestibular dysfunction, highlighting the unique role of SOX10 in inner ear development. Notably, inner ear malformations were identified in all SOX10-mutated subjects, whereas such anomalies were rare among individuals with other WS gene variants, occurring in only two additional cases with minor malformations. Conclusions: This study reveals a significant prevalence of vestibular deficits in pediatric WS patients with SNHL, emphasizing the need for routine vestibular assessments. The higher prevalence and severity of vestibular impairments in SOX10-mutated patients underscore the importance of molecular analysis in clinical diagnosis and management. Full article

Background/Objectives: Sudden sensorineural hearing loss (SSNHL) represents a challenging clinical entity with variable prognosis. Audiometric curve configuration has been proposed as a predictor of recovery. This study aimed to evaluate the association between audiogram morphology at onset and hearing outcome in patients with idiopathic unilateral SSNHL treated with standardized therapy. Methods: We retrospectively analyzed 156 patients with idiopathic SSNHL. Hearing thresholds at key frequencies were measured at baseline and 4 weeks post-treatment. Patients were categorized into upsloping, flat, downsloping, or U-shaped audiogram subgroups. Recovery was classified into four levels. Comparisons were made across subgroups for audiometric and laboratory data using ANOVA and chi-square tests. Results: Baseline PTA values were comparable across audiogram subgroups (p = 0.12). Hearing recovery differed significantly according to audiogram configuration (chi-square, p < 0.001), with upsloping and U-shaped patterns showing the best outcomes. Flat and downsloping curves were associated with poorer recovery, lower HDL, and elevated NLR values. Conclusions: Audiogram configuration is a relevant prognostic marker in SSNHL. Patterns linked to adverse metabolic and inflammatory profiles may benefit from tailored treatment strategies in a personalized medicine framework. Full article