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Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular impairment. With a prevalence of 4–17/100,000, it is the most common cause of deaf-blindness worldwide. Genetic research has provided crucial insights into the complexity of US. Among nine confirmed causative genes, MYO7A and USH2A are major players in US types 1 and 2, respectively, whereas CRLN1 is the sole confirmed gene associated with type 3. Variants in these genes also contribute to isolated forms of hearing loss and RP, indicating intersecting molecular pathways. While hearing loss can be adequately managed with hearing aids or cochlear implants (CIs), approved RP treatment modalities are lacking. Gene replacement and editing, antisense oligonucleotides, and small-molecule drugs hold promise for halting RP progression and restoring vision, enhancing patients’ quality of life. Massively parallel sequencing has identified gene variants (e.g., in PCDH15) that influence CI results. Accordingly, preoperative genetic examination appears valuable for predicting CI success. To explore genetic mutations in CI recipients and establish correlations between implant outcomes and involved genes, we comprehensively reviewed the literature to gather data covering a broad spectrum of CI outcomes across all known US-causative genes. Implant outcomes were categorized as excellent or very good, good, poor or fair, and very poor. Our review of 95 cochlear-implant patients with US, along with their CI outcomes, revealed the importance of presurgical genetic testing to elucidate potential challenges and provide tailored counseling to improve auditory outcomes. The multifaceted nature of US demands a comprehensive understanding and innovative interventions. Genetic insights drive therapeutic advancements, offering potential remedies for the retinal component of US. The synergy between genetics and therape

Background: Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. Methods: The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Results: Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). Conclusions: Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if centra

Mutations in mitochondrial DNA (mtDNA) have been shown to be an important cause of sensorineural hearing loss (SNHL). In this study, we performed a clinical and genetic analysis of 169 hearing-impaired patients and some of their relatives suffering from idiopathic SNHL, both familial and sporadic. The analysis of four fragments of their mtDNA identified several polymorphisms, the well known pathogenic mutation, A1555G, and some novel mutations in different genes, implying changes in the aminoacidic sequence. A novel sporadic mutation in 12S rRNA (MT-RNR1), not previously reported in the literature, was found in a case of possible aminoglycoside-induced progressive deafness., Funding agency:Ospedale Infantile e Pie Fondazioni Burlo Garofolo e dott. Alessandro ed Aglaia de Manussi' Trieste