Salvatore Ronsivalle

Background: Hearing loss is a widespread sensory disorder affecting over 1.5 billion people worldwide, with the number projected to exceed 700 million by 2050. It imposes social and economic burdens across all ages and regions. Approximately half of adult cases are preventable, but the underlying causes are complex, with 75–80% due to autosomal recessive genetic factors and key roles for mutations in genes such as GJB2. Advances in sequencing technologies have accelerated gene discovery, but challenges remain in interpreting variants. Epigenetic mechanisms such as DNA methylation and histone modifications are increasingly recognized as crucial in auditory biology and could offer new biomarkers and therapeutic targets. Integrating epidemiological, genetic, and epigenomic data is essential to developing targeted prevention and treatment strategies to reduce the global burden of hearing loss. Methods: This narrative review examines recent genomic and epigenomic advances in hearing loss, with particular emphasis on molecular mechanisms, emerging diagnostic applications, and translational therapeutic opportunities. A comprehensive review of current epidemiological data, genetic studies, and epigenomic research was conducted using the peer-reviewed literature from international databases. Key areas of interest include inheritance patterns, molecular pathways, and recent advances in omics technologies. Results: Epigenetic mechanisms, including DNA methylation and histone modifications, are increasingly recognized as important regulators of cochlear development and hair cell survival, although much of the current evidence remains preclinical. Studies suggest that peripheral epigenetic signatures may serve as biomarkers for early diagnosis and risk stratification. Conclusions: Integrating established screening pathways with epidemiological trends and molecular knowledge offers a promising path toward precision medicine in hearing care. Connecting these domains is essential to developing equitable and effective interventions and addressing persistent global disparities in hearing health. This review highlights the evolving landscape of auditory genetics and epigenetics and outlines future directions for translational research and personalized therapy.

Background: Hearing loss is one of the most common yet often overlooked sensory deficits worldwide, with consequences extending well beyond auditory function. Mounting evidence highlights the complex interrelationships among hearing loss, cognitive decline, and psychosocial well-being. Neural mechanisms underlying this association include increased cognitive load, cortical reorganisation, and social isolation, which mediate the impact of auditory deprivation on the brain and mental health. Furthermore, hearing impairment is consistently associated with a higher risk of depression and anxiety, particularly when the duration of untreated deafness is prolonged. Methods: This narrative review summarises recent longitudinal and neuroimaging studies investigating the effects of hearing loss and the timing of intervention with hearing aids. The review focuses on evidence addressing cognitive, psychological, and neural outcomes in relation to early versus delayed amplification. Results: Across multiple studies, early adoption of hearing aids within a limited timeframe after diagnosis is linked to better cognitive performance, lower depressive symptom scores, and more preserved neural network integrity. Experimental evidence supports the existence of sensitive periods for auditory intervention, during which brain plasticity allows for optimal reorganisation and recovery of function. Conversely, delayed amplification may lead to irreversible cortical changes and persistent psychosocial distress. Despite this, several barriers—healthcare accessibility, patient attitudes, and economic constraints—continue to delay timely intervention. Conclusions: Early identification and management of hearing loss are critical to preserve cognitive and emotional health. An integrated approach addressing both hearing and cognitive well-being, supported by patient education and personalised care strategies, may maximise the benefits of amplification and improve overall quality of life.