Congenital sensorineural hearing loss (SNHL) is one of the most common permanent sensory disorders identified during infancy, with an estimated global incidence of 1–3 per 1,000 live births (1). Approximately 50–60% of congenital hearing loss has a genetic basis and is broadly classified into no syndromic and syndromic forms. Among the syndromic disorders, Usher syndrome is the most common inherited cause of combined deaf-blindness and accounts for approximately half of all hereditary deaf-blindness cases worldwide (2). Despite advances in neonatal hearing screening, early recognition of Usher syndrome remains challenging because visual manifestations usually develop years after congenital hearing impairment is detected. Usher syndrome is an autosomal recessive disorder characterized by varying combinations of sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular dysfunction. Clinically, it is classified into three major subtypes according to the severity and timing of these manifestations. Usher syndrome type 1 (USH1) presents with profound congenital hearing loss, vestibular areflexia, and early-onset RP; USH2 is characterized by congenital moderate-to-severe hearing loss with preserved vestibular function and adolescent-onset RP; whereas USH3 demonstrates progressive post-lingual hearing loss accompanied by variable vestibular and retinal involvement (3,4). A major diagnostic challenge in Usher syndrome is the asynchronous progression of auditory and visual manifestations. Hearing impairment is typically identified during infancy through newborn hearing screening programs, whereas retinal degeneration remains clinically silent until later childhood or adolescence, when patients develop night blindness, peripheral visual field loss, and progressive visual impairment (2). Consequently, many affected children undergo prolonged audiological rehabilitation without recognition of the underlying syndromic diagnosis, delaying genetic counselling, ophthalmological surveillance, and timely multidisciplinary intervention. Universal Newborn Hearing Screening (UNHS), based on automated auditory brainstem response (AABR) and transient evoked otoacoustic emissions (TEOAE), has substantially improved the early identification of congenital hearing loss and is now implemented in many healthcare systems worldwide (1). However, these screening programs are designed to detect hearing impairment rather than determine its underlying etiology. As a result, they cannot reliably distinguish isolated nonsyndromic deafness from progressive hereditary syndromes such as Usher syndrome. This limitation contributes to delayed molecular diagnosis, particularly in settings where access to genetic testing and specialized ophthalmic assessment remains limited. Recent advances in molecular diagnostics have transformed the clinical management of inherited retinal disorders. Next-generation sequencing (NGS) enables comprehensive genetic evaluation of children with unexplained congenital hearing loss, facilitating earlier identification of pathogenic variants associated with Usher syndrome. In parallel, emerging therapeutic strategies—including gene replacement therapy, antisense oligonucleotides, gene-editing technologies, and retinal neuroprotective approaches—have increased the importance of establishing a definitive diagnosis before irreversible photoreceptor degeneration occurs (3). Early molecular diagnosis therefore provides opportunities for personalized clinical management, genetic counselling, timely ophthalmological monitoring, and potential enrollment in gene-based therapeutic trials. Methods Protocol and Reporting Guidelines This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement to ensure transparent and standardized reporting. The review followed a predefined protocol specifying the research question, eligibility criteria, literature search strategy, study selection process, data extraction, quality assessment, and data synthesis methods. Research Question The review addressed the following question: Among individuals with genetically linked oculo-auditory syndromes, particularly Usher syndrome, how effective are newborn hearing screening, community-based screening, and molecular genetic testing in facilitating early diagnosis compared with conventional symptom-based diagnostic pathways? PICOS Framework Component Description Population (P) Children and adults with genetically linked oculo-auditory syndromes, particularly Usher syndrome (Types I–III), or congenital sensorineural hearing loss at risk for syndromic disease. Intervention (I) Universal newborn hearing screening (UNHS), automated auditory brainstem response (AABR), transient evoked otoacoustic emissions (TEOAE),