Introduction and clinical aspects in Usher syndromes

Abstract Usher syndrome (USH, OMIM 276900, OMIM 276905, OMIM 605472, ORPHA: 886) is the most prevalent deaf‐blindness of genetic origin. It is a recessive inherited disease characterized by sensorineural hearing loss (HL), visual loss due to retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. Prevalence estimates range from 3.2 to 6.2/100,000. Patients with USH are classified into three clinical subtypes (USH1, USH2, or USH3), based on the severity and progression of hearing impairment and the presence or absence of vestibular dysfunction. Usher syndrome type I (USH1) is the most severe type, characterized by severe to profound congenital sensorineural hearing loss, vestibular dysfunction and prepubertal onset of RP eventually leading to legal blindness. USH2 is characterized by moderate to severe hearing impairment, normal vestibular function and later onset of retinal degeneration. USH3 displays progressive hearing loss, RP and variable vestibular phenotype. In the last years, next generation sequencing (NGS) techniques have revolutionized the world of the molecular genetic diagnosis. NGS has allowed to molecularly characterize a high number of patients, thus permitting to establish some phenotype‐genotype correlations that had been elusive to date.