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Usher syndrome (USH) is the most common cause of deaf–blindness in humans. It is a clinically and genetically heterogeneous disorder, for which 10 causative genes have been identified so far. The USH genes encode a number of structurally and functionally distinct proteins that form complexes in the inner ear and retina essential for hearing and vision. Animal studies have indicated that the hearing loss associated with USH mainly results from abnormal development of the hair bundle, the mechanoreceptive organelle of the sensory hair cells. In contrast, the molecular and cellular mechanisms underlying the USH visual impairment remain unclear. Although a cure for USH is not yet available, a host of promising therapeutic studies have made progress toward developing an effective treatment for the retinal defects associated with USH. This review provides an outline of the genes and proteins underlying USH, their interactions and functions in the inner ear and retina, and the therapeutic strategies that are und...

Jervell and Lange-Nielsen syndrome is a rare autosomal recessive condition characterized by bilateral profound sensorineural hearing loss, and prolonged QT interval that may result in ventricular tachycardia leading to syncope, cardiac arrest or sudden death. Treatment of the arrhythmias is often life-saving as this condition has a high mortality if untreated. We describe 3 cases of Jervell and Lange-Nielsen syndrome, who presented with profound sensorineural hearing loss and delayed gross motor milestones and have evidence of bilateral vestibular hypofunction on vestibular testing. We suggest that vestibular hypofunction is associated with this syndrome and evaluation of vestibular function may increase the diagnostic yield in the asymptomatic stage of this rare, but severe form of long QT syndrome. Clinicians should consider Jervell Lange-Nielsen in the differential diagnosis of ‘non-syndromic’ profound sensorineural hearing loss presenting with vestibular failure, along with Usher syndrome type...

Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families.