Clinical and molecular genetics of Usher syndrome

Abstract

Usher syndrome is an autosomal-recessive disorder manifested by hearing impairment, retinitis pigmentosa (RP), and variable vestibular deficit. Recent progress in the characterization of the genetics of Usher syndrome has shown that this disorder is phenotypically and genetically complex. This progress impacts the approach of the clinicians in the study of patients who may potentially have Usher syndrome. There are three major phenotypic classes: Usher I, II, and III. Usher I is distinguished from Usher II by having a more severe audiologic involvement and by the presence of vestibular areflexia. Usher III has a progressive hearing loss with variable vestibular involvement. A minimum of three genes have been identified as being responsible for Usher I; two have been identified as being responsible for Usher II. It is not yet clear whether other manifestations such as progressive hearing loss, associated mental retardation, or other physical anomalies are associated with the known Usher genes or whether they represent as yet undiscovered genetic disorders. As progress towards the identification of the Usher genes is made, the clinician will gradually gain new and effective diagnostic procedures for the identification and delineation of the Usher syndromes.