Usher Syndrome - Clinical and Molecular Studies

The Usher Syndromes (USH), characterized by autosomal recessive inheritance, are genotypically distinct diseases which share specific phenotypic characteristics. Affected individuals have congenital neurosensory hearing impairment of variable severity and a progressive pigmentary retinal degeneration commonly referred to as retinitis pigmentosa. Interfamilial differences in USH patients are greater than intrafamilial differences and investigators have proposed at least two distinct phenotype types; Usher Syndrome type 1 (USH 1) and Usher Syndrome type 2 (USH 2) (Fishman 1983). Patients with USH 1 are profoundly deaf from birth, have unintelligible speech and absent vestibular function. Nightblindness is apparent in the 1st or 2nd decade accompanied by an extinguished electroretinogram (ERG) and profound loss of visual field. Patients with USH 2 can have moderate to severe hearing loss and normal vestibular function. Nightblindness occurs in the 2nd or 3rd decade, there is variable field loss and variable response by the ERG (Fishman 1983). Heterogeneity has been verified by linkage studies and at least three USH 1 loci and two USH 2 loci are known (Kimberling et al 1990; Lewis et al 1990; Kaplan et al 1992; Smith et al 1992a.) With increasingly sophisticated clinical testing, subtle differences may permit a more accurate distinction between the two USH phenotypes. The purpose of this study is to classify as accurately as possible these patients' clinical features by careful audiologic, vestibular, psychophysical and electrodiagnostic testing and correlate these with the genetic mutations identified through linkage studies and eventually to the genes (genetic mutations) as they become identified.