Clinical and Genetic Heterogeneity of Usher Syndrome

Abstract

Usher Syndrome, an autosomal recessive disorder characterized by congenital deafness and retinitis pigmentosa (RP), can be classified into three distinct clinical syndromes called types I, II and III. At least seven genes are responsible for Usher type I, three genes have been localized in Usher II families, and one gene has been identified for Usher type III. Three subtypes of Usher syndrome have been characterized fully enough to permit an assessment of their phenotypic heterogeneity. Usher Ib presents with a surprisingly consistent clinical picture of profound hearing loss, severe vestibular disturbance and early onset RP. Usher type IIa also presents with a fairly specific phenotype, although the occasional progressive hearing loss can make it difficult to distinguish from Usher type III. Usher type Id, in contrast, shows considerable phenotypic range: CDH23 mutations are found in patients with congenital progressive non-syndromic recessive deafness, an Usher type II and III phenotype, atypical mild Usher type I, and typical severe Usher type I that is clinically indistinguishable from that due to mutations in MYO7A.