Lucy S. French, Carla B. Mellough, Fred K. Chen, and Livia S. Carvalho | Frontiers Cell. Neuroscience | 09 July 2020 | Sec. Cellular Neuropathology | Volume 14 | 2020 | doi.org/10.3389/fncel.2020.00183
Abstract
Usher syndrome is a genetic disorder causing neurosensory hearing loss and blindness from retinitis pigmentosa (RP). Adaptive techniques such as braille, digital and optical magnifiers, mobility training, cochlear implants, or other assistive listening devices are indispensable for reducing disability. However, there is currently no treatment to reduce or arrest sensory cell degeneration. There are several classes of treatments for Usher syndrome being investigated. The present article reviews the progress this research has made towards delivering commercial options for patients with Usher syndrome.
Introduction
Usher syndrome is a group of autosomal recessive disorders characterized by congenital neurosensory hearing loss, progressive night vision impairment, and constriction of the visual field due to retinitis pigmentosa (RP). Some forms of Usher syndrome may also have varying levels of vestibular dysfunction resulting in loss of balance. It is the most common form of inherited deaf-blindness (El-Amraoui and Petit, 2014) affecting an estimated 1 in 6,000 people worldwide (Kimberling et al., 2010). Usher subtypes (1, 2, and 3; Table 1) are graded according to the severity of symptoms and age of onset. Type 1 patients are born profoundly deaf and experience pre-pubertal onset of progressive vision loss caused by RP. The majority of type 1 patients also have developmental motor delays caused by vestibular dysfunction. Type 2 patients have mild to moderate congenital hearing loss with RP diagnosed during puberty. Hearing loss in type 3 patients is progressive and post-lingual, while RP onset may be delayed until mid-adulthood (Reiners et al., 2006). The clinical presentation of RP begins with night blindness caused by the degeneration of rod photoreceptor cells. Subsequent constriction of the visual field results in a “tunnel vision” effect caused by the centripetal progression of cone photoreceptor cell loss. In classical RP, the death of cones may be secondary to rod degeneration and this may ultimately lead to complete loss of vision in advanced age (Hartong et al., 2006). Many other inherited retinal diseases are associated with deafness (Table 2) such as cone-rod dystrophy and hearing loss-1 (CRDHL1, OMIM #617236), diabetes and deafness, maternally inherited (MIDD, OMIM #520000) and Leber congenital amaurosis (LCA) with early-onset deafness (LCAEOD, OMIM #617879). This review is limited to the combination of RP and deafness, the classical presentation of Usher syndrome.