USH1C Vision and Balance Natural History Studies and Approach to Sharing Clinical Data

Abstract

Purpose : Usher syndrome (USH) is a rare genetic disorder characterized by the multi-sensory loss of hearing, balance, and vision. Four clinical types (USH1-4) and 10 genes (subtypes) are associated with USH based on the severity of the hearing loss, presence of imbalance, and age of onset of the vision loss. Approximately 10% of USH1 is caused by mutations in the USH1C gene, but nearly all cases among the Acadian populations in Canada and Louisiana are caused by the c.216G>A mutation in the USH1C gene (USH1C). The loss of hearing, balance, and vision are present at different ages in USH patients, however, the natural clinical course – when these losses begin and how quickly they progress – is not known.

Methods : We are conducting several natural history studies (NHSs) with USH1C patients at all stages of disease progression to improve our understanding of the natural progression, and identify potential clinical trial participants and robust outcome measures that can be used to guide future clinical trials.

Results : Currently, 109 participants are enrolled in a retrospective NHS of USH in Louisiana and throughout the world. Of these, 75 have genetic confirmation of USH1C disease and are currently being invited to participate in two prospective NHSs on vestibular and visual loss in USH1C. Demographic, eye and ear histories, genetic, patient-reported surveys, and longitudinal hearing, balance, and vision clinical data are being collected from pediatric, young-adult, and adult USH1C patients (n=12/50). Additionally, we have developed several databases designed to store, analyze, and share longitudinal USH1C genotype-phenotype data.

Conclusions : Natural history and outcome measures data for USH1C patients are important to guide treatment trials. The approach to develop these studies in USH1 patients highlights challenges specific to this population.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.