Natural History and Retinal Structure in Patients with Usher Syndrome Type 1 Owing to MYO7A Mutation

Purpose To evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A -related disease. Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1, characterized by profound congenital deafness, vestibular arreflexia, and progressive retinal degeneration. Design Retrospective case series. Participants Twenty-eight patients from 26 families (age range, 3–65 years; median, 32) with 2 likely disease-causing variants in MYO7A . Methods Clinical investigations included fundus photography, optical coherence tomography, fundus autofluorescence (FAF) imaging, and audiologic and vestibular assessments. Longitudinal visual acuity and FAF data (over a 3-year period) were available for 20 and 10 study subjects, respectively. Main Outcome Measures Clinical, structural, and functional characteristics. Results All patients with MYO7A mutations presented with features consistent with Usher type 1. The median visual acuity for the cohort was 0.39 logarithm of the minimum angle of resolution (logMAR; range, 0.0–2.7) and visual acuity in logMAR correlated with age (Spearman's rank correlation coefficient, r  = 0.71; P  0.0001). Survival analysis revealed that acuity ≤0.22 logMAR was maintained in 50% of studied subjects until age 33.9; legal blindness based on loss of acuity (≥1.00 logMAR) or loss of field (≤20°) was reached at a median age of 40.6 years. Three distinct patterns were observed on FAF imaging: 13 of 22 patients tested had relatively preserved foveal autofluorescence surrounded by a ring of high density, 4 of 22 had increased signal in the fovea with no obvious hyperautofluorescent ring, and 5 of 22 had widespread hypoautofluorescence corresponding to retinal pigment epithelial atrophy. Despite a number of cases presenting with a milder phenotype, there seemed to be no obvious genotype–phenotype correlation. Conclusions MYO7A -related ocular disease is variable. Central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Distinct phenotypic subsets were identified on FAF imaging. A specific allele, previously reported in nonsyndromic deafness, may be associated with a mild retinopathy.