Disease Expression in Autosomal Recessive Retinal Dystrophy Associated With Mutations in the DRAM2 Gene

• Published in: Investigative ophthalmology & visual science 2015-12, Vol.56 (13), p.8083-8090
• Main Authors: Sergouniotis, Panagiotis I, McKibbin, Martin, Robson, Anthony G, Bolz, Hanno J, De Baere, Elfride, Müller, Philipp L, Heller, Raoul, El-Asrag, Mohammed E, Van Schil, Kristof, Plagnol, Vincent, Toomes, Carmel, Ali, Manir, Holder, Graham E, Charbel Issa, Peter, Leroy, Bart P, Inglehearn, Chris F, Webster, Andrew R
• Format: Article
• Language: English
• Subjects: Adult; Disease Progression; Electrophysiology; Female; Fluorescein Angiography; Humans; Male; Membrane Proteins - genetics; Middle Aged; Mutation; Night Blindness - etiology; Night Blindness - physiopathology; Retina - physiopathology; Retinal Dystrophies - genetics; Retinal Dystrophies - physiopathology; Tomography, Optical Coherence; Visual Acuity - physiology; Visual Field Tests; Visual Fields - physiology; Young Adult
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.15-17604

To determine the disease course of retinal dystrophy caused by recessive variants in the DRAM2 (damage-regulated autophagy modulator 2) gene. Sixteen individuals with DRAM2-retinopathy were examined (six families; age range, 19-56 years, includes one pre-symptomatic case). The change in visual acuity over time was studied, and electrophysiology (n = 6), retina-tracking perimetry (n = 1), fundus autofluorescence (FAF) imaging (n = 6), and optical coherence tomography (OCT; n = 12) were performed. All symptomatic patients presented with central visual loss (15/15) unaccompanied either by nyctalopia or light-hypersensitivity; most (11/15) developed symptoms in the third decade of life. A granular macular appearance, often with associated white/yellow dots, was an early fundoscopic feature. There was an ill-defined ring of hyperautofluorescence on FAF. Optical coherence tomography revealed loss of the ellipsoid zone perifoveally in a 19-year-old pre-symptomatic individual. The central atrophic area enlarged over time and fundoscopy showed peripheral degeneration in seven of the nine individuals that were examined ≥ 10 years after becoming symptomatic; some of these subjects developed nyctalopia and light hypersensitivity. Electrophysiology revealed generalized retinal dysfunction in three of the five individuals that were tested ≥ 10 years after becoming symptomatic. Patients with DRAM2-retinopathy are typically asymptomatic in the first two decades of life and present with central visual loss and a maculopathy. A faint hyperautofluorescent ring on FAF can be a suggestive feature. The retinal periphery is frequently affected later in the disease process. Photoreceptor degeneration is likely to be the primary event and future studies on DRAM2-retinopathy are expected to provide important insights into retinal autophagy.