Sector Retinitis Pigmentosa: Extending the Molecular Genetics Basis and Elucidating the Natural History

Abstract

Purpose To determine the genetic background of sector retinitis pigmentosa (RP) natural history to better inform patient counseling. Design Retrospective case series. Methods Review of clinical notes, retinal imaging including color fundus photography (CFP), fundus autofluorescence (FAF), optical coherence tomography (OCT), electrophysiological assessment (ERG), and molecular genetic testing were performed in patients with sector RP from a single tertiary referral center. Main outcomes measured were demographic data, signs and symptoms, visual acuity, molecular genetics; and ERG, FAF, and OCT findings. Results Twenty-six molecularly confirmed patients from 23 different families were identified harboring likely disease-causing variants in 9 genes. The modes of inheritance were autosomal recessive (AR, n=6: USH1C , n=2; MYO7A , n=2; CDH3 , n=1; EYS , n=1), X-linked (XL, n=4: PRPS1 , n=1; RPGR , n=3), and autosomal dominant (AD, n=16: IMPDH1 , n=3; RP1 , n=3; RHO , n=10), with a mean age of disease onset of 38.5, 30.5, and 39.0 years old, respectively. Five of these genes have not previously been reported to cause sector RP ( PRPS1 , MYO7A , EYS , IMPDH1 , and RP1). Inferior and nasal predilection was common across the different genotypes, and patients tended to maintain good central vision. Progression on serial FAF was observed in RPGR , MYO7A , CDH23 , EYS , IMPDH1 , RP1 , and RHO -associated sector RP. Conclusions The genotypic spectrum of the disease is broader than previously reported. The longitudinal data provided will help to make accurate patient prognoses and counseling as well as inform patients' potential participation in the increasing numbers of trials of novel therapeutics and access to future treatments.

Inherited retinal diseases: Therapeutics, clinical trials and end points—A review

“…Rhodopsin ( RHO , OMIM 180380) can cause a range of (RCD) phenotypes, including typical RCD, sector RP, pericentral RP and CSNB 116 . The severity of RHO ‐associated phenotypes varies significantly, from asymptomatic to severe disease.…”

Stationary and Progressive Phenotypes Caused by the p.G90D Mutation in Rhodopsin Gene

“…Sector RP is an uncharacteristic form of RP where only one or two quadrants of the retina are affected, in most cases inferior or nasal parts of the retina (superior visual field defects) possibly due to greater UV light exposure [ 25 , 39 ]. Sector RP has a favorable visual prognosis compared to generalized RP; it has been reported that 82% of cases will retain a visual acuity (VA) of 20/40 or better [ 39 ]. Generally, it is therefore considered a stationary to slowly progressive disease but may eventually lead to a more severe, diffuse RP phenotype [ 40 ].…”

Beyond Sector Retinitis Pigmentosa: Expanding the Phenotype and Natural History of the Rhodopsin Gene Codon 106 Mutation (Gly-to-Arg) in Autosomal Dominant Retinitis Pigmentosa

“…Our study includes three cases with long-term re-assessment, including one patient evaluated after more than 30 years of disease, which clearly demonstrates the evolution in her clinical and electrophysiologic findings. A recent study of the etiology of sector RP across a variety of genotypes was conducted by Georgiou et al [ 19 ], including RHO variants, and suggested that any progression that was noted up to 6 years of follow-up was small in extent with little clinical impact. While we agree with the authors’ conclusion that the long-term prognosis for central visual acuity is good in many of these patients, significant progression in the disease with clinical and functional impact on peripheral vision can occur over longer periods in RHO p.Gly106Arg disease.…”

“…The RHO c.316G > A, p.Gly106Arg variant was first described as a cause of autosomal dominant sector RP in four patients with a distinct phenotype characterized by pigmentary changes in the inferior retina and corresponding visual field impairment in the superior hemisphere [18], with a good central visual prognosis. This inferior sectoral phenotype was subsequently seen in five other patients [19,21,22], including three from the same family [21]. A careful review of the reported cases, however, shows that at least one of these patients had more extensive near-peripheral anatomic involvement and evidence of a pericentral ring scotoma on visual fields [21].…”

“…Even the most common p.Pro23His mutation responsible for RHO -associated ADRP has shown regional phenotypes [ 9 ]. Recently, Georgiou and colleagues undertook a survey of the disease spectrum in molecularly-confirmed cases of sector-like RP [ 19 ], highlighting associated variants in a number of additional genes including RPGR , USH1C , MYO7A, CDH23, EYS , IMPDH1 , RP1 , and RHO . As discussed, while sector RP is generally thought of as a mild phenotype when compared to generalized RP, with a good prognosis for visual acuity in the long-term [ 20 ], there is a lack of natural history and longitudinal data on which to base our expectations of disease progression.…”