Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.

Hassan Khojasteh,Fatemeh Suri,Hamid Ahmadieh,Narges Hassanpoor,Alireza Khodabande,Hooshang Faghihi,Mohsen Azarmina,Narsis Daftarian,Masoud Reza Manaviat,Fatemeh Bazvand,Hamid Riazi-Esfahani,Nazanin Ebrahimiadib,Afrooz Moghaddasi,Houra Naraghi,Hamideh Sabbaghi,Alessandro Meduri

doi:10.1155/2021/6674290

Abstract

Background To describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series. Methods Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients. Results The age at onset was 4–35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies. Conclusions ARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB.

Highlights

Bestrophin-1 (BEST1) gene mutations may cause a variety of ocular phenotypes called “bestrophinopathies.” a variety of clinical presentations have been described in the literature [1], five known bestrophinopathies include autosomal dominant best or best vitelliform macular dystrophy (BVMD), adult-onset vitelliform macular dystrophy (AVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), autosomal recessive bestrophinopathy (ARB), and retinitis pigmentosa (RP)
Four patients showed subretinal fibrosis in the foveal or parafoveal region without any evidence of previous choroidal neovascularization (CNV); based on optical coherence tomography (OCT), three of them were compatible with fibrotic pillars (patients 4, 15, and 21; Figures 2(g) and 2(i))
Luo et al described clinical manifestations and novel genetic mutations in 21 ARB-diagnosed patients in the Chinese population [4] and reported 20 patients with serous retinal detachments, which correlates with our data (48 eyes, 95%). ey reported fine peripheral leakage on fluorescein angiography (FA) in 47% of patients, while this was observed in only four patients in our study

Summary

Introduction

Bestrophin-1 (BEST1) gene mutations may cause a variety of ocular phenotypes called “bestrophinopathies.” a variety of clinical presentations have been described in the literature [1], five known bestrophinopathies include autosomal dominant best or best vitelliform macular dystrophy (BVMD), adult-onset vitelliform macular dystrophy (AVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), autosomal recessive bestrophinopathy (ARB), and retinitis pigmentosa (RP). Shallow anterior segment, angle-closure glaucoma, abnormal or subnormal full-field electroretinography (ERG) (in contrast to normal ERG in BVMD), intraretinal cystic changes, and concurrent subretinal fluid can be seen in ARB [1,2,3,4,5,6]. Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Our study expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB

Methods

Results

Conclusion