Clinical Features and Genetic Findings of Autosomal Recessive Bestrophinopathy

Abstract

Autosomal recessive bestrophinopathy (ARB) is a rare subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene. ARB is characterized by multifocal subretinal deposits accompanied by macular edema or subretinal fluid, hyperopia, co-existing narrow angle, and a marked decrease in electrooculogram. However, little is known about the genetic variants and specific clinical features of ARB. This is an observational case series of patients with a clinical and genetic diagnosis of ARB who underwent multimodal imaging. We describe ten patients from nine unrelated families with six known variants and three novel missense variants: c.236C→T, p.(Ser79Phe); C.452C→T, p.(Leu151Pro); and c.650C→T, p.(Trp217Met). The most common variant was c.584C→T, p.(Ala195Val), observed in six patients, without correlation to the severity of the phenotype. All patients manifested bilateral multifocal subretinal deposits and subretinal fluid throughout the follow-up period, while intraretinal fluid was found in approximately half of the eyes. The extent or chronicity of the fluid collection did not correlate with visual acuity. Angle-closure glaucoma was present in five eyes. Three patients had a genetically confirmed family history of ARB, and one patient had a clinically suspected family history. This study reveals novel mutations in the BEST1 gene and adds to the spectrum of clinical presentations of ARB.