The spectrum of genetic mutations in patients with asymptomatic mild familial exudative vitreoretinopathy

Familial exudative vitreoretinopathy (FEVR) is a disease exhibits a wide range of clinical signs, ranging mild peripheral retinal vascular anomalies to severe retinal detachments. Individuals with mild FEVR are frequently asymptomatic with good visual function and are often undiagnosed. However, little is known about the genetic characters of the cohort. The purpose of this study was to investigate the clinical characteristics and genetic spectrum of in patients with asymptomatic mild FEVR. Herein, sixty-two patients (124 eyes) with asymptomatic mild FEVR were studied in a case series. Comprehensive ophthalmic examinations and genetic testing were performed in all patients. Clinical examinations showed that the avascular zone was seen in all 124 eyes and was the most common abnormality observed. Increased vessel branching and straightened peripheral vessel branches were found in 122 (98.4%) eyes. Late-phase angiographic posterior and peripheral leakage (LAPPEL) was observed in 80 (64.5%) eyes and V-shape degeneration was noted in 36 (29.0%) eyes. Other manifestations including extensive anastomoses, retinal ridges, and extraretinal neovascularization, which were detected in 30 (24.2%), 10 (8.1%) and 2 (1.6%) eyes respectively. Overall, pathogenic mutations were identified in 48.4% (30/62) of individuals with asymptomatic mild FEVR. Mutations in FZD4, LRP5, TSPAN12, and KIF11 were detected in 21.0% (13/62), 12.9% (8/62), 12.9% (8/62), and 1.6% (1/62) of our patients respectively. Ten novel mutations were found. In conclusion: Pathogenic mutations in the known FEVR-associated genes were detected in nearly half (48.4%) of the asymptomatic mild FEVR cohort. Among these mutations, FZD4 was predominant, appearing in 21.0% of all individuals. Patients with asymptomatic mild FEVR should receive timely examinations, lifelong monitoring, and some of them need preventive therapy and treatment. Additionally, we discovered 10 novel variants, which may enable a deeper understanding of this disease.