Genotype-phenotype correlations of ocular posterior segment abnormalities in Marfan syndrome

Purpose Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene. In addition to typical phenotypes such as ectopia lentis and aortic dilation, MFS patients are prone to ocular posterior segment abnormalities, including retinal detachment, maculopathy, and posterior staphyloma. This study aims to investigate the correlations between FBN1 genotype and posterior segment abnormalities within a Chinese cohort of MFS. Design Retrospective study. Participants 121 eyes of 121 patients with confirmed FBN1 mutations between January 2015 and May 2023 were included. Methods Comprehensive ophthalmological exam findings were reviewed, and the incidence of retinal detachment, atrophic / tractional / neovascular maculopathy (ATN classification system) and posterior staphyloma was analyzed between different genotype groups. Only the more severely affected eye from each patient was included. Main outcome measures Clinical features and risk factors. Results Out of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including retinal detachment (4, 3.31%), maculopathy (47, 38.84%), and posterior staphyloma (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients below 20 years old. The location and region of mutations were found to be associated with the incidence of maculopathy (P = 0.013, P = 0.033) and posterior staphyloma (P = 0.043, P = 0.036). Mutations in the middle region had a lower incidence of maculopathy and posterior staphyloma (P = 0.028 and P = 0.006, respectively) than those in C-terminal region. Mutations in the TGF-β regulating sequence exhibited a higher incidence of maculopathy and posterior staphyloma (P = 0.020, P = 0.040). Importantly, the location and region of mutations were also associated with the incidence of atrophic maculopathy (P = 0.013 and P = 0.033, respectively). Mutations in the middle region had a significantly lower probability of atrophic maculopathy (P = 0.006), while mutations in the TGF-β regulating sequence had a higher incidence of atrophic maculopathy (P = 0.020). Conclusion Maculopathy and posterior staphyloma were associated with the location and region of FBN1 mutations. Patients with mutations in the TGF-β regulating sequence faced an increased risk of developing retinopathy.