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 fibrillin-1 ( (FBN1). In addition to typical phenotypes such as ectopia lentis (EL) and aortic dilation, patients with MFS are prone to ocular posterior segment abnormalities, including retinal detachment (RD), maculopathy, and posterior staphyloma (PS). This study aims to investigate the correlations between FBN1 genotype and posterior segment abnormalities within a Chinese cohort of MFS.

Design

Retrospective study.

Participants

One hundred twenty-one eyes of 121 patients with confirmed FBN1 mutations between January 2015 and May 2023 were included.

Methods

Comprehensive ophthalmic examination findings were reviewed, and the incidence of RD, atrophic, tractional, and neovascular maculopathy (ATN classification system), and PS 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

Of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including RD (4, 3.31%), maculopathy (47, 38.84%), and PS (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients <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 PS (P = 0.043, P = 0.036). Mutations in the middle region had a lower incidence of maculopathy and PS (P = 0.028 and P = 0.006, respectively) than those in C-terminal region. Mutations in the transforming growth factor-β (TGF-β) regulating sequence exhibited a higher incidence of maculopathy and PS (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 region had a higher incidence of atrophic maculopathy (P = 0.020).

Conclusions

Maculopathy and PS were associated with the location and region of FBN1 mutations. Patients with mutations in the TGF-β regulating region faced an increased risk of developing retinopathy.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.