Clinical and Surgical Implications of Genotype-Phenotype Correlations in Congenital Ectopia Lentis: A Real-World...

To characterize the genetic landscape of congenital ectopia lentis (EL) and assess genotype-phenotype correlations with implications for surgical decision-making.

This retrospective study enrolled patients with congenital EL who presented to Fudan University Eye and ENT Hospital between 2017 and 2025. We performed targeted next-generation sequencing for probands, with candidate variants confirmed by Sanger sequencing. Patients were categorized into FBN1 and non-FBN1 groups. The ocular features and surgical options were compared across genotypes.

A total of 497 probands were enrolled. The molecular diagnostic yield was 93.36%, with FBN1 variants accounting for 82.93% and non-FBN1 variants for 10.44%. Compared with FBN1 cases, non-FBN1 patients exhibited higher EL severity (P < 0.001), lower corneal curvature radius (CCR) (P < 0.001), and higher incidence of ocular comorbidities (P < 0.01). Surgically, non-FBN1 patients more often required robust intraocular lens fixation methods than did FBN1 patients (P < 0.001). Within the FBN1 cohort, the DN(Cys+CaB)+HI subgroup exhibited longer axial length (AL) (P < 0.001), thinner central corneal thickness (CCT) (P = 0.015), and a higher proportion of clinically diagnosed Marfan syndrome (P < 0.001) compared with the DN(Others) subgroup. In contrast, the FBN1 DN(Others) subgroup showed comparable AL, CCT, and CCR to the non-FBN1 group (all P > 0.05). No significant difference of ocular biometrics or surgical options were observed within the non-FBN1 group, except for the highest CCR in patients harboring CPAMD8 variants (P = 0.004).

Genetic characterization of congenital EL extends beyond diagnosis to inform ocular phenotype variability and surgical decision-making.