Cysteine Substitution and Calcium-Binding Mutations in FBN1 cbEGF-Like Domains Are Associated With Severe Ocular Involvement in Patients With Congenital Ectopia Lentis

Abstract

Purpose: To investigate the clinical manifestations of congenital ectopia lentis (CEL) in patients with fibrillin (FBN1) calcium-binding epidermal growth factor (cbEGF)-like mutations.Design: Retrospective cohort study.Methods: Consecutive 68 CEL probands with FBN1 cbEGF-like mutations were recruited, mostly comprising Marfan syndrome (MFS) patients. Patients were classified into the cysteine group (n = 43), calcium (Ca2+)-binding group (n = 13) or the others (n = 12) according to their genotypes. Ocular biometrics, morbidities and visual performance were compared among different mutation groups. Linear regression was used to evaluate the risk factors for axial length (AL) elongation.Results: With age-adjustment, cysteine substitution and Ca2+-binding mutations positively contributed to AL elongation (standardized coefficient: 0.410 and 0.367, p = 0.008 and 0.017, respectively). In addition, cataract formation was more frequently detected in patients with Ca2+-binding mutations (observed n = 3, expected n = 1.0; p = 0.036). Patients with cysteine substitutions had the poorest preoperative visual acuity among the three groups (p = 0.012) and did not recover as well as other patients. More MFS diagnoses were made in patients with cysteine substitutions (observed n = 16, expected n = 12.6), while ectopia lentis syndrome was detected more often in patients with cbEGF-like mutations out of the functional regions (observed n = 6, expected n = 2.5; p = 0.023).Conclusion: Compared with patients with cbEGF-like mutations out of functional regions, patients with cysteine substitutions or Ca2+-binding mutations had longer ALs with age adjustment, poorer ocular involvement, visual performance, and systematic manifestations.