Common Genetic Mutations Found Among Patients With Congenital Ectopia Lentis

Photo of female doctor ophthalmologist is checking the eye vision of young man in modern clinic.
Researchers establish a new diagnostic strategy for subtypes of the pupil defect.

Fibrillin-1 (FBN1) mutations are the most common cause of congenital ectopia lentis (EL), according to the findings of a Chinese study published in the American Journal of Ophthalmology.

Proband cases (n=175) and family controls (n=338) were enrolled at the Eye and ENT Hospital of Fudan University in China between 2016 and 2021. All patients underwent eye examination and exonic sequencing of 289 genes associated with common heritable eye diseases. Clinical and genetic biomarkers for EL were assessed.

Most variants identified in this study (92.57%) were located in 6 genes: FBN1 (83.43%), C3- and PZP-like α-2-macroglobulin domain containing 8 (CPAMD8; 1.71%), collagen type IV α-5 chain (COL4A5; 0.57%), ADAMTS-like 4 (ADAMTSL4; 3.43%), latent transforming growth factor β-binding protein 2 (LTBP2; 1.71%), and cystathionine β-synthase (CBS; 2.29%).

Of the 175 probands, 146 had FBN1 mutations and 83.56% were pathogenic.

The patient group was subdivided into those with Marfan syndrome (MFS; n=31) and those with EL syndrome (ELS; n=24). These groups differed significantly by sex (P =.003), FBN1 mutation location (P <.001), anterior mean keratometry (P =.022), anterior corneal astigmatism (P=.032), and mean keratometry total corneal refractive power (P =.028).

Stratified by FBN1 mutation status, more men had a mutation than women (P =.033). Patients with a mutation also had less severe lens subluxation (P <.001), smaller mean keratometry anterior (P <.001), and smaller mean keratometry total corneal refractive power.

Receiver operating characteristic (ROC) curve analyses found that mean keratometry total corneal refractive power distinguished between patients with and without FBN1 mutations (area under the curve [AUC], 0.688)

On the basis of these observations, the study investigators proposed a diagnostic strategy. Among those with FBN1 mutation, 16.44% were diagnosed with ELS and 2.13% with MFS. This strategy increased the diagnostic rate from 19.43% to 40.57%. The remaining patients can not be diagnosed until they complete cardiovascular development at the age of 20 years.

These findings may not be generalizable to a population outside of China, according to the researchers.

The study authors concluded that congenital EL can present alone or as part of MFS or ELS. Considering genetic and clinical characteristics likely allows for more prompt diagnosis among some patients.


Chen T-H, Chen Z-X, Zhang M, et al. Combination of panel-based next-generation sequencing and clinical findings in congenital ectopia lentis diagnosed in Chinese patients. Am J Ophthalmol. 2021;S0002-9394(21)00593-6. doi:10.1016/j.ajo.2021.11.014