Early Diagnosis of syndromic congenital cataracts in a Large Cohort of Congenital Cataracts

Abstract

Purpose

To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients.

Design

Prospective cohort study.

Methods

Setting: The participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre-and post-operative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. Participants: 115 unrelated congenital cataract patients. Interventions: performing clinical examinations, whole-exome sequencing (WES) and bioinformatics analysis for all participants. Main outcomes and measures: Factors related to genetic diagnosis yield of syndromic congenital cataracts.

Results

Bilaterally asymmetrical cataracts were identified associating with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. 34.8% of the probands were early diagnosed as various syndromes with the help of genetic information. Phenotype-genotype correlation was detected for some genes and deep phenotypes.

Conclusions

We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of WES help provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.