Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts

Am J Ophthalmol. 2024 Jan 5:263:206-213. doi: 10.1016/j.ajo.2023.10.022. Online ahead of print.

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 postoperative 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 patients with unrelated congenital cataract.

Interventions: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants.

Main outcomes and measures: factors related to the genetic diagnosis yield of syndromic congenital cataracts.

Results: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A 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 whole-exome sequencing helps 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.