Medical College of Wisconsin
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Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms. Prog Retin Eye Res 2024 Sep;102:101288

Date

08/04/2024

Pubmed ID

39097141

Pubmed Central ID

PMC11392650

DOI

10.1016/j.preteyeres.2024.101288

Scopus ID

2-s2.0-85200800135 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Development of the anterior segment of the eye requires reciprocal sequential interactions between the arising tissues, facilitated by numerous genetic factors. Disruption of any of these processes results in congenital anomalies in the affected tissue(s) leading to anterior segment disorders (ASD) including aniridia, Axenfeld-Rieger anomaly, congenital corneal opacities (Peters anomaly, cornea plana, congenital primary aphakia), and primary congenital glaucoma. Current understanding of the genetic factors involved in ASD remains incomplete, with approximately 50% overall receiving a genetic diagnosis. While some genes are strongly associated with a specific clinical diagnosis, the majority of known factors are linked with highly variable phenotypic presentations, with pathogenic variants in FOXC1, CYP1B1, and PITX2 associated with the broadest spectrum of ASD conditions. This review discusses typical clinical presentations including associated systemic features of various forms of ASD; the latest functional data and genotype-phenotype correlations related to 25 ASD factors including newly identified genes; promising novel candidates; and current and emerging treatments for these complex conditions. Recent developments of interest in the genetics of ASD include identification of phenotypic expansions for several factors, discovery of multiple modes of inheritance for some genes, and novel mechanisms including a growing number of non-coding variants and alleles affecting specific domains/residues and requiring further studies.

Author List

Reis LM, Seese SE, Costakos D, Semina EV

Authors

Deborah M. Costakos BS, MD, MS Special Advisor to the Dean, Professor in the School of Medicine Operations department at Medical College of Wisconsin
Elena V. Semina PhD Chief, Professor in the Ophthalmology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anterior Eye Segment
Eye Abnormalities
Eye Diseases, Hereditary
Genetic Association Studies
Humans
Phenotype