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Abstract #122810 Published in IGR 25-1
Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms
Reis LM; Seese SE; Costakos D; Semina EVProgress in Retinal and Eye Research 2024; 102: 101288
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.
Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. Electronic address: lreis@mcw.edu.
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