Phenotype-genotype correlations and emerging pathways in ocular anterior segment dysgenesis

Abstract

Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, as well as syndromal associations. These conditions have a significant impact on vision due to disruption of the visual axis, and also secondary glaucoma which occurs in over 50% of patients. Ocular anterior segment disorders occur due to a complex interplay of developmental, embryological and genetic factors, and often have phenotypic overlaps and genetic heterogeneity. Here we present a review of the clinical features and genes associated with aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, and syndromic forms of these conditions. We also highlight phenotype-genotype correlations, recent discoveries with next-generation sequencing which broaden known phenotypes, and new anterior segment genes and pathways. We provide a guide towards genetic diagnosis for clinicians investigating patients with anterior segment dysgenesis.