Anterior segment dysgenesis: part II—genetics and pathogenesis

Abstract

ABSTRACT Introduction Anterior segment dysgeneses are congenital anomalies that predominantly involve the cornea, iris, anterior chamber, iridocorneal angle structures, and ciliary body, but may also have posterior segment findings. Genetic causes of these diseases have gradually been identified over the last 30 years. The clinical genetics combined with animal studies have given important insight into the pathogenesis of these diseases. Areas Covered An overview of anterior segment development will be followed by a review of the genetics and pathogenesis underlying primary congenital glaucoma, aniridia, Axenfeld-Rieger syndrome, Peters anomaly, sclerocornea, congenital ectropion uvea, and megalocornea/megalophthalmos. Expert Opinion Lack of genetic testing is a critical barrier for increasing our understanding of these diseases and ultimately improving outcomes. Genetic testing is important for patients and gives greater insight into genotype–phenotype correlations regarding treatments and prognosis. Nevertheless, there is a significant percentage of patients with no identified genetic cause. This demonstrates the great opportunity for gene discovery, which requires wider access to whole-genome sequencing and increased support for research efforts and funding. The increased knowledge of genetics and basic science will ultimately lead to the development of novel molecularly targeted treatments.