The Genetics of Keratoconus: A Review

Abstract

Keratoconus is the most common ectatic disorder of the corneal. Genetic and environmental factors may contribute to its pathogenesis. The focus of this article is to summarize current research into the complex genetics of keratoconus. We discuss the evidence of genetic etiology including family-based linkage studies, twin studies, genetic mutations, and genome-wide association studies. The genes implicated potentially include VSX1, miR-184, DOCK9, SOD1, RAB3GAP1, and HGF. Besides the coding mutations, we also highlight the potential contribution of DNA copy number variants in the pathogenesis of keratoconus. Finally, we present future directions for genetic research in the understanding of the complex genetics of keratoconus and its clinical significance. As new functional, candidate genes for keratoconus are being discovered at a rapid pace, the molecular genetic mechanisms underlying keratoconus pathogenesis will advance our understanding of keratoconus and promote the development of a novel therapy.

Keywords: Association; Cornea; DOCK9; GWAS; Genetics; Keratoconus; Linkage; VSX1; miR-184.

Figure 1

Vogt’s Striae Sign. Vertical lines in Descemet’s membrane are observed.

Figure 2

Munson’s sign.Cone is noted on the lower eyelid on the downgaze.

Figure 3

Corneal Hydrops. Breaks in Descemet’s membrane in severe keratoconus cause acute stromal edema and scarring.

Figure 4

Corneal topography map in advanced keratoconus of left eye (OS for oculus sinister). Blue color indicates areas of fattest curvature. Red indicates the steepest curvature, which is the area with irregular protruding cone, a common feature of keratoconus.