A molecular perspective on corneal dystrophies

Corneal dystrophies refer to a group of corneal diseases and that are genetically determined. These have been traditionally classified with respect to the layer of cornea involved. We now know that this does not reflect the underlying pathobiology. Most of the corneal dystrophies are of Mendelian inheritance with some phenotype diversity and a variable degree of penetrance. The dystrophies involving enzymatic processes tend to be of autosomal recessive inheritance. In some cases, such as keratoconus, the inheritance pattern is not always clear and is considered complex. The age of onset of the disease, as in most inherited eye disorders, is variable and does not reflect the underlying pathogenic defect. Few cases are congenital. Our understanding of corneal dystrophies is undergoing somewhat of a revolution as over 12 chromosomes have been associated with corneal dystrophies with mutations identified in at least 14 genes if one includes anterior segment dysgenesis in this group of conditions. Several dystrophies remain without a gene or a genetic location (locus) and more familial studies are required. The new molecular information is challenging the traditional thinking about these conditions that was usually guided by the histopathological findings. As this new knowledge becomes more refined, the classification of this group of disorders will eventually be revisited to have a molecular basis. The elucidation of the underlying biochemical pathways may allow us to envisage the possibility of modulating these phenotypes in the future