Corneal thinning phenotypes: an alternative perspective.

We were very interested to read of a second mutation in the seed region of miR-184 resulting in EDICT syndrome. We were unsure after reading the paper, however, of how the corneal findings should be classified and of the statement that the family “does not demonstrate a keratoconus phenotype.” Keratoconus, the commonest disorder of corneal thinning and steepening, has been linked with VSX1 and SOD1 in single studies and up to 14 different genetic loci. It has a variable phenotype, and while few would dispute the diagnosis in classic cases with central corneal thinning, identifying variants such as forme fruste disease (where a cone may not be present) may be more challenging. A less common disorder of corneal thinning is keratoglobus, in which the thinning is global and often most pronounced in the periphery. Iris hypoplasia with keratoglobus has been described. Similarly, the occurrence of keratoglobus with a corneal endothelial disease, posterior polymorphous corneal dystrophy, has also been recognized. Histopathologic studies of advanced keratoconus are very similar to those of keratoglobus. Biochemical analyses also reveal that a decreased expression of 1 proteinase inhibitor and upregulation of transcription factor Sp1 are common to both. Disorders of retinal development (as found in 4 of 10 EDICT patients) can also co-segregate with corneal ectasia; CRB1 mutations causing Leber congenital amaurosis (LCA) have been associated with both keratoconus and keratoglobus. We wonder if the reported corneal phenotype in EDICT syndrome should fall within the keratoconus/-globus spectrum and, as such, should be considered a candidate gene for these as well as other “cornea plus” syndromes? Osama Giasin Rehna S. Khan Kamron Khan