We were very interested to read of a second mutation in the seed region of miR-184 resulting in EDICT syndrome.
1 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.
2 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.
3 Similarly, the occurrence of keratoglobus with a corneal endothelial disease, posterior polymorphous corneal dystrophy, has also been recognized.
4
Histopathologic studies of advanced keratoconus are very similar to those of keratoglobus.
5 Biochemical analyses also reveal that a decreased expression of α1 proteinase inhibitor and upregulation of transcription factor Sp1 are common to both.
5 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.
6
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?