Keratoconus 8

Description

Keratoconus is a noninflammatory disorder in which there is thinning and ectasia of the cornea. The estimated prevalence varies from 29 to 86 per 100,000, although the condition may be underreported. The onset of disease is typically after puberty, with subsequent progression at a variable rate over the following decades. Visual acuity is initially reduced by irregular corneal astigmatism but scarring can also develop (summary by Liskova et al., 2010).

For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300).

Clinical Features

Liskova et al. (2010) studied 21 individuals with keratoconus from 6 pedigrees of various ethnic and racial backgrounds. All 21 family members designated as affected had clinical confirmation of keratoconus based on slit-lamp biomicroscopy, with the presence in at least 1 eye of 1 or more of the characteristic clinical signs such as central corneal thinning, corneal ectasia, Fleischer ring, Vogt striae, and/or anterior stromal scar of the central cornea. Where image capture was not precluded by extensive scarring, keratoconus was confirmed by videokeratography and pachymetry.

Mapping

Liskova et al. (2010) performed genomewide linkage analysis using DNA samples from 21 affected and 14 unaffected individuals from 6 keratoconus pedigrees and observed the strongest linkage between markers rs1074501 and rs755212 at chromosome 14q24.3. Identical lod scores of 3.58 were obtained for both markers under a dominant model of inheritance; the authors noted that because the markers are only 2.8 Mb apart, it is likely that they indicate the same linked gene. Lod scores greater than 3 were also obtained for a locus on chromosome 6, but Liskova et al. (2010) stated that the contribution to disease in this sample from that locus was only 1.5%, compared to 20.77% from the locus at 14q24.3.

Molecular Genetics

Exclusion Studies

In 6 pedigrees with keratoconus mapping to chromosome 14q24.3, Liskova et al. (2010) sequenced the coding region of the positional and functional candidate gene VSX2 (CHX10; 142993) but did not detect a sequence alteration that segregated with disease in any of the families.