Background: Advances in genomics continue to enable the discovery of gene variants which cause various inherited ophthalmic
disorders. Several case reports have shown an association between keratoconus and retinal disease but whether there is a genetic
basis for this is still not known.
Methods: Clinical case study with Pentacam imaging, fundus autofluorescence (FAF), macular optical coherence tomography
(OCT), electrophysiology studies, and genetic analysis.
Results: We report three brothers, two of whom have keratoconus and one who was found to have bilateral cone-rod dystrophy.
This was supported by color vision and electrophysiology testing, fundus autofluorescence, and macular OCT findings. Genomic
data analysis revealed three rare gene variants (MAP3K19, ADGRV1, and PIK3CG) common to the brother with cone-rod dystrophy
and one brother with keratoconus. There was also a very significant variant in the CHST6 gene in the latter. Whole exome sequencing
data revealed a rare missense variant for IMPG2 gene in both brothers.
Conclusion: Among the four genes with shared mutations in two of the brothers, IMPG2 has been linked to retinal disease while
MAP3K19 and PIK3CG carry high risk scores for keratoconus pathogenesis. A highly damaging CHST6 variant detected in the brother
with keratoconus is known to cause macular corneal dystrophy and corneal thinning. This study offers the first familial genetic
analysis for keratoconus and cone-rod dystrophy. More studies with genomic investigations are needed in order to further elucidate
the possible relationship between these two diseases.