Keratoconus and Cone-Rod Dystrophy among Brothers: Clinical Case Study and Genetic Analysis

Volume 2 - Issue 2

Victoria Dimacali^1*, Spyridon Koronis¹, Stavrenia Koukoula¹, Achilleas Rasoglou², Aspasia Adamopoulou¹, Elissavet Siskou³ and Miltos Balidis¹

Received: March 25, 2019;   Published: April 01, 2019

DOI: 10.32474/TOOAJ.2018.02.000133

Full Text PDF

To view the Full Article   Peer-reviewed Article PDF

Abstract

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.

Keywords: keratoconus, Cone-rod dystrophy, Autofluorescence, Electrophysiology, Genetic testing

Abstract| Introduction| Case Report| Discussion| References|