Heredity of Keratoconus

  • Colin E. WilloughbyEmail author
  • Judith Lechner


Epidemiological, family and twin studies support a role for heredity in the pathogenesis of keratoconus. Candidate gene analysis and genetic mapping have identified a limited number of genetic factors implicated in the development of keratoconus to date. Mutations in the visual system homeobox gene 1 (VSX1) are found in approximately 2–3% of keratoconus cases. As such, VSX1 represents the only major genetic defect identified to date causing keratoconus. The role of other candidate genes (SOD1, IL-1 and collagens) has not been firmly established. Most gene mapping studies have been performed on Caucasian families with autosomal dominant keratoconus or in isolated populations where genetic heterogeneity is minimised. Multiple loci have been mapped although no pathological mutations have been detected in linked disease intervals. Only the mapped locus on 5q21.2 has been convincingly replicated in two independent datasets. The clinical variability and evidence that keratoconus is linked to multiple chromosomal regions is consistent with an oligogenic or even polygenic model. A genetic model in which mutations in several different genes involved in common pathways cause keratoconus is most likely. Emerging data from genome wide association studies should bring further insights into the genetic basis of keratoconus.


Alport Syndrome Corneal Dystrophy Keratoconus Patient Digenic Inheritance Brittle Cornea Syndrome 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.School of Medicine, Dentistry and Biomedical SciencesCentre for Vision and Vascular Science, Queen’s University Belfast, Royal Victoria HospitalBelfastUK

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