Genetics of the corneal dystrophies: what we have learned in the past twenty-five years

Cornea. 2000 Sep;19(5):699-711. doi: 10.1097/00003226-200009000-00015.


Purpose: To indicate important changes in our understanding of the corneal dystrophies.

Methods: A review of the literature of the last quarter of a century.

Results: The earliest clinical classifications of the corneal dystrophies were based on the application of clinical, biological, histochemical, and ultrastructural methods. Since then, the first great impetus to our understanding has come from the application of techniques to map disorders to specific chromosome loci, using polymorphic markers. More recently, using candidate gene and related approaches, it has been possible to identify genes causing several of the corneal dystrophies and the mutations responsible for their phenotypic variation. A notable success has been to show that several important "stromal" dystrophies result from mutations in the gene beta ig-h3, which encodes for the protein keratoepithelin (beta ig-h3).

Conclusions: For the corneal dystrophies, as with other inherited disorders, there is room for two sorts of classification system, one based mainly on clinical presentation and the other on an up-to-date understanding of the genetic mechanisms. They are not mutually exclusive. Some developmental corneal disorders are also discussed.

Publication types

  • Review

MeSH terms

  • Cornea / metabolism
  • Cornea / pathology
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / metabolism
  • Corneal Dystrophies, Hereditary / pathology
  • Extracellular Matrix Proteins*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Phenotype
  • Repressor Proteins
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Extracellular Matrix Proteins
  • Eye Proteins
  • Genetic Markers
  • Homeodomain Proteins
  • Neoplasm Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein