Genetics of the corneal endothelial dystrophies: an evidence-based review

• Published in: Clinical genetics Vol. 84; no. 2; pp. 109 - 119
• Main Authors: Aldave, A J, Han, J, Frausto, R F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2013
• Subjects: Corneal Dystrophies, Hereditary - diagnosis; Corneal Dystrophies, Hereditary - genetics; corneal dystrophy; corneal dystrophy, Fuchs endothelial, 1; corneal dystrophy, Fuchs endothelial, 2; corneal dystrophy, Fuchs endothelial, early onset; corneal dystrophy, Fuchs endothelial, late onset; corneal dystrophy, posterior polymorphous, 1; corneal dystrophy, posterior polymorphous, 2; corneal dystrophy, posterior polymorphous, 3; corneal endothelial dystrophy 1; corneal endothelial dystrophy 2; early onset; Evidence-Based Medicine; Eye diseases; Fuchs endothelial; Genetic disorders; Humans; late onset; Ophthalmology; posterior polymorphous; corneal dystrophy, Fuchs endothelial, 2; corneal dystrophy, Fuchs endothelial, early onset; corneal dystrophy, Fuchs endothelial, 1; corneal endothelial dystrophy 1; corneal dystrophy, Fuchs endothelial, late onset; corneal endothelial dystrophy 2; corneal dystrophy, posterior polymorphous, 2; corneal dystrophy, posterior polymorphous, 3; corneal dystrophy, posterior polymorphous, 1
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12191

The aim of this review was to provide an evidenced‐based review of the genetic basis of the corneal endothelial dystrophies. A review of the English language peer‐reviewed literature describing the molecular genetic basis of posterior polymorphous corneal dystrophy (PPCD), congenital hereditary endothelial dystrophy (CHED), Fuchs endothelial corneal dystrophy (FECD) and X‐linked endothelial corneal dystrophy (XECD) was performed. Mutations in several genes have been implicated as playing a pathogenic role in the corneal endothelial dystrophies: VSX1 mutations in PPCD1; COL8A2 mutations in PPCD2 and FECD; ZEB1 mutations in PPCD3 and FECD; and SLC4A11 mutations in CHED2 and FECD. However, linkage, association and familial segregation analyses support a role of only one gene in each corneal endothelial dystrophy: ZEB1 in PPCD3, SLC4A11 in CHED2 and COL8A2 in FECD (early onset). In addition, insufficient evidence exists to consider the autosomal dominant form of CHED (CHED1) as distinct from PPCD. An accurate classification of the corneal endothelial dystrophies requires a critical review of the evidence to support the role of each suggested chromosomal locus, gene and genetic mutation associated with a corneal endothelial dystrophy. Only after the separation of evidence from opinion is performed can a critical examination of the molecular pathways that lead to endothelial dysfunction in each of these disorders be accurately performed.