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COL8A2 codes for the alpha 2 chains of VIII collagen, a major component of the Descemet membrane.
COL8A2 codes for the alpha 2 chains of VIII collagen, a major component of the Descemet membrane.

Corneal Dystrophy, Fuchs Endothelial, Early Onset

Clinical Characteristics

Ocular Features

This is one of several adult onset corneal endothelial dystrophy (see Fuchs’ endothelial corneal dystrophy, late onset, (610158) for more forms of adult Fuchs’ endothelial dystrophy).  The onset of this type is considerably earlier than in the more common adult onset type (610158) .  Endothelial disease has been noted as early as three years of age but onset is likely later than in the congenital forms (CHED1; 121700), (CHED2; 217700).  In early onset Fuch’s dystrophy, most individuals have evident disease by the third and fourth decades and many have advanced disease by the fourth and fifth decades.  The sex ratio among affected individuals is closer to 1:1 in this disorder compared with the more common adult onset type in which the disease is more common in females.

In this early onset disorder the guttae are small and more rounded than those in the later onset endothelial dystrophies, and are closer to the center of the endothelial cells.  The progression of corneal decompensation is temporally similar to that of the late onset dystrophies, resulting in clinically advanced disease within 3 to 4 decades.  The progression of disease has been documented through quantifying the number of guttae over time.   Among 26 patients, the number increased as much as 29.1% over a 30 month period, and an exponential increase was noted after age 50 years.  The inferotemporal quadrant of the cornea had the greatest proportion of guttae.  As in other forms of endothelial corneal dystrophy, Descement’s  membrane is thickened and exhibits nodularity with secondary apoptosis of endothelial cells.

Systemic Features

None have been reported.


A mutation in the COL8A2 gene, L450W, located on chromosome 1 (1p34.3-p32.3) seems to be responsible for this disease.  The gene codes for the alpha-2 chain of collagen VIII which is an important component of Descemet’s membrane.  Like many other collagen diseases, this disorder is transmitted as an autosomal dominant.

This gene is also mutant in posterior polymorphous corneal dystrophy 2 (609140) and both types of dystrophy have been reported in the same family suggesting they may be the same disorder with variable expressivity.

Treatment Options

Corneal transplantation is the treatment of choice for advanced disease.


Meadows DN, Eghrari AO, Riazuddin SA, Emmert DG, Katsanis N, Gottsch JD. Progression of Fuchs corneal dystrophy in a family linked to the FCD1 locus. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5662-6.

PubMed ID: 

Wang Z, Handa JT, Green WR, Stark WJ, Weinberg RS, Jun AS. Advanced glycation end products and receptors in Fuchs' dystrophy corneas undergoing Descemet's stripping with endothelial keratoplasty. Ophthalmology. 2007 Aug;114(8):1453-60.

PubMed ID: 

Gottsch JD, Sundin OH, Liu SH, Jun AS, Broman KW, Stark WJ, Vito EC, Narang AK, Thompson JM, Magovern M. Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs’ corneal dystrophy. Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1934-9.

PubMed ID: 

Biswas S, Munier FL, Yardley J, Hart-Holden N, Perveen R, Cousin P, Sutphin JE, Noble B, Batterbury M, Kielty C, Hackett A, Bonshek R, Ridgway A, McLeod D,Sheffield VC, Stone EM, Schorderet DF, Black GC. Missense mutations in COL8A2,the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum Mol Genet. 2001 Oct 1;10(21):2415-23.

PubMed ID: 

Magovern M, Beauchamp GR, McTigue JW, Fine BS, Baumiller RC. Inheritance of Fuchs' combined dystrophy. Ophthalmology. 1979 Oct;86(10):1897-923.

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