COL8A2

Corneal Dystrophy, Posterior Polymorphous 2

Clinical Characteristics
Ocular Features: 

This is primarily a disease of the posterior cornea although the secondary edema may extend to the epithelium.  The disease may be apparent at birth or shortly thereafter by the presence of excrescences or nodules in the endothelial layer with stromal edema.  Descemet membrane can be highly irregular in thickness.  The endothelial cells in PPCD may acquire some characteristics of epithelial cells.

Systemic Features: 

No systemic abnormalities have been reported for PPCD2.

Genetics

This is a rare autosomal dominant disorder and few families have been reported.  The mutant gene, COL8A2 (1p34.3-p32.3) is the same as that causing early onset Fuchs endothelial dystrophy (136800) and both dystrophies have been described in the same family.   The mutation alters the synthesis of alpha 2 chains, part of type VIII collagen, a major component of the Descemet membrance.

For other forms of posterior polymorphous corneal dystrophy, see PPCD3 (609141), and PPPCD1 (122000).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Corneal transplantation may be indicated by the third decade or later.  The corneal lesions tend to recur, however.

References
Article Title: 

Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy

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: 
11689488

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 Fuchs 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.

Genetics

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.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Corneal transplantation is the treatment of choice for advanced disease.

References
Article Title: 

Missense mutations in COL8A2,the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy

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: 
11689488

Inheritance of Fuchs' combined dystrophy

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

PubMed ID: 
399801
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