endothelial metaplasia

Corneal Dystrophy, Posterior Polymorphous 3

Clinical Characteristics
Ocular Features: 

This is a genetically and clinically heterogeneous type of corneal dystrophy.  Endothelial metaplasia seems to play a role as these cells acquire some characteristics of epithelial cells.  The posterior cornea has guttae and lesions of various sizes surrounded by a grayish halo.  These may become confluent and lead to stromal edema extending into the epithelium.  The thickness of the Descemet membrane is highly variable and a retrocorneal membrane may be present.  Onset is variable as some infants will have corneal edema whereas many, if not most, adults are asymptomatic.  The condition in severely affected children may resemble congenital hereditary corneal dystrophy.

Systemic Features: 

No consistent systemic abnormalities have been reported.  However, some patients have been reported with inguinal hernias, hydroceles, and possible bone abnormalities suggesting that the ZEB1 mutation may have extraocular effects as well.

Genetics

This is an autosomal dominant disorder caused by a mutation in the ZEB1 gene (10p11.2).  Mutations in the same gene have recently been found in some cases with late-onset Fuchs endothelial dystrophy.

For other forms of posterior polymorphous dystrophy see PPCD1 (122000) and PPCD2 (609140).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Most patients do well and require no treatment.  Corneal transplantation may be required for the more severe cases but, as in many dystrophies, the lesions tend to recur in the graft.

References
Article Title: 

Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells

Krafchak CM, Pawar H, Moroi SE, Sugar A, Lichter PR, Mackey DA, Mian S, Nairus T, Elner V, Schteingart MT, Downs CA, Kijek TG, Johnson JM, Trager EH, Rozsa FW, Mandal MN, Epstein MP, Vollrath D, Ayyagari R, Boehnke M, Richards JE. Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells. Am J Hum Genet. 2005 Nov;77(5):694-708.

PubMed ID: 
165384081

Corneal Dystrophy, Posterior Polymorphous 1

Clinical Characteristics
Ocular Features: 

This form of corneal dystrophy is often asymptomatic but some patients experience endothelial decompensation and corneal edema, which may even be seen soon after birth. The edema may extend into the epithelium.  The basic mechanism entails metaplasia of endothelial cells which seem to acquire some characteristics of epithelial cells.  Posterior corneal lesions of variable morphology appear in various patterns and are often surrounded by grayish halos.  When these become confluent the corneal edema is more severe and may resemble a congenital endothelial dystrophy.  The endothelial cell count is often low.  The Descemet layer also becomes abnormal.  The posterior border of the cornea appears nodular and grayish in color, often in a geographic pattern.  Surprisingly, endothelial function often is maintained and patients may remain asymptomatic for many years.

Some patients have features of anterior chamber dysgenesis with iris anomalies, anterior synechiae, and glaucoma.  It is also sometimes confused with EDICT syndrome (614303).

Systemic Features: 

No systemic disease is associated with this disorder.

Genetics

This is a genetically heterogeneous autosomal dominant disorder caused by several mutations including the promotor of OVOL2 at 20p11.23 responsible for PPCD1 described here.  Another locus for this disease has been mapped to 20q11, the same locus responsible for congenital hereditary corneal edema 1 (CHED1) and it is possible that these are allelic or clinical variants of the same mutation.  The latter is made more likely by the fact that both disorders have been found in relatives.  OMIM has combined the entities CHED1 and PPCD1 as a single disorder (122000).

For other forms of posterior polymorphous corneal dystrophy see, PPCD2 (609140) and PPCD3 (609141).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Few patients require treatment since the endothelial changes are frequently stable. Among those that do undergo corneal transplantation, the changes often recur in the donor button.

References
Article Title: 
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