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).

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

References

Shimizu S, Krafchak C, Fuse N, Epstein MP, Schteingart MT, Sugar A, Eibschitz-Tsimhoni M, Downs CA, Rozsa F, Trager EH, Reed DM, Boehnke M, Moroi SE, Richards JE. A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10. Am J Med Genet A. 2004 Nov 1;130A(4):372-7.

PubMedID: 15384081

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.

PubMedID: 165384081

Riazuddin SA, Zaghloul NA, Al-Saif A, Davey L, Diplas BH, Meadows DN, Eghrari AO, Minear MA, Li YJ, Klintworth GK, Afshari N, Gregory SG, Gottsch JD, Katsanis N. Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact with FCD4 on chromosome 9p. Am J Hum Genet. 2010 Jan;86(1):45-53.

PubMedID: 20036349