20p11.2-q11.2 locus

Corneal Dystrophy, Congenital Endothelial 1

Clinical Characteristics
Ocular Features: 

(OMIM has combined this disorder with PPCD1 (122000) based on genetic and clinical evidence.)

Early onset limbus-to-limbus corneal clouding is the outstanding feature.  Some asymmetry is often present.  Vision is minimally impaired if at all in many children but slow progression occurs and adults often become visually impaired.  Nystagmus does not develop.  Photophobia and tearing are common.  The corneal appearance can lead to the erroneous diagnosis of congenital glaucoma.  However, some infants actually do have congenital glaucoma as well leading some to suggest this may be a disorder of anterior chamber dysgenesis.  The edematous cornea may be of 2-3 times normal thickness.  It may appear generally hazy and sometimes has a diffuse ground glass appearance.  

The posterior surface often appears mottled and has been described as having a peau d'orange appearance.  The endothelium is attenuated or even absent histologically and abnormal, disorganized collagen fibrils have been found in a thickened Descemet layer by electron microscopy.  The remaining endothelial cells are often vacuolated and heaped in double layers, with some containing melanin granules.  Some atrophy and edema of the epithelium with partial loss of Bowman's can be seen histologically.

Systemic Features: 

No systemic abnormalities are found in this disorder.

Genetics

This is an autosomal dominant disorder that maps to a locus on chromosome 20 (20p11.2-q11.2).   The molecular defect seems to involve the promotor of OVOL2 (20p11.23).  It is of interest that the posterior polymorphous corneal dystrophy 1 (PPCD1, 122000) mutation has been mapped to the same pericentric region, and it has been suggested that the two conditions may be allelic. These are now combined into a single entity in OMIM. 

This disorder should not be confused with congenital endothelial dystrophy type 2, CHED2 (217700) which is autosomal recessive, has an earlier presentation, and maps to a different region of chromosome 20.  Harboyan syndrome (217400) has similar corneal features but maps to a different location on chromosome 20 and is associated with sensorineural deafness.

The nosology of the corneal dystrophies is still evolving.  In the 2015 edition of the IC3D, this condition designated CHED1 is eliminated based on clinical and pathologic similarities to those in posterior polymorphous corneal dystrophy 1 (PPCD1, 122000).  However, while the loci for PPCD2 and CHED1 are located in the same pericentric region of chromosome 20, the purported mutations occur in different genes. 

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Penetrating keratoplasty carries a good visual prognosis, even when done late in life.

References
Article Title: 

IC3D classification of corneal dystrophies--edition 2

Weiss JS, Moller HU, Aldave AJ, Seitz B, Bredrup C, Kivela T, Munier FL, Rapuano CJ, Nischal KK, Kim EK, Sutphin J, Busin M, Labbe A, Kenyon KR, Kinoshita S, Lisch W. IC3D classification of corneal dystrophies--edition 2. Cornea. 2015 Feb;34(2):117-59. Erratum in: Cornea. 2015 Oct;34(10):e32.

PubMed ID: 
25564336
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