Maumenee corneal dystrophy

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: 

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

Corneal Dystrophy, Congenital Endothelial 2

Clinical Characteristics
Ocular Features: 

Corneal clouding is usually evident at birth and in virtually all cases in the first decade of life.   Corneal edema is usually progressive and often leads to stromal scarring, neovascularization, and deposition of plaques eventually.  The ground glass appearance of the cornea at least initially is most pronounced peripherally.  When the ground glass appearance is present in young children, it may lead to the misdiagnosis of congenital glaucoma and some children have had glaucoma surgery.  However, no anatomic abnormalities of the anterior chamber angle have been observed and glaucoma does not seem to occur in this disorder as it does in CHED1.  Photophobia and tearing are uncommon. 

The corneal epithelium may become atrophic with partial loss of Bowman's membrane replaced by subepithelial fibrosis.  Corneal sensitivity is normal.  The stroma may have spheroidal degeneration resembling posterior polymorphous dystrophy.  Generalized edema may lead to marked thickening of the entire cornea.  The endothelium undergoes degeneration and cell loss is common, while those that remain often contain melanin granules.  Descemet's membrane is greatly thickened.  This condition may be stable in some individuals while others clearly have evidence of progression, and a few have some regression in childhood.  Vision may be quite good and few patients develop nystagmus.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is an autosomal recessive disorder resulting from mutations in the SLC4A11 gene located on chromosome 20 (20p13-12).  This disorder must be distinguished from Harboyan syndrome (#217400, CDPD1) from which it differs by the absence of neurosensory deafness.  The two disorders are allelic, however.  A clinically similar but less severe and genetically distinct form of congenital endothelial dystrophy, CHED1 (121700), can have a later age of presentation, maps to a different region of chromosome 20 ( 20p11.2-q11.2), and is inherited in an autosomal dominant pattern. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Corneal transplantation can be successful in restoring vision in 90% of cases, even when performed in adults.

References
Article Title: 

Congenital hereditary

McCartney A, Rice NS, Garner A, Steele AD. Congenital hereditary
corneal oedema of Maumenee: its clinical features, management, and pathology. Br J Ophthalmol. 1987 Feb;71(2):130-44.

PubMed ID: 
3548808
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