SLC4A11

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

Harboyan Syndrome

Clinical Characteristics
Ocular Features: 

The combination of congenital endothelial dystrophy and progressive neural deafness is known as Harboyan syndrome.  This disorder must be distinguished from another autosomal recessive disorder, congenital endothelial dystrophy 2 or CHED2 (217700), in which deafness does not occur.  While the corneal disease in Harboyan is present at birth, the deafness often does not become obvious until the second and third decades of life although audiometry can detect some hearing loss in the first decade.  The cornea is thickened and edematous resulting in various degrees of visual impairment, even to the level of counting fingers.  Electrophysiologic studies have been normal.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is an autosomal recessive disorder caused by a mutation in the SLC4A11 gene located on chromosome 20 (20p13-12).  It is allelic to simple, congenital endothelial corneal dystrophy (CHED2) (217700).  About half of reported cases occur sporadically and the rest have been reported in offspring of consanguineous matings.  Less than 30 cases have been reported worldwide.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Corneal transplantation is the treatment of choice and can result in substantial visual improvement.

References
Article Title: 

Congenital hereditary endothelial dystrophy with

Desir J, Abramowicz M. Congenital hereditary endothelial dystrophy with
progressive sensorineural deafness (Harboyan syndrome). Orphanet J Rare Dis. 2008 Oct 15;3:28. Review.

PubMed ID: 
18922146

Congenital corneal dystrophy

Harboyan G, Mamo J, Kaloustian V der, Karam F. Congenital corneal dystrophy.
Progressive sensorineural deafness in a family. Arch Ophthalmol. 1971 Jan; 85(1):27-32.

PubMed ID: 
5312820
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