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Corneal Dystrophy, Macular

OMIM ID:

autosomal recessive

Corneal Dystrophy, Macular

Alternate Names

MCDC1
Groenouw type II corneal dystrophy
Fehr corneal dystrophy

Defective Genes

CHST6

Clinical Characteristics

Ocular Features

Macular corneal dystrophy is a progressive, bilateral disorder with increasing corneal cloudiness throughout life. The onset of corneal haze is variable.  It can be seen in infancy but usually becomes apparent in the second or later decades of life.  Visual impairment can be severe, especially by mid-life.  The stroma, Descemet membrane, and endothelium are involved as keratocytes and endothelial cells accumulate intracytoplasmic vacuoles of glycosaminoglycans.  Corneal thickness is reduced, presumably due to abnormally dense packing of collagen fibrils in the stroma.  The epithelium does not seem to be involved.

Based on immunohistochemical profiles of inclusions, as well as phenotypic differences, attempts have been made to distinguish at least three types of macular dystrophy, I, IA, and II.  This may not be justified as the same gene is involved, and especially since several types have been described within the same inbred family.  Most likely these are variations in the phenotypic expression of the same gene, a  feature of many genetic disorders.

Systemic Features

No extraocular abnormalities have been associated with this disorder.  However, variations in serum levels of antigenic keratin sulfate have been found.

Genetics

Inheritance

Homozygous mutations in the CHST6 gene (16q22) are responsible for this autosomal recessive corneal dystrophy.  More than 100 mutations have been found.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

Full thickness and deep anterior lamellar keratoplasty can improve vision and relieve symptoms but the disease can recur in the graft.  More than 40% of grafts have recurrent opacities after 10 years.  The recurrence risk is higher in patients with disease onset at age 18 years or younger and in those who had keratoplasty before the age of 30 years.

Selected Resources

Publications

Displaying 1 - 4 of 4

Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty for Macular Corneal Dystrophy and Risk Factors of Recurrence

PubMedID: 23017278

Linkage of a gene for macular corneal dystrophy to chromosome 16

PubMedID: 8644739

Macular Corneal Dystrophy in Iceland

PubMedID: 8684802

Macular corneal dystrophy: A review

PubMedID: 29604391