Corneal dystrophy (ORPHA:34533)
A heterogeneous group of bilateral, genetically determined, non-inflammatory eye diseases that are usually restricted to the cornea. The designation is imprecise but remains in use because of its clinical value.
Epidemiology
Prevalence of the corneal dystrophies is variable but these conditions are rare. An indication of the precise number of each of the specific types of corneal dystrophies is unknown as all cases are not reported or recorded in a registry.
Clinical description
Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (superficial corneal dystrophy), the corneal stroma (stromal corneal dystrophy), or Descemet membrane and the corneal endothelium (posterior corneal dystrophy) (see these terms). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees.
Etiology
Different corneal dystrophies are caused by mutations in the CHST6, COL8A2, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TCF4, TGFBI, and UBIAD1 genes. Knowledge about the genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified.
Diagnostic methods
As clinical manifestations vary widely with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Clinical diagnosis is based on the age of onset and the clinical appearance of the cornea on slit-lamp biomicroscopy. When corneal tissue is excised, it should be examined by light microscopy and transmission electron microscopy (TEM) as this can establish the precise diagnosis of many corneal dystrophies. In dystrophies for which the genetic mutation has been identified, molecular genetic testing can confirm diagnosis.
Differential diagnosis
Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosinemia type 2, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans) (see these terms).
Antenatal diagnosis
A prenatal diagnosis of corneal dystrophies caused by known genetic mutations is theoretically possible but is not justified ethically for these non-life-threatening conditions.
Genetic counseling
Corneal dystrophies may have an autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Since the clinical characteristics and mode of inheritance of each of the well-defined corneal dystrophies are well established, genetic counseling can be offered to patients, particularly to provide genetic counseling on treatments and prognoses.
Management and treatment
The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment.
Prognosis
The prognosis varies from minimal effect on vision to corneal blindness, with marked phenotypic variability.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH