OMIM ID:
Keratoconus 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The cornea progressively thins in the lower portion, usually in juveniles and young adults. The cornea may appear normal by slit lamp examination in early stages but keratoscopy can show steepening or distortion of the mires. Retinoscopy through dilated pupils often yields a ‘scissoring’ pattern. Early symptoms include uncorrectable blurring of vision and visual distortion. The central and lower cornea progressively thins with formation of a cone. A subepithelial iron line can sometimes be seen around the conical portion of the cornea (Fleischer ring). Vertical lines may be found in the deep portions of the stroma and in Descemet membrane (Vogt striae). The disease can progress for some years but there may also be periods of stability. Individuals with advanced disease may suffer acute painful episodes following breaks in the Descemet membrane with edema and opacification in the cone (hydrops), followed by stromal scarring.
Systemic Features
Keratoconus has been found in a large number of systemic conditions, such as connective tissue disorders, Down syndrome, and chromosomal disorders. It has been blamed on eye rubbing as is often seen in Leber congenital amaurosis and other ocular disorders as well as in atopic conditions and in individuals who have worn contact lenses for many years. Cause and effect in these situations is difficult to prove and it is likely that keratoconus is an etiologically heterogeneous disorder. Only keratoconus associated with single gene mutations are considered here.
Recent evidence suggests that corneal hydrops is strongly associated with mitral valve prolapse.
Genetics
Inheritance
Less than 10% of keratoconus cases have a positive family history and several mutations seem to be responsible. KTCN3 seems to be caused by a mutation located at 3p14-q13 as determined from linkage studies in a 2 generation Italian family. It is inherited in an autosomal dominant pattern.
Other forms of hereditary keratoconus caused by different mutations are: KTCN1 (148300) caused by mutations in the VSX1 gene at 20p11.2), KTCN2 (608932) from a mutation on chromosome 16 (16q22.3-q23.1), and KTCN4 (609271) caused by a mutation on chromosome 2 (2p24).
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission