Keratoconus has been found in a large number of systemic conditions, such as connective tissue disorders, Down syndrome, and other 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.
Less than 10% of keratoconus cases have a positive family history and several mutations seem to be responsible. Mutations in the VSX1 homeobox gene (20p11.2) have been found in what is called KTCN1 keratoconus (the same gene is mutant in posterior polymorphous corneal dystrophy 1 ), inherited as an autosomal dominant trait.
Other forms of hereditary keratoconus caused by different mutations are: KTCN2 (608932) linked to a mutation on chromosome 16 (16q22.3-q23.1), KTCN3 (608586) by a mutation on chromosome 3 (3p14-q13), KTCN4 (609271) caused by a mutation on chromosome 2 (2p24), KTCN5 (614622) mapped to 5q14.1-q21.3, KTCN6 (614623) mapped to 9q34, KTCN7 (614629) mapped to 13q32, KTCN8 (614628) mapped to 14q24, and KTCN9 (617928) associated with a mutation in the TUBA3D gene located at 2q21.1.