Keratoconus 4

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. 


Less than 10% of keratoconus cases have a positive family history and several mutations seem to be responsible.  Mutations at the 2p24 locus on chromosome 2 seem to cause KTCN4 based on genome-wide linkage analysis in families from multiple out-bred populations.  The pattern of inheritance is autosomal dominant.

Other forms of hereditary keratoconus caused by different mutations are:  Mutations in VSX1 (20p11.2) cause KTCN1, KTCN2 (608932) is linked to a mutation on chromosome 16 (16q22.3-q23.1), and KTCN3 (608586) results from a mutation on chromosome 3 (3p14-q13).

Treatment Options: 

Contact lenses may correct vision satisfactorily in early stages of the disease but up to 20% of patients will eventually need a corneal transplant.

Article Title: 


Hutchings H, Ginisty H, Le Gallo M, Levy D, Sto?'sser F, Rouland JF, Arn?(c) JL, Lalaux MH, Calvas P, Roth MP, Hovnanian A, Malecaze F. Identification of a new locus for isolated familial keratoconus at 2p24. J Med Genet. 2005 Jan;42(1):88-94.

PubMedID: 15635082