Keratoconus 9

Background and History: 

Some diseases of the cornea (windshield of the eye) lead to an abnormal shape.  Since this tissue provides the majority of the focusing of images that enables us to see clearly, any change in its shape leads to blurring or distortion of vision.  Keratoconus is a heterogeneous disorder in which there is a bulging and conical shape to the cornea.  It is a progressive condition caused by numerous factors including a number of gene mutations.

Clinical Correlations: 

This usually bilateral condition begins in young people who notice the onset of blurred vision during the second or third decade of life.  Glasses may be unable to completely correct the blurriness because the cornea has an irregular conical shape (irregular astigmatism).  The abnormal shape may worsen slowly over several years but sometimes stabilizes for a period of time.  Eventually the distortion of the cornea resumes its progression.  Sometimes there is an acute worsening with the sudden onset of pain as the cornea becomes thinner and fluid seeps into it causing swelling (corneal hydrops) and a marked further decrease in vision.  This may heal over several months but frequently results in scarring with permanent loss of vision.  Most individuals have no other associated health problems.

Genetics: 

The vast majority (90%) of keratoconus occurs sporadically in individuals without a family history of the condition.  It can be a part of many systemic conditions and chromosomal disorders such as Down syndrome and individuals with a connective tissue disease.  It has also been associated with frequent eye-rubbing, allergies, or sometimes with long-term contact lens wear.  However, these associations may only be coincidental and the cause of keratoconus is unknown in most people.

Several genetic mutations have been found in scattered families in which multiple members had keratoconus.  Most such familial cases follow an autosomal dominant pattern of inheritance in which affected parents pass the trait directly to their offspring.

Keratoconus 9 described here has been associated with a specific DNA mutation found in a pair of identical twin sisters and two additional unrelated individuals.  The DNA change is present in only one of a pair of genes and therefore the corneal abnormality would be expected to be passed directly from parent to child.  However, the parents of the twins did not have the mutation and it is hypothesized that it arose de novo.  Further pedigrees will be needed to confirm this.

Diagnosis and Prognosis: 

The diagnosis of keratoconus is usually made by your eye doctor who has the special equipment to detect the cornea's abnormal shape.  Early in the course of this condition appropriately fitted contact lenses can sometimes restore normal or near normal vision.  With progression of the disease, this may no longer be effective and many patients eventually need corneal transplantation surgery which is usually successful.

There is no impact on longevity and most individuals lead otherwise healthy lives.

Additional Information
Inheritance/Pedigree: 
Autosomal dominant