Leber congenital amaurosis is named after Theobald Leber a German ophthalmologist who first described the condition in the 19th century. Apart from vision loss other phenotypes are also characteristic of LCA including nystagmus (roving eye or involuntary eye movements), cataract, and in some cases aversion to light.
There are quite a number of genetic mutations that can lead to several forms of LCA which result in varying degrees of severity.
Following are some of the genes whose mutations can lead to LCA: -
CRX - codes for cone-rod homeobox protein that's involved in the synthesis of other important retinal genes. Mutations in this gene cause degeneration of photoreceptors.
REP65 - codes for a protein called retinal pigment epithelium-specific protein. Mutations interfere with the recycling of retinol which is a chemical needed for the eye to capture light. The gene has been the target of several successful gene therapy trials - see below.
RDH12 - codes for a protein called retinol dehydrogenase 12. It's found in retinol photoreceptor cells and mutations lead to a severe form of LCA.
CRB1 - codes for a protein called crumbs homolog 1. The gene is similar to the crumbs gene found in the drosophila fruit fly. In fact the gene was first seen to cause retinal degeneration in the fruit fly.
GUCY2D - codes for a protein called guanylate cyclase 2D. It is an enzyme that makes an important messenger called cyclic GMP. Mutations of the gene lead to abnormal concentrations of the messenger which causes degeneration of photoreceptor cells.
Leber congenital amaurosis is inherited in an autosomal recessive manner. This means that both parents must have the mutated gene and pass it on for a child to be born with the disorder. The parents are unaffected carriers and the chance of each of their children inheriting the condition is 25% or 1 in 4. This doesn't mean that if two carrier parents have four children at least one will have the condition. Any number of them could have LCA or none at all. The same odds are present with each birth.
LCA is proving to be extremely receptive to gene therapy treatment where faulty genes are replaced by functioning ones. There have been several successful clinical trials in the United States and the United Kingdom where patients have had much of their vision restored.
The long term aim is that gene therapy treatments will be widely available so that as soon as someone is diagnosed with LCA or other vision loss disorders they can be implemented.