Leber Congenital Amaurosis Health Article

Definition

Leber congenital amaurosis (LCA) is a group of autosomal recessive-inherited eye disorders which lead to blindness at birth or within the first few years of life. Other manifestations of the disease may include hearing loss, mental retardation and decreased physical coordination.

Description

Vision is an important and complex sense by which the qualities of an object, such as color, shape, and size, are perceived through the detection of light. For proper vision, a critical series of biological steps must occur; if any of the steps in the process is abnormal, visual impairment or blindness may occur.

The process of vision begins with light that bounces off an object and passes through the outer coverings and lens of the eye and projects onto a layer of cells at the back of the eye called the retina. The retina contains two kinds of specialized cells types, called the rods and cones, that are responsible for sensing visual stimuli. When rods and cones are stimulated by light, impulses are conducted through the optic nerve to a region in the back of the brain known as the occipital lobe. The occipital lobe contains the visual cortex, the area of the brain that processes visual stimuli and integrates signals sent by the retina to obtain a composite image of an object.

Leber congenital amaurosis (LCA) is a term for a group of inherited conditions in which the rod and cone receptors in the retina are defective or missing. Without the proper function of these specialized cells, light cannot be sensed normally.

LCA is often referred to by other names, such as: congenital absence of the rods and cones, congenital retinal blindness, congenital retinitis pigmentosa, Leber congenital tapetoretinal degeneration, or Leber congenital tapetoretinal dysplasia. The disorder was first described by the German ophthalmologist, Theodor Leber, in 1869, who subsequently showed that it was an inherited defect. Although similarly named, LCA should not be confused with another disorder of sight, Leber optic atrophy, that was also discovered by Theodor Leber.

Genetic profile

Mutations in any one of at least six different gene groups may result in LCA. Each of the known genes produce proteins, which are located within the retinal rod and cone cells. These proteins participate in the detection of an incoming stimulus of light and the subsequent transmission of signals out of the retinal cells to the visual cortex of the brain. The different types of LCA and the corresponding genetic abnormality is described in the table below. These six identified mutations likely account for less than half of all diagnosed cases of LCA, and thus, there are additional mutations resulting in LCA that remain to be discovered.

LCA is a genetic condition and can be inherited or passed on in a family. The genetic defects for the disorder are all inherited as autosomal recessive traits, meaning that two mutant genes of the same group are needed to display the disease. A person who carries one mutant gene does not display the disease and is called a carrier. A carrier has a 50% chance of transmitting the gene to their children, who must inherit the same defective gene from each parent to display the disease. Since there are different genes that are responsible for causing LCA, two individuals with different types of LCA will have an unaffected child, as it is impossible for the child to inherit two of the same type of defective genes from the parents.

Demographics

LCA has been reported to account for at least 5% of all cases of inborn blindness, but several reports suggest that is an underestimation. In 1957, scientific investigators reported that one form of LCA was responsible for 10% of blindness in Sweden. Several years later, similar rates of LCA were found in people living in the Netherlands. While this suggests that the geographical distribution of LCA is not uniform and may be higher in certain ethnic groups, a comprehensive study has never been performed.