SNP Shot: Genomic Insights

Leber congenital amaurosis (LCA) is a congenital (present at birth) eye disorder primarily affecting the retina, the light-sensitive tissue at the back of the eye. Individuals with LCA experience significant visual impairment, typically starting at birth or shortly thereafter. This impairment is often severe and can worsen over time.

Besides severe visual impairment, LCA is often linked to other vision issues such as heightened light sensitivity (photophobia), involuntary eye movements (nystagmus), and extreme farsightedness (hyperopia). The pupils' reaction to light is also affected; they may react slowly or not at all, failing to expand and contract normally.

A distinctive behavior associated with LCA is Franceschetti's oculo-digital sign, characterized by individuals poking, pressing, or rubbing their eyes with a knuckle or finger. This action often induces phosphenes, the sensation of seeing flashes of light. Researchers believe this behavior may contribute to the development of deep-set eyes in affected children.

In rare instances, individuals with LCA features may also exhibit delayed development and intellectual disability. The visual impairment can lead to social isolation in affected children. Early intervention strategies, including play, auditory stimulation, tactile experiences, comprehension activities, and other educational programs, can help prevent developmental delays in children with LCA.

There are at least 20 identified genetic subtypes of LCA, each distinguished by its specific genetic cause, the pattern of vision loss, and associated eye abnormalities.

Inheritance:

LCA typically follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of a mutated gene (one from each parent) to develop the condition. The parents, carrying only one copy of the mutated gene, usually show no signs or symptoms of LCA. However, when LCA is caused by mutations in the CRX or IMPDH1 genes, it follows an autosomal dominant inheritance pattern. In this case, only one copy of the altered gene is needed to cause the disorder. Most individuals with autosomal dominant LCA inherit the mutated gene from an affected parent. However, some cases arise from new gene variants in individuals with no family history of the condition.