This page provides information about Leber congenital amaurosis, its symptoms, causes and what treatment options are available.
What is Leber congenital amaurosis?
Leber congenital amaurosis (LCA) is the most common genetic cause of childhood blindness and affects about 15,000 people in the Western world. For most people with LCA, there is currently no approved treatment available. ProQR is aiming to change that.
The symptoms usually appear in infancy or in childhood and are characterized by severe loss of vision. Other symptoms can include eye shaking (nystagmus), eye-poking (Franceschetti's oculo-digital sign), night blindness (nyctalopia) and sensitivity to light (photophobia). The severity of vision loss and presence of other symptoms depend on what gene is involved.
An inherited retinal disease (IRD)
LCA is a genetic disease that is almost always passed down through the autosomal recessive pattern of inheritance. This means that LCA patients have mutations in both gene copies. In this type of inheritance, the parents are carriers, unaffected by LCA. Each parent has only one mutated LCA gene copy and one normal copy. Each of their children has a 25 percent risk of inheriting the two LCA gene copies (one from each parent) which then cause LCA.
Autosomal recessive inheritance
What causes LCA?
LCA is a genetic disease that causes a mistake, or mutation, in the patient’s DNA. Because of the mutation, an essential protein in the eye cannot function or is missing, and this leads to the deterioration of the light detecting cells in the retina.
There are over 19 known genes in which mutations can cause LCA. The most common mutation causing LCA is the p.Cys998X mutation, also known as c.2991+1655A>G, in the CEP290 gene. This mutation causes Leber congenital amaurosis type 10 (LCA10).
LCA is a rare IRD affecting 2 to 3 people per 100,000 newborn children and arises due to a mutation in one of a wide variety of genes; CEP290, RPE65, GUCY2D, RPGRIP1, RDH12, SPATA7, AIPL1, RD3, CRB1, CRX, IMPDH1, IQCB1, KCNJ13, LCA5, NMNAT1, and TULP11.
Some of these genes are necessary for the normal development of the rod and cone photoreceptor cells, phototransduction and cilia formation. Cilia are important structures in photoreceptors and inner ear cells involved in vision and hearing.
To know what mutation is causing LCA, genetic testing is necessary. Genetic testing is the only way to receive an accurate diagnosis and will help find out if there are treatments or clinical trials available.Genetic testing
What are the symptoms of LCA?
LCA is commonly detected in children who display profound visual impairment, don’t show clear focus on anything within their environment and it is characteristic for children to poke and press their eyes (Franceschetti's oculo-digital sign). This can cause damage to the cornea (keratoconus) and lens and may result in a loss of fatty tissue around the eyes causing the eyes to look deep-set.
Involuntary eye movements or eye shaking (nystagmus), increased light-sensitivity (photophobia), night blindness (nyctalopia) and far sightedness (hyperopia) are other symptoms associated with LCA. The extent and time course of retinal degeneration depends on the type of LCA the child has and for some types of LCA, the vision (or lack of vision) remains stable.
Is there a cure for LCA?
For people with RPE65 mediated LCA2, a gene therapy was approved in 2017 by the US FDA and in 2018 by EMA. But, for the majority of LCA patients, there is currently no treatment available. At ProQR we are working hard to change that. We are developing sepofarsen, an investigational RNA therapy for the most common mutation causing LCA.
Learn more about sepofarsen for CEP290 mediated LCA10.
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