The revolution of the genetic diagnosis of inherited visual disorders
Leber congenital amaurosis belongs to a group of retinal dystrophies. It's a rare genetic disease of the retina characterised by degeneration and gradual loss of the photoreceptors in the retina (rods and cones) from the first few months of birth.
Its rate of incidence is 1 in 35,000 newborns and makes up around 10 to 18% of cases of congenital blindness.
Clinically, it is characterised by a serious visual deficit in the first few years of life. Other symptoms may include strabismus (a deviation of one of the eyes), nistagmus (quick involuntary movements of the eye as its impossible to stare) and photophobia (anormal sensitivity to light). Frequently, children affected by this disease close their eyes and fists at the same time (it is called Franceschetti's oculo-digital sign). In addition, some children may suffer from a loss of hearing, neurological changes or psychomotor retardation.
It is a genetic disease caused by a mutation of some genes that encode specific retinal proteins. Multiple genes that might be responsible for the appearance of this disease have been identified. Therefore, it's a hereditary disease and follows a recessive autosomal pattern in the majority of cases. This means that both parents must be carriers of the anomalous genes even thought they do not manifest the disease. It presents itself when the child inherits a copy of the mutated gene from each of the parents.
Treatment is mainly support and includes using visual aids like special filters that improve sensitivity to contrast, different types of telescopes for farsight and magnifying classes for shortsight.
In 2018, the use of the drug voretigene neparvovec (the commercial name is Luxturna) was approved for the treatment of some cases of Leber congenital amaurosis.
Luxturna can only be used while patients have enough working or viable retina cells and when the disease is caused by mutations of a specific gene, the RPE65 gene, which is responsible for the production of an enzyme necessary for the normal functioning of the retina cells.
It is a gene therapy and involves injecting a modified virus that transports normal copies of the missing RPE65 gene to the cells of the retina. This contributes an improvement in the functioning of these cells and slows the onset of the disease. The treatment must be administered in the form of an injection in the back of the eye, below the retina, by an experienced vitreo-retinal surgeon.
Frequently asked questions
A genetic study using a blood test can help to determine which gene has mutated in each individual case. If treatment of the RPE65 gene and maintaining sufficient viable retina cells is concerned, the application of Luxturna gene therapy can be assessed.
Genetic studies allow us to find out which mutations are responsible for a patient's particular hereditary disease. A person's full genetic information is stored in the DNA of their cells. To detect these mutations, it's necessary to use sophisticated DNA analysis techniques. Normally, it is enough to draw a sample of blood from the patient, like when we take a conventional blood sample.
The genetic study will be used both to confirm the clnical diagnosis and to inform the rest of the family about whether they are healthy, carriers or affected by the disease. In addition, those relatives that have a genetic mutation could also find out if they are at risk of passing the disease to their offspring.