Leber congenital amaurosis

Jackson was diagnosed with Leber congenital amaurosis, a retinal degenerative condition, in 2008 aged two and half months. 

Find out how the Leber congenital amaurosis research we fund will have a huge impact for people like Jackson who are living with the condition.

What is Leber congenital amaurosis?

Leber congenital amaurosis (LCA) is used for a group of genetic eye conditions that cause blindness or severe vision loss. It is typically congenital or noted within the first six months of life.

Even though it is rare, LCA is one of the most common causes of severe sight loss in children. It affects around two or three of every 100,000 babies born each year.

LCA mainly impacts the retina, the specialised light-sensitive layer that lines the back of the eye. It affects the light-sensing cells called photoreceptors, which play a vital role in making eyesight possible by converting light into electrical signals that are transmitted to the brain. When these cells stop working properly or are lost, this causes sight loss.

There are several different types of LCA, which are distinguished by their genetic cause, patterns of sight loss and related eye abnormalities.

Typically, symptoms will be present from birth or the first months of life, and where there is residual vision, it may get worse over time. However, the severity of the symptoms and speed of sight loss can vary widely between patients.

What causes Leber congenital amaurosis?

Scientists have so far identified faults in at least 27 different genes that can cause Leber congenital amaurosis. Faults in these genes account for about 80 to 90 percent of cases of LCA – and so it is likely that more are yet to be identified. The most commonly affected genes are CEP290, CRB1, GUCY2D, RDH12and RPE65.

Each of the genes associated with LCA provides the instructions for making various proteins that play important roles in the healthy development and functioning of the retina. For instance, some are essential for the correct development of photoreceptor cells, while others are involved in converting light into electrical signals. Faults in these genes disrupt the smooth working of the retina, resulting in sight loss.

Is Leber congenital amaurosis genetic or congenital?

LCA is a congenital condition because it is present from birth. It is also a genetic condition caused by faulty genes passed down to an affected child from their parents.

LCA is almost always inherited in an autosomal recessive inheritance pattern. Both parents will have one faulty copy of an LCA gene and one healthy copy.

They will typically be unaware they carry the faulty gene, however, as they do not have sight loss. Each of their children will have a one in four chance of inheriting the two faulty copies of the gene (one from each of their parents) needed to develop the condition.

In rare cases, LCA can have an autosomal dominant pattern of inheritance – meaning that only one copy of the faulty gene is enough to cause the condition. The child will usually inherit the faulty gene from one affected parent.

What are the signs and symptoms of Leber congenital amaurosis?

A child with Leber congenital amaurosis will usually have severe visual impairment from birth. Within the first few months of life, parents will often notice their baby isn’t responding to normal visual cues – such as following moving objects.

The child may also have involuntary eye movements, known as nystagmus – and might habitually poke, press and rub their eyes with a knuckle or finger, which may contribute to their eyes looking sunken or deep-set. They may dislike bright light or, rarely, are very attracted to light.

Other symptoms of LCA include:

• Keratoconus – an abnormal shape to the cornea at the front of the eye,
• Light sensitivity – photophobia,
• Cataracts – clouding of the lens of the eyes,
• Strabismus – crossed eyes,
• Enophthalmos – the eyeballs are sunk backward,
• Farsightedness – The eyes are smaller than normal, meaning it is harder to bring an image into focus.
• Slow or missing pupil reactions – the pupils don’t adjust normally to changes in light conditions.

In rare cases, a child may have symptoms affecting other parts of the body, including kidney disease, hearing loss, learning difficulties and/or developmental delay. However, this may indicate that they have a related syndrome rather than LCA.

How is Leber congenital amaurosis diagnosed? 

A test known as electroretinography (ERG) can help doctors to assess how well a child’s retina is working.

A child with LCA will have abnormally low or no electrical activity due to problems with their photoreceptors. As the retina breaks down and starts to get thinner over time, this can also lead to abnormal changes to the pigment at the back of the eye, which the eye doctor can see from clinical examination or specialised photographs.

Genetic testing can help confirm an LCA diagnosis and identify the responsible faulty gene. This can also provide information about the inheritance pattern of the condition and risks to other family members, helping to inform accurate genetic counselling.

How is Leber congenital amaurosis treated? 

Unfortunately, there is currently no cure for Leber congenital amaurosis. However, the development of cutting-edge gene therapies is offering hope for some patients. It is important to note that these new treatments are gene-specific, meaning they are only suitable for a small group of patients. They work by introducing a healthy copy of the faulty gene into the eye.

In 2017, the US Food and Drug Administration (FDA) approved the first gene therapy for Leber congenital amaurosis. The treatment, called ‘voretigene neparvovec’ (brand name Luxturna), is currently approved to treat patients with LCA caused by faults in the RPE65 gene. It aims to deliver healthy copies of the RPE65 gene into the eye, restoring the levels of an enzyme needed for the healthy functioning of photoreceptors.

In November 2018, the European Medicines Agency (EMA) approved Luxturna, making it the first and only gene therapy available in Europe to treat inherited retinal disease. In the UK, affected patients can receive this treatment under the NHS at four specialist centres – in London, Manchester and Oxford.

Luxturna is administered by an injection underneath the patient’s retina that is received under general anaesthetic. While the treatment does not completely restore vision, it can help prevent further sight loss and restore some functional vision in LCA patients.

However there is a risk of surgical complications, which may lead to further sight loss.

Latest Research on Leber congenital amaurosis

There is much ongoing research into finding the remaining genes that cause LCA and developing new treatments that can help slow down, stop or reverse sight loss in patients.

Scientists are investigating several gene therapies that could benefit people with faults in genes that cause LCA. For example, Fight for Sight helped to fund the initial research that led to the world’s first clinical trial of a potential new genetic technique for patients with LCA caused by faults in the CEP290 gene.

Other approaches include developing new small-molecule drugs – and stem cell-based therapies, which involve transplanting new retinal cells into the eye to replace those that are damaged.

Think you have Leber congenital amaurosis? Here's what to do.

Some people with LCA may benefit from low-vision aids to help maximise their remaining sight, such as electronic, computer-based and optical aids.

If someone in your family is affected with LCA, you can access genetic testing along with support from a genetic counsellor. As well as helping you to make informed medical and personal decisions, a genetic diagnosis will also provide up-to-date information about potentially suitable new treatments that are currently in development.

Have your eyes tested every two years even if you think your vision is fine. An eye test can spot some eye conditions and, if caught early, treatment may prevent further deterioration.

Last updated December 2023
Approved by

.