Leber congenital amaurosis

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 15, 2016
StartDiseasesLeber congenital amaurosis

A congenital disorder is a condition that an individual is born with. Individuals who are born with Leber congenital amaurosis have severe vision problems throughout childhood and adulthood. A common cause of childhood blindness, Leber congenital amaurosis tends to be relatively stable or to progress slowly.

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Definition & Facts

Leber congenital amaurosis is a genetic disorder in which infants are born with impaired vision. Vision is impaired due to abnormalities of the retina which is the back layer of the eyeball that detects light and color.

In addition to impaired vision or blindness, Leber congenital amaurosis can also cause other vision issues like nystagmus. This condition can gradually worsen over time, but in some cases, it may remain stable throughout a patient's life. Leber congenital amaurosis affects about 2 to 3 out of every 200,000 people.

Symptoms & Complaints

Infants born with Leber congenital amaurosis have eyes that do not appear to be abnormal, aside from looking slightly sunken or deep-set. Though it is present at birth, it may take a while for Leber congenital amaurosis to be diagnosed because it can be hard to detect symptoms of bad eyesight in infants.

The lack of eyesight normally becomes noticed a few months after birth. Though people with Leber congenital amaurosis can see some bright lights and large shapes, most cannot see in much detail. Some people with Leber congenital amaurosis are legally blind, while others just have extremely bad eyesight.

In addition to vision loss, some individuals also suffer from nystagmus, which is a vision problem characterized by abnormal, involuntary eye movements. This type of eye movement disorder involves rapid movement of the eyes back and forth.

Leber congenital amaurosis can also cause an impaired transient pupillary light reflex, making patients very sensitive to bright lights. Children with Leber congenital amaurosis tend to press their eyes with their fists, knuckles, or fingers compulsively.

Individuals with Leber congenital amaurosis are more likely to develop cataracts later in life, and the condition is also associated with certain neurological disorders. Though it is unknown how they are related, people with Leber congenital amaurosis are more likely to have epilepsy, motor skill impairments, or developmental delays.

Causes

Leber congenital amaurosis is caused by a combination of different eye abnormalities. Individuals with Leber congenital amaurosis tend to have abnormally thin, cone-shaped corneas, constricted blood vessels in the cornea, abnormal photoreceptor cells in the retina, and degenerating supportive tissue around the retina.

All of these eye problems are caused by genetic mutations. These mutated genes may be inherited from parents, or they can occur spontaneously during fetal development. So far, researchers have identified at least 14 genes that may cause Leber congenital amaurosis if they are mutated. These genes are mostly genes that contain the coding information for proteins that build eye tissue, and when they do not work correctly, the eyes do not form correctly.

Most genes that cause Leber congenital amaurosis are inherited recessively which means that parents can be a genetic carrier for the condition without experiencing any symptoms themselves.

Diagnosis & Tests

Getting a diagnosis of Leber congenital amaurosis typically happens in mid infancy or early toddlerhood. The first step in diagnosis is a parent or doctor noticing that the infant does not respond to visual stimuli. This normally leads to an eye examination that looks for any obvious malformations, but infants with Leber congenital amaurosis usually have eyes that appear perfectly normal when examined with typical methods.

Since the condition also causes nystagmus, the doctor may assume that the infant just cannot see because of the abnormal eye movements. However, as they get older, it will become apparent that they cannot actually see even when their eyes are steady.

In order to actually diagnose Leber congenital amaurosis, a doctor will need to perform an electroretinography test. This test measures visual function and retinal activity. Infants with Leber congenital amaurosis will have almost no retinal activity at all. In rare cases where the Leber congenital amaurosis is very mild, a child may be able to function well enough that the condition is not discovered until they take a routine visual acuity test.

Treatment & Therapy

Most forms of treatment available to patients consist of assistive devices to maintain a normal lifestyle with the disease. Strong prescription glasses can provide some benefits if individuals have enough remaining vision. Canes, guide dogs, and other typical methods of functioning without vision all work well for people who have blindness due to Leber congenital amaurosis. Electronic aids can help individuals with vision issues to use technology and operate other devices.

Though there currently is not a widely available cure, there are some very promising clinical trials and studies that have been conducted. Gene therapy offers promise. In a clinical trial with patients who had a genetic mutation of the RPE65 gene, patients were given injections of healthy copies of the RPE65 gene. Though vision wasn't restored, there was increased sensitivity to light in the retina.

Prevention & Prophylaxis

Generally, two parents who have Leber congenital amaurosis will have a 25 percent chance of giving birth to a child who has the condition. Since a few associated genetic mutations that may cause the condition are dominant, chances can be even higher for some parents.

Families with a history of Leber congenital amaurosis can benefit from genetic counseling to assess the risk of giving birth to a child with Leber congenital amaurosis. However, there is no way of preventing the condition if a child is born with the precise genetic mutations that cause the condition. Some research with gene replacement therapy suggests that earlier treatment can reduce the risk of severe eye issues later in life.