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Leber congenital amaurosis
URL of this page: https://medlineplus.gov/genetics/condition/leber-congenital-amaurosis/

Leber congenital amaurosis

Description

Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) are part of a spectrum of inherited diseases that are characterized by severe visual impairment that occurs early in life. Leber congenital amaurosis typically refers to vision loss that occurs during the first year of life, while EOSRD typically refers to vision loss that occurs between the ages of 1 and 5 years. The word "amaurosis" comes from the Greek word for darkness and represents the severe vision loss that is associated with this condition. The visual impairment in people with Leber congenital amaurosis may worsen over time, depending on the specific underlying cause. 

There are many types of Leber congenital amaurosis. This group of disorders primarily affects the specialized tissue at the back of the eye that detects light and color (retina).  Although cases of Leber congenital amaurosis are rare, this group of disorders is among the leading genetic causes of severe vision loss in infants and is one of the most severe forms of inherited retinal disease. 

Children with Leber congenital amaurosis often have additional vision problems, which can include an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). In many affected individuals, the pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Some children may also develop strabismus, which is a condition in which the eyes do not point in the same direction (misalignment). A form of strabismus in which one or both eyes turn inward (esotropia) is the most common type seen in children with Leber congenital amaurosis.

A specific behavior called Franceschetti's oculo-digital sign is a characteristic feature of Leber congenital amaurosis. This sign consists of individuals poking, pressing, and rubbing their eyes with a knuckle or finger. Poking the eyes often results in the sensation of flashes of light called phosphenes. Researchers suspect that this behavior may contribute to the appearance of deep-set eyes in affected children. Repeated eye rubbing or pressing may also increase the risk of developing keratoconus, a condition in which the clear front surface of the eye (cornea) becomes thinner and bulges outward. This can lead to blurred or distorted vision. As a result, frequent eye rubbing may be discouraged.

Children with Leber congenital amaurosis may benefit from early intervention programs and educational opportunities that are designed for children with visual impairment. These programs may help prevent the learning delays that can accompany vision loss.

When Leber congenital amaurosis occurs without additional signs and symptoms, it is called nonsyndromic Leber congenital amaurosis. Because signs and symptoms that are similar to those seen in people with Leber congenital amaurosis can also occur as part of a syndrome that affects other organs and tissues in the body, performing a careful clinical evaluation is an important part of the diagnostic process. 

Frequency

Leber congenital amaurosis occurs in two to three in 100,000 newborns.

Causes

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in one of over 20 different genes can cause Leber congenital amaurosis. These genes are all necessary for normal vision and play a variety of roles in the development and function of the retina. For example, some of the genes that are associated with this disorder are essential for the normal development of light-sensing cells in the retina called photoreceptors. Other genes are involved in phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. Still other genes play a role in the function of cilia, which are microscopic, finger-like projections that are found in many types of cells, including the retina's photoreceptors. These cilia are required for proper photoreceptor function.

Pathogenic variants in the genes that are associated with Leber congenital amaurosis disrupt the development or function of the retina, resulting in early vision loss. Pathogenic variants in the CEP290, CRB1, GUCY2D, and RPE65 genes are among the most common causes of Leber congenital amaurosis. The CEP290 gene plays a role in the function of cilia, while the CRB1 gene helps with the development of photoreceptor cells. The GUCY2D gene is important for phototransduction. The RPE65 gene plays an important role in the visual cycle, which is the process that helps recycle light-sensitive molecules that are needed for vision.

Despite advances in genetic testing, a pathogenic variant may not be found in 20 to 30 percent of all people with Leber congenital amaurosis. In these cases, the cause of the disorder is unknown.

When Leber congenital amaurosis occurs as part of a genetic syndrome, it is caused by pathogenic variants in the gene that is associated with that syndrome.

Learn more about the genes associated with Leber congenital amaurosis

Additional Information from NCBI Gene:

Inheritance

Leber congenital amaurosis can be inherited in different ways, depending on the particular gene involved.

The condition is typically inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a pathogenic variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

In some cases, Leber congenital amaurosis is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, a person with Leber congenital amaurosis inherits the pathogenic variant from a parent. Other cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

When Leber congenital amaurosis occurs as part of a syndrome, it follows the inheritance pattern of that syndrome. 

Other Names for This Condition

  • Amaurosis congenita of Leber
  • Congenital retinal blindness
  • LCA
  • Leber's amaurosis
  • Leber's disease

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

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