Leber Congenital Amaurosis

Overview

Leber congenital amaurosis (LCA) is a rare inherited disease of the retina, the light-sensing layer at the back of the eye. It is one of the most common causes of inherited blindness that begins in childhood. In LCA, the light-sensing cells (photoreceptors) of the retina do not develop or function properly, leading to severe vision loss that is present from birth or appears within the first months of life.

LCA is caused by changes (mutations) in any one of a number of genes that are important for the retina to work. Because it is usually inherited in an autosomal recessive pattern, a child typically develops the condition when they inherit a non-working copy of the gene from each parent. The severity and exact features vary depending on which gene is involved. Research has led to one of the first approved gene therapies for an inherited retinal disease, marking an important advance for certain forms of LCA.

Symptoms

Signs usually appear in infancy and may be noticed by parents or during early checkups. They include:

• Severely reduced vision or apparent blindness from birth or early infancy
• A roving or wandering gaze and difficulty fixing on objects
• Eyes that do not respond normally to light (poor pupil reactions)
• Involuntary eye movements (nystagmus)
• A habit of pressing or rubbing the eyes
• Sensitivity to light or, in some forms, poor vision in dim light
• Sometimes farsightedness

Because babies cannot describe their vision, signs such as not making eye contact, not following objects, or unusual eye movements should prompt an eye evaluation.

Causes

LCA is a genetic condition:

• Gene changes: Mutations in any of more than two dozen genes needed for the retina to develop and function can cause LCA.
• Inheritance: Most forms are inherited in an autosomal recessive pattern, meaning a child inherits a non-working gene copy from each parent, who are usually carriers without symptoms.
• Effect on the retina: The faulty genes disrupt how photoreceptor cells sense light or maintain themselves, leading to early, severe loss of vision.

The specific gene involved affects the features, severity, and whether certain treatments may be possible.

Risk Factors

• A family history of LCA or other inherited retinal disease
• Parents who are both carriers of the same gene change
• Parents who are blood relatives, which increases the chance of recessive conditions

Diagnosis

An eye specialist diagnoses LCA using examination and specialized testing:

• Eye examination: Assessing vision, eye movements, pupil responses, and the retina.
• Electroretinogram (ERG): A test that measures the electrical responses of the retina; in LCA these are severely reduced or absent.
• Retinal imaging: Photographs and scans such as OCT to assess the retina.
• Genetic testing: Identifies the specific gene involved, which helps confirm the diagnosis, guide counseling, and determine eligibility for gene-specific treatment.

Treatment

Treatment depends on the gene involved and focuses on support and, for some forms, targeted therapy.

• Gene therapy: A treatment is approved for LCA caused by changes in a specific gene (RPE65); it delivers a working copy of the gene to the retina and can improve some aspects of vision in eligible patients.
• Vision support and low-vision aids: Tools, training, and educational support to help children make the most of their remaining vision and develop skills.
• Treating related problems: Correcting farsightedness with glasses and managing other eye or associated conditions.
• Genetic counseling: Helps families understand inheritance and options.

Research into additional gene and cell-based therapies for other forms of LCA is ongoing.

Prevention and Family Planning

LCA cannot currently be prevented because it is inherited, but several steps can help families:

• Genetic counseling for families with a history of inherited retinal disease
• Genetic testing to identify carrier status and the specific gene
• Early eye evaluation for infants with vision concerns or a family history
• Early support services to aid a child's development and learning

When to See a Doctor

Have a baby or young child evaluated by an eye specialist if you notice:

• The child does not make eye contact or follow objects by the expected age
• Wandering eyes or involuntary eye movements
• Eyes that do not react normally to light
• Frequent eye rubbing or pressing

A family history of inherited retinal disease is also a reason to seek evaluation and genetic counseling. Early diagnosis allows for support services and assessment of treatment options.

Related Topics

Frequently Asked Questions

References

1. National Eye Institute (NEI). Inherited retinal diseases.
2. MedlinePlus Genetics, U.S. National Library of Medicine. Leber congenital amaurosis.
3. American Academy of Ophthalmology. Leber congenital amaurosis.
4. National Organization for Rare Disorders (NORD). Leber congenital amaurosis.