Rare Ophthalmology News

Disease Profile

Leber congenital amaurosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

H35.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

LCA; Congenital absence of the rods and cones; Congenital retinal blindness;

Categories

Congenital and Genetic Diseases; Eye diseases

Summary

Leber congenital amaurosis (LCA) is an eye disorder that primarily affects the retina. People with this condition typically have severe visual impairment beginning in infancy. Other features include photophobia, involuntary movements of the eyes (nystagmus), and extreme farsightedness. The pupils also do not react normally to light. Additionally, the cornea may be cone-shaped and abnormally thin (keratoconus). Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger.[1] Different subtypes have been described. The different subtypes are caused by mutations in different genes. Some of these subtypes are also distinguished by their patterns of vision loss and related eye abnormalities. Treatment includes correction farsightedness and use of low-vision aids when possible.[2]

Symptoms

Leber congenital amaurosis (LCA) primarily affects the retina, the specialized tissue at the back of the eye that detects light and color. Beginning in infancy, people with LCA typically have severe visual impairment. This is most often non-progressive, but sometimes it very slowly worsens over time. Other vision problems associated with LCA include:[2][3]

  • Photophobia
  • Nystagmus
  • Clouding of the lens of the eyes (cataract)
  • Crossed eyes (strabismus)
  • Enophthalmos (eye balls are dislocated backward)
  • Abnormal retinal pigment
  • Extreme farsightedness (hyperopia)
  • Pupils that may not react normally to light; they may expand and contract more slowly than normal, or they may not respond to light at all
  • Keratoconus, a condition in which the cornea is cone-shaped and abnormally thin, may also be present

A specific behavior called Franceschetti's oculodigital sign is characteristic of LCA. This behavior consists of poking, pressing, and rubbing the eyes with a knuckle or finger. It may possibly contribute to deep-set eyes and keratoconus in affected children.

In rare cases, delayed development, hearing loss, and intellectual disability have been reported in people with the features of LCA. However, it is unclear whether these people actually have LCA or another syndrome with similar signs and symptoms.[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of retinal pigmentation
0007703
Abnormality of the optic disc
0012795
Severely reduced visual acuity
Marked vision impairment
Severe visual impairment
Severely impaired vision

[ more ]

0001141
30%-79% of people have these symptoms
Abnormal electroretinogram
0000512
Abnormality of neuronal migration
0002269
Aplasia/Hypoplasia of the cerebellar vermis
0006817
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Encephalocele
0002084
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Keratoconus
Bulging cornea
0000563
Muscular hypotonia
Low or weak muscle tone
0001252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Seizure
0001250
5%-29% of people have these symptoms
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Voretigene neparvovec-rzyl(Brand name: Luxturna) Manufactured by Spark Therapeutics, Inc
      FDA-approved indication: An adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Patients must have viable retinal cells determined by a treating physician.
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • The Foundation for Fighting Blindness provides information on their Web site on leber congenital amaurosis. Click on the link to view this information.
        • Genetics Home Reference (GHR) contains information on Leber congenital amaurosis. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • The American Society of Gene & Cell Therapy provides information on the treatment of genetic eye diseases.
          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Leber congenital amaurosis in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            Orphanet
            Orphanet
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Leber congenital amaurosis. Click on the link to view a sample search on this topic.

            References

            1. Leber congenital amaurosis. Genetics Home Reference. August 2010; https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis.
            2. Weleber RG, Francis PJ & Trzupek KM. Leber Congenital Amaurosis. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK1298/.
            3. Amaurosis Retiniana Congénita de Leber. FEDER. https://enfermedades-raras.org/index.php/component/content/article?id=717.
            4. Leber congenital amaurosis. Genetics Home Reference. August 2010; https://ghr.nlm.nih.gov/condition/leber-congenital-amaurosis. Accessed 7/26/2012.

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