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Leber congenital amaurosis

Reviewed August 2010

What is Leber congenital amaurosis?

Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.

Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). 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. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.

A specific behavior called 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. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.

In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.

At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.

How common is Leber congenital amaurosis?

Leber congenital amaurosis occurs in 2 to 3 per 100,000 newborns. It is one of the most common causes of blindness in children.

What genes are related to Leber congenital amaurosis?

Leber congenital amaurosis can result from mutations in at least 14 genes, all of which are necessary for normal vision. These genes play a variety of roles in the development and function of the retina. For example, some of the genes associated with this disorder are necessary for the normal development of light-detecting cells 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 stick out from the surface of many types of cells. Cilia are necessary for the perception of several types of sensory input, including vision.

Mutations in any of the genes associated with Leber congenital amaurosis disrupt the development and function of the retina, resulting in early vision loss. Mutations in the CEP290, CRB1, GUCY2D, and RPE65 genes are the most common causes of the disorder, while mutations in the other genes generally account for a smaller percentage of cases. In about 30 percent of all people with Leber congenital amaurosis, the cause of the disorder is unknown.

Related Gene(s)

Changes in these genes are associated with Leber congenital amaurosis.

  • AIPL1
  • CEP290
  • CRB1
  • CRX
  • GUCY2D
  • IMPDH1
  • LCA5
  • LRAT
  • RD3
  • RDH12
  • RPE65
  • RPGRIP1
  • SPATA7
  • TULP1

How do people inherit Leber congenital amaurosis?

Leber congenital amaurosis usually has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

When Leber congenital amaurosis is caused by mutations in the CRX or IMPDH1 genes, the disorder has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In most of these cases, an affected person inherits a gene mutation from one affected parent. Other cases result from new mutations and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Leber congenital amaurosis?

These resources address the diagnosis or management of Leber congenital amaurosis and may include treatment providers.

  • Gene Review: Leber Congenital Amaurosis (http://www.ncbi.nlm.nih.gov/books/NBK1298/)
  • Genetic Testing Registry: Leber's amaurosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0339527)
  • Genetic Testing Registry: Leber congenital amaurosis 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/CN034165)
  • Genetic Testing Registry: Leber congenital amaurosis 10 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857821)
  • Genetic Testing Registry: Leber congenital amaurosis 12 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857743)
  • Genetic Testing Registry: Leber congenital amaurosis 13 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2675186)
  • Genetic Testing Registry: Leber congenital amaurosis 14 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2750063)
  • Genetic Testing Registry: Leber congenital amaurosis 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1859844)
  • Genetic Testing Registry: Leber congenital amaurosis 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858677)
  • Genetic Testing Registry: Leber congenital amaurosis 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858386)
  • Genetic Testing Registry: Leber congenital amaurosis 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858301)
  • Genetic Testing Registry: Leber congenital amaurosis 9 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837873)
  • National Eye Institute: Gene Therapy for Leber Congenital Amaurosis (http://www.nei.nih.gov/lca/)

You might also find information on the diagnosis or management of Leber congenital amaurosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/leber-congenital-amaurosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/leber-congenital-amaurosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Leber congenital amaurosis?

You may find the following resources about Leber congenital amaurosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Leber congenital amaurosis?

  • amaurosis, Leber congenital
  • congenital amaurosis of retinal origin
  • congenital retinal blindness
  • CRB
  • dysgenesis neuroepithelialis retinae
  • hereditary epithelial dysplasia of retina
  • hereditary retinal aplasia
  • heredoretinopathia congenitalis
  • LCA
  • Leber abiotrophy
  • Leber congenital tapetoretinal degeneration
  • Leber's amaurosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Leber congenital amaurosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Leber congenital amaurosis?

autosomal ; autosomal dominant ; autosomal recessive ; cell ; congenital ; cornea ; disability ; dysgenesis ; dysplasia ; epithelial ; gene ; inheritance ; involuntary ; keratoconus ; mutation ; nystagmus ; pattern of inheritance ; perception ; photophobia ; recessive ; retina ; sensitivity ; sign ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27. (http://www.ncbi.nlm.nih.gov/pubmed/18441371?dopt=Abstract)
  • Chung DC, Traboulsi EI. Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions. J AAPOS. 2009 Dec;13(6):587-92. doi: 10.1016/j.jaapos.2009.10.004. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20006823?dopt=Abstract)
  • Cremers FP, van den Hurk JA, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol Genet. 2002 May 15;11(10):1169-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12015276?dopt=Abstract)
  • den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008 Jul;27(4):391-419. doi: 10.1016/j.preteyeres.2008.05.003. Epub 2008 Jun 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18632300?dopt=Abstract)
  • Gene Review: Leber Congenital Amaurosis (http://www.ncbi.nlm.nih.gov/books/NBK1298/)
  • Hanein S, Perrault I, Gerber S, Tanguy G, Barbet F, Ducroq D, Calvas P, Dollfus H, Hamel C, Lopponen T, Munier F, Santos L, Shalev S, Zafeiriou D, Dufier JL, Munnich A, Rozet JM, Kaplan J. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. Hum Mutat. 2004 Apr;23(4):306-17. (http://www.ncbi.nlm.nih.gov/pubmed/15024725?dopt=Abstract)
  • Koenekoop RK, Cremers FP, den Hollander AI. Leber congenital amaurosis: ciliary proteins on the move. Ophthalmic Genet. 2007 Sep;28(3):111-2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17896308?dopt=Abstract)
  • Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv Ophthalmol. 2004 Jul-Aug;49(4):379-98. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15231395?dopt=Abstract)
  • Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, Mingozzi F, Bennicelli JL, Ying GS, Rossi S, Fulton A, Marshall KA, Banfi S, Chung DC, Morgan JI, Hauck B, Zelenaia O, Zhu X, Raffini L, Coppieters F, De Baere E, Shindler KS, Volpe NJ, Surace EM, Acerra C, Lyubarsky A, Redmond TM, Stone E, Sun J, McDonnell JW, Leroy BP, Simonelli F, Bennett J. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009 Nov 7;374(9701):1597-605. doi: 10.1016/S0140-6736(09)61836-5. Epub 2009 Oct 23. Erratum in: Lancet. 2010 Jan 2;375(9708):30. (http://www.ncbi.nlm.nih.gov/pubmed/19854499?dopt=Abstract)
  • Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27. (http://www.ncbi.nlm.nih.gov/pubmed/18441370?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2010
Published: July 7, 2014