Leber Congenital Amaurosis

National Organization for Rare Disorders, Inc.

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  • LCA

Disorder Subdivisions

  • None

General Discussion

Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or a cone shape to the front of the eye (keratoconus). LCA is usually inherited as an autosomal recessive genetic condition.


Children with LCA are born with an absence of functioning light-gathering cells (rods and cones) of the retina. Absence or reduction of the electrical activity of the retina is always observed and is necessary for the diagnosis of LCA.

A decrease in visual responsiveness at birth is the first sign of the disease. Often the child will poke, press and rub the eyes to stimulate the retina to produce light (Franceschetti's oculo-digital sign). This activity may cause the eyes to become sunken or deep set (enophthalmos).

Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or abnormal protrusion of the front (anterior), clear portion of the eye through which light passes (cornea) (keratoconus). In addition, some infants may exhibit hearing loss, mental retardation, and/or developmental delay.

Specific types of LCA have been defined based on the causative gene. Some types are associated with little change in vision over time (stationary) while others become more severe over time (progressive).


Mutations in twelve genes are thought to be responsible for 40-50% of all LCA. LCA is usually inherited as an autosomal recessive genetic condition. Mutations in 11 genes are associated with this type of LCA: GUCY2D, RPE65, SPATA7, AIPL1, LCA5, RPGRIP1, CRB1, CEP290, IMPDH1, RD3 and RDH12.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Rarely, LCA is inherited as an autosomal dominant genetic disorder. Mutations in the CRX gene are associated with this type of LCA.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

Affected Populations

The prevalence of LCA has been estimated to be 2-3/100,000 births. This disorder affects males and females in equal numbers.

Standard Therapies


Electroretinography (ERG) is used to assess visual function by measuring activity in the retina. Infants with LCA have absent or reduced electrical activity of the retina. Molecular genetic testing is available for the 12 genes associated with LCA. Clinical signs and symptoms can be helpful in determining which genes to test for, and in what order.


Treatment for LCA is symptomatic and supportive. Genetic counseling is recommended for families of affected children.

Investigational Therapies

Clinical trials of gene replacement therapy for LCA caused by RPE65 mutations have shown potential improvement in vision without harmful effects.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


Contacts for additional information about Leber congenital amaurosis:

Peter Francis, MD, PhD

Associate Professor

Director Translational Clinical Trials Center

Casey Eye Institute/OHSU

3375 SW Terwilliger Blvd.

Portland, Oregon 97239

Tel: 503-418-1627

Fax: 503-494-7233

Richard Alan Lewis M.D., M.S.

Professor, Departments of Ophthalmology, Medicine,

Pediatrics, and Molecular and Human Genetics


Faculty Associate, Huffington Center on Aging

Cullen Eye Institute NC-206

Baylor College of Medicine

One Baylor Plaza

Houston, Texas 77030

Voice: 713-798-3030

Fax: 713-798-3042

Email: rlewis@bcm.tmc.edu



Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008; 358: 2231, 9.

Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008; 19: 979, 90.

Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008; 358: 2240, 8.

Simonelli F, Ziviello C, Testa F, et al. Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4284-90.

Apushkin MA, Fishman GA. Attainment of educational levels in patients with Leber's congenital amaurosis. Ophthalmology. 2006 Mar;113(3):481-2.

Perrault I, Hanein S, Gerber S, et al. Retinal dehydrogenase 12 (RDH12) mutations in leber congenital amaurosis. Am J Hum Genet. 2004; 75: 639, 46.

Cremers FP, van den Hurk JA, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol Genet. 2002; 11: 1169, 76.

Huber A. Genetic diseases of vision. Curr Opin Neurol. 1994;7:65-68.

Kanski JJ, ed. Clinical Ophthalmology, 2nd ed. Butterworth-Heinemann. 1990:375.


Weleber RG, Francis PJ and Trzupek KM. Leber Congenital Amaurosis. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Last Updated: 3/30/10. Available at http://www.genetests.org. Accessed 5/10


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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.