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Leber Congenital Amaurosis

Amaurosis Congenita of Leber

Leber congenital amaurosis is a rare autosomal recessive genetic disease of the retina characterized by an early onset of nystagmus, subnormal pupillary function, and blindness. A complete ophthalmologic exam, electroretinography, as well as genetic studies, are necessary steps in order to make the diagnosis.


Leber congenital amaurosis (LCA) is considered to be one of the most common (but also one of the most severe) hereditary disorders of impaired vision that develop during the first several years of life [1]. LCA is principally transferred through an autosomal recessive mode of inheritance, and first clinical signs appear after only 6 months in most patients [2] [3] [4] [5]. Phenotypic features are broad in this inherited retinal dystrophy, as numerous mutations cause variably progressive degeneration of the retina and loss of its function [2] [3] [6]. In virtually all cases, however, the clinical presentation is comprised of vision loss and diminished pupillary responses [2]. The inability of eye fixation is readily observed during the first few months of life, whereas refractive errors (hypermetropia, myopia), as well as photophobia, constant eye poking, pressing, or rubbing (known as Franceschetti signs) and consequent enophthalmos are commonly encountered [2] [7]. Other notable features include nystagmus, keratoconus, night blindness (in later life), and the development of juvenile cataracts [2] [7]. In many patients, unfortunately, visual acuity is severely reduced, and the perception of light is markedly impaired [2]. Thus, with a somewhat different clinical course, permanent and irreversible blindness ensues, but rare patients have known to improve overall visual function [2] [3] [6] [7].

Pediatric Disorder
  • Disorders, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA. 7 College of Veterinary Medicine and Mason Eye Institute, University of Missouri-Columbia, Columbia, MO 65212, USA. 8 Departments of Ophthalmology and Visual Sciences and Pathology[doi.org]
Central Scotoma
  • Visual field testing shows an enlarging central scotoma. Fluorescein angiography may be useful in the acute phase.[patient.info]
Unilateral Ptosis
  • Two siblings are described with clinical features of Joubert syndrome associated with unilateral ptosis, severe visual disturbances with normal appearing fundi, and an occipital meningocele; one child also had polydactyly.[ncbi.nlm.nih.gov]
Narrow Forehead
  • We report on two sisters who were born to a consanguineous couple and had retinitis pigmentosa-like pigmented retinal lesions, alternating exotropia, bilateral cataracts, and anomalous coarse facies characterized by deformed skull with narrow forehead[ncbi.nlm.nih.gov]


Although several forms of inherited retinal disorders may be included in the differential diagnosis, initial recognition of LCA in early life can be made with a comprehensive clinical assessment. Firstly, a detailed patient history addressing the course and progression of symptoms should be obtained from the parents, after which a complete physical examination needs to be carried out. If the ocular exam is conducted properly, typical signs and symptoms of LCA can be observed and a presumptive diagnosis of a retinal dystrophy might be made [2]. In fact, the physical examination is considered to be the pivotal part of the diagnostic workup, as both physical and ophthalmoscopy findings (a myriad of fundus abnormalities is seen, such as the salt-and-pepper appearance of the retina) are highly indicative of LCA [2] [6]. A more concrete diagnosis is made through the use of an electroretinogram (ERG), which shows reduced or completely absent activity of the retina, pointing toward retinal dysfunction as the cause of symptoms [1] [2] [4] [6]. In addition, optical coherence tomography (OCT) is also recommended by some authors, as it allows measuring of the retinal thickness that is often reduced in LCA patients [1] [4] [6]. To exclude other retinal dystrophies and confirm LCA as the underlying disorder, genetic testing is mandatory. More than 20 different genes have been linked with the pathogenesis of LCA (most important being GUCY2D and RPE65), and a detailed evaluation of respective genes is helpful in determining the exact mutations that have led to LCA [1] [2] [3] [4] [6].

Central Scotoma
  • Visual field testing shows an enlarging central scotoma. Fluorescein angiography may be useful in the acute phase.[patient.info]


  • Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates.[ncbi.nlm.nih.gov]
  • […] in the LCA2 gene therapy clinical trial clearly showed a stability of improvement in visual and retinal function that had been achieved a few months after treatment.[ncbi.nlm.nih.gov]
  • RESULTS: All patients tolerated subretinal injections and there were no treatment-related serious adverse events.[ncbi.nlm.nih.gov]
  • To determine the treatment potential in Leber congenital amaurosis (LCA) resulting from an RPGRIP1 (retinitis pigmentosa GTPase regulating-interacting protein 1) mutation, a form of LCA with recent gene therapy success in an animal model.[ncbi.nlm.nih.gov]
  • KEYWORDS: Causal genes; Leber congenital amaurosis (LCA); disease subtypes; emerging treatment options[ncbi.nlm.nih.gov]


  • […] and Causes The prognosis varies depending on the symptoms of the stage or type.[proschool.weebly.com]
  • Prognosis - Leber congenital amaurosis Not supplied. Treatment - Leber congenital amaurosis Resources - Leber congenital amaurosis Not supplied.[checkorphan.org]
  • Diagnosis and Prognosis: The diagnosis requires an eye examination by an ophthalmologist.[disorders.eyes.arizona.edu]
  • Long term visual prognosis remains to be defined. Visual acuity in patients with LCA is usually limited to the level of counting fingers or detecting hand motions or bright lights. Some patients are also extremely sensitive to light (photophobia).[provisu.ch]


  • Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.[ncbi.nlm.nih.gov]
  • To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology.[ncbi.nlm.nih.gov]
  • […] factor by some authors.1214 Therefore, the etiology of keratoconus may have a genetic and an environmental component.[healio.com]
  • Etiology To date, mutations in genes encoding retina specific proteins have been reported to cause LCA.[orpha.net]


  • Author information 1 National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Epidemiology for Birth Defect, West China Institute of Women and Children's Health, Sichuan[ncbi.nlm.nih.gov]
  • Summary Epidemiology The prevalence of LCA is 1/50,000 - 1/33,000 live births and accounts for 5% of all retinal dystrophies and 20% of blindness in school age children.[orpha.net]
  • Summary: RPE65-associated Leber Congenital Amaurosis (LCA) EPIDEMIOLOGY 1 of 81,000 births have LCA RPE65 accounts for 8% of these SIGNS Poor fixation as an infant Nystagmus Eye rubbing (Oculodigital reflex) Keratoconus Pink disks Sluggish pupils Variable[eyerounds.org]
Sex distribution
Age distribution


  • Until now, however, little was known about the pathophysiology of the disease, but LCA is usually regarded as the consequence of either impaired development of photoreceptors or extremely early degeneration of cells that have developed normally.[ncbi.nlm.nih.gov]
  • We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention.[ncbi.nlm.nih.gov]
  • In order to study the pathophysiology of the intronic CEP290 mutation, we generated two humanized knock-in mouse models each carrying 6.3 kb of the human CEP290 gene, either with or without the intronic mutation.[ncbi.nlm.nih.gov]
  • Hamel Laboratoire de Biochimie Génétique, Institut de Biologic, Montpellier, France Corinne Bareil & Mireille Claustres Pathophysiology of Vision, University Eye Hospital, Tübingen, Germany Eberhart Zrenner Cabinet d'Opthalmologie, 6, rue Saint Clair,[doi.org]


  • Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration.[ncbi.nlm.nih.gov]
  • We found that systemic injection of an ER chemical chaperone, tauroursodeoxycholic acid (TUDCA), is effective in reducing ER stress, preventing apoptosis, and preserving cones in Lrat (-/-) mice.[ncbi.nlm.nih.gov]
  • Using this model, we evaluated if gene replacement therapy using recent advancements in adeno-associated viral vectors (AAV) provides advantages in preventing rapid retinal degeneration.[ncbi.nlm.nih.gov]
  • Leber's amaurosis, Congenital retinal blindness, Congenital absence of the rods and cones, Leber's congenital tapetoretinal degeneration, LCA Symptoms - Leber congenital amaurosis Causes - Leber congenital amaurosis Prevention - Leber congenital amaurosis[checkorphan.org]



  1. Wang H, den Hollander AI, Moayedi Y, et al. Mutations in SPATA7 Cause Leber Congenital Amaurosis and Juvenile Retinitis Pigmentosa. Am J Hum Genet. 2009;84(3):380-387.
  2. Chacon-Camacho OF, Zenteno JC. Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015;3(2):112-124.
  3. Simonelli F, Maguire AM, Testa F, et al. Gene Therapy for Leber’s Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration. Mol Ther. 2010;18(3):643-650.
  4. Pennesi ME, Stover NB, Stone EM, Chiang P-W, Weleber RG. Residual Electroretinograms in Young Leber Congenital Amaurosis Patients with Mutations of AIPL1. Invest Ophthalmol Vis Sci. 2011;52(11):8166-8173.
  5. McAnany JJ, Genead MA, Walia S, et al. Visual Acuity Changes in Patients with Leber Congenital Amaurosis (LCA) and Mutations in the CEP290 Gene. JAMA Ophthalmol. 2013;131(2):178-182.
  6. 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;48:4284–4290.
  7. Yzer S, den Hollander AI, Lopez I, et al. Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290. Mol Vis. 2012;18:412-425.

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Last updated: 2019-06-28 10:01