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Leber congenital amaurosis 10(LCA10)

MedGen UID:
346672
Concept ID:
C1857821
Disease or Syndrome
Synonyms: Amaurosis congenita of Leber, type 10; CEP290-Related Leber Congenital Amaurosis; LCA10
 
Gene (location): CEP290 (12q21.32)
 
Monarch Initiative: MONDO:0012723
OMIM®: 611755

Definition

Leber congenital amaurosis (LCA) is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life (summary by den Hollander et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000). [from OMIM]

Additional description

From MedlinePlus Genetics
In very rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. Because of the visual loss, affected children may become isolated. Providing children with opportunities to play, hear, touch, understand and other early educational interventions may prevent developmental delays in children with Leber congenital amaurosis.

A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of affected individuals poking, pressing, and rubbing their eyes with a knuckle or finger. Poking their eyes often results in the sensation of flashes of light called phosphenes. Researchers suspect that this behavior may contribute to deep-set eyes in affected children.

At least 20 genetic types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.

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.

Leber congenital amaurosis, also known as LCA, is an eye disorder that is present from birth (congenital). This condition 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 at birth or shortly afterward. The visual impairment tends to be severe and may worsen over time.  https://medlineplus.gov/genetics/condition/leber-congenital-amaurosis

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyposmia
MedGen UID:
473584
Concept ID:
C2364082
Finding
A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Professional guidelines

PubMed

Ledford H
Nature 2020 Mar;579(7798):185. doi: 10.1038/d41586-020-00655-8. PMID: 32157225

Recent clinical studies

Etiology

Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A
Nat Med 2022 May;28(5):1014-1021. Epub 2022 Apr 4 doi: 10.1038/s41591-022-01755-w. PMID: 35379979Free PMC Article

Diagnosis

Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A
Nat Med 2022 May;28(5):1014-1021. Epub 2022 Apr 4 doi: 10.1038/s41591-022-01755-w. PMID: 35379979Free PMC Article
Leroy BP, Birch DG, Duncan JL, Lam BL, Koenekoop RK, Porto FBO, Russell SR, Girach A
Retina 2021 May 1;41(5):898-907. doi: 10.1097/IAE.0000000000003133. PMID: 33595255Free PMC Article

Therapy

Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A
Nat Med 2022 May;28(5):1014-1021. Epub 2022 Apr 4 doi: 10.1038/s41591-022-01755-w. PMID: 35379979Free PMC Article
Leroy BP, Birch DG, Duncan JL, Lam BL, Koenekoop RK, Porto FBO, Russell SR, Girach A
Retina 2021 May 1;41(5):898-907. doi: 10.1097/IAE.0000000000003133. PMID: 33595255Free PMC Article

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