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Leber congenital amaurosis 17(LCA17)

MedGen UID:
811616
Concept ID:
C3715164
Disease or Syndrome
Synonym: LCA17
 
Gene (location): GDF6 (8q22.1)
 
Monarch Initiative: MONDO:0014145
OMIM®: 615360

Definition

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.

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.

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.

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. [from MedlinePlus Genetics]

Clinical features

From HPO
Ultra-low vision with retained motion projection
MedGen UID:
1696685
Concept ID:
C5139241
Finding
Ultra-low vision but with retained ability to identify a moving object (typically hand motion at distance of 30 cm).

Professional guidelines

PubMed

Xiao X, Sun W, Li S, Jia X, Zhang Q
Mol Vis 2019;25:821-833. Epub 2019 Dec 2 PMID: 31908400Free PMC Article
Yi Z, Xiao X, Li S, Sun W, Zhang Q
Exp Eye Res 2019 Dec;189:107846. Epub 2019 Oct 15 doi: 10.1016/j.exer.2019.107846. PMID: 31626798
Campa C, Gallenga CE, Bolletta E, Perri P
Curr Gene Ther 2017;17(3):194-213. doi: 10.2174/1566523217666171116170040. PMID: 29149824

Recent clinical studies

Etiology

Daich Varela M, Jeste M, de Guimaraes TAC, Mahroo OA, Arno G, Webster AR, Michaelides M
Am J Ophthalmol 2024 Oct;266:255-263. Epub 2024 May 19 doi: 10.1016/j.ajo.2024.05.007. PMID: 38768745
Thanitcul C, Varadaraj V, Canner JK, Woreta FA, Soiberman US, Srikumaran D
Am J Ophthalmol 2021 Nov;231:11-18. Epub 2021 May 26 doi: 10.1016/j.ajo.2021.05.013. PMID: 34048803
Wang X, Yu C, Tzekov RT, Zhu Y, Li W
Orphanet J Rare Dis 2020 Feb 14;15(1):49. doi: 10.1186/s13023-020-1304-1. PMID: 32059734Free PMC Article
Brecelj J, Stirn-Kranjc B
Eye (Lond) 1999;13 ( Pt 1):47-54. doi: 10.1038/eye.1999.10. PMID: 10396384
Camuzat A, Dollfus H, Rozet JM, Gerber S, Bonneau D, Bonnemaison M, Briard ML, Dufier JL, Ghazi I, Leowski C
Hum Mol Genet 1995 Aug;4(8):1447-52. doi: 10.1093/hmg/4.8.1447. PMID: 7581387

Diagnosis

Daich Varela M, Jeste M, de Guimaraes TAC, Mahroo OA, Arno G, Webster AR, Michaelides M
Am J Ophthalmol 2024 Oct;266:255-263. Epub 2024 May 19 doi: 10.1016/j.ajo.2024.05.007. PMID: 38768745
Radha Rama Devi A, Naushad SM, Lingappa L
Pediatr Neurol 2020 May;106:43-49. Epub 2020 Feb 4 doi: 10.1016/j.pediatrneurol.2020.01.012. PMID: 32139166
Weisschuh N, Feldhaus B, Khan MI, Cremers FPM, Kohl S, Wissinger B, Zobor D
PLoS One 2018;13(12):e0205380. Epub 2018 Dec 21 doi: 10.1371/journal.pone.0205380. PMID: 30576320Free PMC Article
Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA
Nat Genet 2012 Sep;44(9):1040-5. Epub 2012 Jul 29 doi: 10.1038/ng.2361. PMID: 22842227Free PMC Article
Coppieters F, De Wilde B, Lefever S, De Meester E, De Rocker N, Van Cauwenbergh C, Pattyn F, Meire F, Leroy BP, Hellemans J, Vandesompele J, De Baere E
Genet Med 2012 Jun;14(6):576-85. Epub 2012 Jan 26 doi: 10.1038/gim.2011.51. PMID: 22261762

Therapy

Wang X, Yu C, Tzekov RT, Zhu Y, Li W
Orphanet J Rare Dis 2020 Feb 14;15(1):49. doi: 10.1186/s13023-020-1304-1. PMID: 32059734Free PMC Article
Shivanna M, Anand M, Chakrabarti S, Khanna H
Curr Med Chem 2019;26(17):3120-3131. doi: 10.2174/0929867325666180917102557. PMID: 30221600Free PMC Article
Weisschuh N, Feldhaus B, Khan MI, Cremers FPM, Kohl S, Wissinger B, Zobor D
PLoS One 2018;13(12):e0205380. Epub 2018 Dec 21 doi: 10.1371/journal.pone.0205380. PMID: 30576320Free PMC Article
Campa C, Gallenga CE, Bolletta E, Perri P
Curr Gene Ther 2017;17(3):194-213. doi: 10.2174/1566523217666171116170040. PMID: 29149824
Dalkara D, Sahel JA
C R Biol 2014 Mar;337(3):185-92. Epub 2014 Mar 11 doi: 10.1016/j.crvi.2014.01.002. PMID: 24702845

Prognosis

Thanitcul C, Varadaraj V, Canner JK, Woreta FA, Soiberman US, Srikumaran D
Am J Ophthalmol 2021 Nov;231:11-18. Epub 2021 May 26 doi: 10.1016/j.ajo.2021.05.013. PMID: 34048803
Wang S, Zhang Q, Zhang X, Wang Z, Zhao P
Graefes Arch Clin Exp Ophthalmol 2016 Nov;254(11):2227-2238. Epub 2016 Jul 16 doi: 10.1007/s00417-016-3428-5. PMID: 27422788
Xu Y, Xiao X, Li S, Jia X, Xin W, Wang P, Sun W, Huang L, Guo X, Zhang Q
Exp Eye Res 2016 Aug;149:93-99. Epub 2016 Jun 30 doi: 10.1016/j.exer.2016.06.019. PMID: 27375279
Chen Y, Zhang Q, Shen T, Xiao X, Li S, Guan L, Zhang J, Zhu Z, Yin Y, Wang P, Guo X, Wang J, Zhang Q
Invest Ophthalmol Vis Sci 2013 Jun 26;54(6):4351-7. doi: 10.1167/iovs.13-11606. PMID: 23661368
Brecelj J, Stirn-Kranjc B
Eye (Lond) 1999;13 ( Pt 1):47-54. doi: 10.1038/eye.1999.10. PMID: 10396384

Clinical prediction guides

Kim DG, Joo K, Han J, Choi M, Kim SW, Park KH, Park SJ, Lee CS, Byeon SH, Woo SJ
Genes (Basel) 2023 May 8;14(5) doi: 10.3390/genes14051057. PMID: 37239417Free PMC Article
Thanitcul C, Varadaraj V, Canner JK, Woreta FA, Soiberman US, Srikumaran D
Am J Ophthalmol 2021 Nov;231:11-18. Epub 2021 May 26 doi: 10.1016/j.ajo.2021.05.013. PMID: 34048803
Radha Rama Devi A, Naushad SM, Lingappa L
Pediatr Neurol 2020 May;106:43-49. Epub 2020 Feb 4 doi: 10.1016/j.pediatrneurol.2020.01.012. PMID: 32139166
Wang S, Zhang Q, Zhang X, Wang Z, Zhao P
Graefes Arch Clin Exp Ophthalmol 2016 Nov;254(11):2227-2238. Epub 2016 Jul 16 doi: 10.1007/s00417-016-3428-5. PMID: 27422788
Chen Y, Zhang Q, Shen T, Xiao X, Li S, Guan L, Zhang J, Zhu Z, Yin Y, Wang P, Guo X, Wang J, Zhang Q
Invest Ophthalmol Vis Sci 2013 Jun 26;54(6):4351-7. doi: 10.1167/iovs.13-11606. PMID: 23661368

Recent systematic reviews

Wang X, Yu C, Tzekov RT, Zhu Y, Li W
Orphanet J Rare Dis 2020 Feb 14;15(1):49. doi: 10.1186/s13023-020-1304-1. PMID: 32059734Free PMC Article

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