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Leber congenital amaurosis 3(LCA3)

MedGen UID:
346964
Concept ID:
C1858677
Disease or Syndrome
Synonyms: Amaurosis congenita of Leber, type 3; LCA3; SPATA7-Related Leber Congenital Amaurosis; SPATA7-Related Retinitis Pigmentosa
 
Gene (location): SPATA7 (14q31.3)
 
Monarch Initiative: MONDO:0011415
OMIM®: 604232

Definition

Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis, whereas the less aggressive forms are usually considered retinitis pigmentosa (Gu et al., 1997). SPATA7-associated retinopathy shows a variable age at onset, ranging from infancy to adulthood, as well as phenotypic variability, including intrafamilial differences (Wang et al., 2009; Avila-Fernandez et al., 2011; Feldhaus et al., 2018; Sengillo et al., 2018). Mackay et al. (2011) concluded that SPATA7 retinopathy is an infantile-onset severe cone-rod dystrophy with early extensive peripheral retinal atrophy but with variable foveal involvement. For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000. Reviews Kannabiran (2020) reviewed reported SPATA7 mutations and the associated phenotypes. The author noted that there were no clear-cut correlations between genotype and phenotype, and that phenotypic heterogeneity had been observed among patients with the same mutation. Clinical variability was also often seen in patients with SPATA7 mutations, with some phenotypes resembling cone-rod dystrophy or choroideremia. [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/leber-congenital-amaurosis

Clinical features

From HPO
Nyctalopia
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
Inability to see well at night or in poor light.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Constriction of peripheral visual field
MedGen UID:
68613
Concept ID:
C0235095
Finding
An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).

Professional guidelines

PubMed

Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364
Campa C, Gallenga CE, Bolletta E, Perri P
Curr Gene Ther 2017;17(3):194-213. doi: 10.2174/1566523217666171116170040. PMID: 29149824
Stein L, Roy K, Lei L, Kaushal S
Expert Opin Biol Ther 2011 Mar;11(3):429-39. doi: 10.1517/14712598.2011.557358. PMID: 21299439

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
Georgiou M, Fujinami K, Michaelides M
Clin Exp Ophthalmol 2021 Apr;49(3):270-288. Epub 2021 Mar 20 doi: 10.1111/ceo.13917. PMID: 33686777
McConnachie DJ, Stow JL, Mallett AJ
Am J Kidney Dis 2021 Mar;77(3):410-419. Epub 2020 Oct 9 doi: 10.1053/j.ajkd.2020.08.012. PMID: 33039432
Xu K, Xie Y, Sun T, Zhang X, Chen C, Li Y
Br J Ophthalmol 2020 Jul;104(7):932-937. Epub 2019 Oct 19 doi: 10.1136/bjophthalmol-2019-314281. PMID: 31630094
Ziccardi L, Cordeddu V, Gaddini L, Matteucci A, Parravano M, Malchiodi-Albedi F, Varano M
Int J Mol Sci 2019 Nov 14;20(22) doi: 10.3390/ijms20225722. PMID: 31739639Free PMC Article

Diagnosis

Georgiou M, Fujinami K, Michaelides M
Clin Exp Ophthalmol 2021 Apr;49(3):270-288. Epub 2021 Mar 20 doi: 10.1111/ceo.13917. PMID: 33686777
Cai S, Therattil A, Vajzovic L
Curr Opin Ophthalmol 2020 May;31(3):155-160. doi: 10.1097/ICU.0000000000000650. PMID: 32168002
Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364
Wang H, Wang X, Zou X, Xu S, Li H, Soens ZT, Wang K, Li Y, Dong F, Chen R, Sui R
Invest Ophthalmol Vis Sci 2015 Jun;56(6):3642-55. doi: 10.1167/iovs.14-15972. PMID: 26047050Free PMC Article
Goodwin P
Curr Opin Ophthalmol 2008 May;19(3):255-62. doi: 10.1097/ICU.0b013e3282fc27fc. PMID: 18408503

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
Gruntman AM, Flotte TR
FASEB J 2018 Apr;32(4):1733-1740. doi: 10.1096/fj.201700982R. PMID: 31282760
Dias MF, Joo K, Kemp JA, Fialho SL, da Silva Cunha A Jr, Woo SJ, Kwon YJ
Prog Retin Eye Res 2018 Mar;63:107-131. Epub 2017 Oct 31 doi: 10.1016/j.preteyeres.2017.10.004. PMID: 29097191
Dalkara D, Goureau O, Marazova K, Sahel JA
Hum Gene Ther 2016 Feb;27(2):134-47. doi: 10.1089/hum.2015.147. PMID: 26751519Free PMC Article
Stein L, Roy K, Lei L, Kaushal S
Expert Opin Biol Ther 2011 Mar;11(3):429-39. doi: 10.1517/14712598.2011.557358. PMID: 21299439

Prognosis

Hernandez CC, Gimenez LE, Dahir NS, Peisley A, Cone RD
Am J Physiol Cell Physiol 2023 Mar 1;324(3):C694-C706. Epub 2023 Jan 30 doi: 10.1152/ajpcell.00335.2022. PMID: 36717105Free PMC Article
Ma DJ, Lee HS, Kim K, Choi S, Jang I, Cho SH, Yoon CK, Lee EK, Yu HG
BMC Med Genomics 2021 Mar 10;14(1):74. doi: 10.1186/s12920-021-00874-6. PMID: 33691693Free PMC Article
Ziccardi L, Cordeddu V, Gaddini L, Matteucci A, Parravano M, Malchiodi-Albedi F, Varano M
Int J Mol Sci 2019 Nov 14;20(22) doi: 10.3390/ijms20225722. PMID: 31739639Free PMC Article
Verma IC, Paliwal P, Singh K
Indian J Pediatr 2018 Mar;85(3):228-236. Epub 2017 Oct 2 doi: 10.1007/s12098-017-2453-7. PMID: 28971364
Goodwin P
Curr Opin Ophthalmol 2008 May;19(3):255-62. doi: 10.1097/ICU.0b013e3282fc27fc. PMID: 18408503

Clinical prediction guides

Rodriguez-Martinez AC, Higgins BE, Tailor-Hamblin V, Malka S, Cheloni R, Collins AM, Bladen J, Henderson R, Moosajee M
Int J Mol Sci 2023 Sep 11;24(18) doi: 10.3390/ijms241813932. PMID: 37762234Free PMC Article
Hernandez CC, Gimenez LE, Dahir NS, Peisley A, Cone RD
Am J Physiol Cell Physiol 2023 Mar 1;324(3):C694-C706. Epub 2023 Jan 30 doi: 10.1152/ajpcell.00335.2022. PMID: 36717105Free 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
Ma DJ, Lee HS, Kim K, Choi S, Jang I, Cho SH, Yoon CK, Lee EK, Yu HG
BMC Med Genomics 2021 Mar 10;14(1):74. doi: 10.1186/s12920-021-00874-6. PMID: 33691693Free PMC Article
McKibbin M, Ali M, Mohamed MD, Booth AP, Bishop F, Pal B, Springell K, Raashid Y, Jafri H, Inglehearn CF
Arch Ophthalmol 2010 Jan;128(1):107-13. doi: 10.1001/archophthalmol.2010.309. PMID: 20065226

Recent systematic reviews

Sallum JMF, Kaur VP, Shaikh J, Banhazi J, Spera C, Aouadj C, Viriato D, Fischer MD
Adv Ther 2022 Mar;39(3):1179-1198. Epub 2022 Jan 30 doi: 10.1007/s12325-021-02036-7. PMID: 35098484Free PMC Article
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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