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Leber optic atrophy, susceptibility to(LOAM; LOAS)

MedGen UID:
374333
Concept ID:
C1839891
Finding
Synonyms: LEBER HEREDITARY OPTIC NEUROPATHY, MODIFIER OF; LHON, MODIFIER OF
 
Gene (location): PRICKLE3 (Xp11.23)
 
Monarch Initiative: MONDO:0010640
OMIM®: 308905

Definition

Leber optic atrophy, also known as Leber hereditary optic atrophy (LHON; 535000), is characterized by bilateral, painless, subacute central vision loss in young adults resulting from primary degeneration of retinal ganglion cells (RGCs) accompanied by ascending optic atrophy (summary by Yu et al., 2020). Variation in mitochondrial DNA (mtDNA) contributes to the pathogenesis of the disease. Modifier of Leber optic atrophy (LOAM) exhibits increased penetrance and earlier age of onset compared to Leber optic atrophy caused by the LHON11778A mutation in the MTND4 gene (516003.0001) alone, due to the action of mutation in PRICKLE3 as a modifier of expression of the disease. For a general description and discussion of genetic heterogeneity of Leber optic atrophy, see 535000. [from OMIM]

Clinical features

From HPO
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Leber optic atrophy
MedGen UID:
182973
Concept ID:
C0917796
Disease or Syndrome
Leber hereditary optic neuropathy (LHON) typically presents in young adults as bilateral, painless, subacute visual failure. The peak age of onset in LHON is in the second and third decades of life, with 90% of those who lose their vision doing so before age 50 years. Very rarely, individuals first manifest LHON in the seventh and eighth decades of life. Males are four to five times more likely to be affected than females, but neither sex nor mutational status significantly influences the timing and severity of the initial visual loss. Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in the general population. Some individuals with LHON, usually women, may also develop a multiple sclerosis-like illness.

Professional guidelines

PubMed

Newman NJ, Yu-Wai-Man P, Biousse V, Carelli V
Lancet Neurol 2023 Feb;22(2):172-188. Epub 2022 Sep 22 doi: 10.1016/S1474-4422(22)00174-0. PMID: 36155660
Gilhooley MJ, Owen N, Moosajee M, Yu Wai Man P
Genes (Basel) 2021 Jan 22;12(2) doi: 10.3390/genes12020147. PMID: 33499292Free PMC Article
Johns DR, Colby KA
Semin Ophthalmol 2002 Mar;17(1):33-8. doi: 10.1076/soph.17.1.33.10288. PMID: 15513454

Recent clinical studies

Etiology

Kogachi K, Ter-Zakarian A, Asanad S, Sadun A, Karanjia R
Mitochondrion 2019 May;46:270-277. Epub 2018 Aug 4 doi: 10.1016/j.mito.2018.07.007. PMID: 30081212
Zhang Y, Tian Z, Yuan J, Liu C, Liu HL, Ma SQ, Li B
Curr Gene Ther 2017;17(4):320-326. doi: 10.2174/1566523218666171129204926. PMID: 29189152Free PMC Article
Majander A, Bowman R, Poulton J, Antcliff RJ, Reddy MA, Michaelides M, Webster AR, Chinnery PF, Votruba M, Moore AT, Yu-Wai-Man P
Br J Ophthalmol 2017 Nov;101(11):1505-1509. Epub 2017 Mar 17 doi: 10.1136/bjophthalmol-2016-310072. PMID: 28314831
Yu-Wai-Man P, Votruba M, Burté F, La Morgia C, Barboni P, Carelli V
Acta Neuropathol 2016 Dec;132(6):789-806. Epub 2016 Sep 30 doi: 10.1007/s00401-016-1625-2. PMID: 27696015Free PMC Article
Neuhann T, Rautenstrauss B
Expert Rev Neurother 2013 Apr;13(4):357-67. doi: 10.1586/ern.13.19. PMID: 23545052

Diagnosis

Newman NJ, Yu-Wai-Man P, Biousse V, Carelli V
Lancet Neurol 2023 Feb;22(2):172-188. Epub 2022 Sep 22 doi: 10.1016/S1474-4422(22)00174-0. PMID: 36155660
Gilhooley MJ, Owen N, Moosajee M, Yu Wai Man P
Genes (Basel) 2021 Jan 22;12(2) doi: 10.3390/genes12020147. PMID: 33499292Free PMC Article
Jankauskaitė E, Ambroziak AM, Hajieva P, Ołdak M, Tońska K, Korwin M, Bartnik E, Kodroń A
J Appl Genet 2020 May;61(2):195-203. Epub 2020 Mar 10 doi: 10.1007/s13353-020-00550-y. PMID: 32157656Free PMC Article
Majander A, Bowman R, Poulton J, Antcliff RJ, Reddy MA, Michaelides M, Webster AR, Chinnery PF, Votruba M, Moore AT, Yu-Wai-Man P
Br J Ophthalmol 2017 Nov;101(11):1505-1509. Epub 2017 Mar 17 doi: 10.1136/bjophthalmol-2016-310072. PMID: 28314831
Johns DR, Colby KA
Semin Ophthalmol 2002 Mar;17(1):33-8. doi: 10.1076/soph.17.1.33.10288. PMID: 15513454

Therapy

Lopez Sanchez MI, Crowston JG, Mackey DA, Trounce IA
Pharmacol Ther 2016 Sep;165:132-52. Epub 2016 Jun 8 doi: 10.1016/j.pharmthera.2016.06.004. PMID: 27288727
Sanchez RN, Smith AJ, Carelli V, Sadun AA, Keltner JL
J Neuroophthalmol 2006 Dec;26(4):268-72. doi: 10.1097/01.wno.0000249320.27110.ab. PMID: 17204920
Zhou X, Wei Q, Yang L, Tong Y, Zhao F, Lu C, Qian Y, Sun Y, Lu F, Qu J, Guan MX
Biochem Biophys Res Commun 2006 Feb 3;340(1):69-75. Epub 2005 Dec 6 doi: 10.1016/j.bbrc.2005.11.150. PMID: 16364244
Qu J, Li R, Tong Y, Hu Y, Zhou X, Qian Y, Lu F, Guan MX
Biochem Biophys Res Commun 2005 Mar 25;328(4):1139-45. doi: 10.1016/j.bbrc.2005.01.062. PMID: 15707996
Peters U, Preisler-Adams S, Lanvers-Kaminsky C, Jürgens H, Lamprecht-Dinnesen A
Anticancer Res 2003 Mar-Apr;23(2B):1249-55. PMID: 12820379

Prognosis

Zhou L, Chan JCY, Chupin S, Gueguen N, Desquiret-Dumas V, Koh SK, Li J, Gao Y, Deng L, Verma C, Beuerman RW, Chan ECY, Milea D, Reynier P
Int J Mol Sci 2020 Apr 24;21(8) doi: 10.3390/ijms21083027. PMID: 32344771Free PMC Article
Jankauskaitė E, Ambroziak AM, Hajieva P, Ołdak M, Tońska K, Korwin M, Bartnik E, Kodroń A
J Appl Genet 2020 May;61(2):195-203. Epub 2020 Mar 10 doi: 10.1007/s13353-020-00550-y. PMID: 32157656Free PMC Article
Majander A, Bowman R, Poulton J, Antcliff RJ, Reddy MA, Michaelides M, Webster AR, Chinnery PF, Votruba M, Moore AT, Yu-Wai-Man P
Br J Ophthalmol 2017 Nov;101(11):1505-1509. Epub 2017 Mar 17 doi: 10.1136/bjophthalmol-2016-310072. PMID: 28314831
Yu-Wai-Man P, Griffiths PG, Chinnery PF
Prog Retin Eye Res 2011 Mar;30(2):81-114. Epub 2010 Nov 26 doi: 10.1016/j.preteyeres.2010.11.002. PMID: 21112411Free PMC Article
Johns DR, Colby KA
Semin Ophthalmol 2002 Mar;17(1):33-8. doi: 10.1076/soph.17.1.33.10288. PMID: 15513454

Clinical prediction guides

Chen Y, Wei X, Ci X, Ji Y, Zhang J
Gene 2024 Dec 20;930:148853. Epub 2024 Aug 13 doi: 10.1016/j.gene.2024.148853. PMID: 39147111
Zhou L, Chan JCY, Chupin S, Gueguen N, Desquiret-Dumas V, Koh SK, Li J, Gao Y, Deng L, Verma C, Beuerman RW, Chan ECY, Milea D, Reynier P
Int J Mol Sci 2020 Apr 24;21(8) doi: 10.3390/ijms21083027. PMID: 32344771Free PMC Article
Majander A, Bowman R, Poulton J, Antcliff RJ, Reddy MA, Michaelides M, Webster AR, Chinnery PF, Votruba M, Moore AT, Yu-Wai-Man P
Br J Ophthalmol 2017 Nov;101(11):1505-1509. Epub 2017 Mar 17 doi: 10.1136/bjophthalmol-2016-310072. PMID: 28314831
Neuhann T, Rautenstrauss B
Expert Rev Neurother 2013 Apr;13(4):357-67. doi: 10.1586/ern.13.19. PMID: 23545052
Yu-Wai-Man P, Griffiths PG, Chinnery PF
Prog Retin Eye Res 2011 Mar;30(2):81-114. Epub 2010 Nov 26 doi: 10.1016/j.preteyeres.2010.11.002. PMID: 21112411Free PMC Article

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