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Optic atrophy 12(OPA12)

MedGen UID:
1720703
Concept ID:
C5436534
Disease or Syndrome
Synonyms: OPA12; OPTIC ATROPHY 12
 
Gene (location): AFG3L2 (18p11.21)
 
Monarch Initiative: MONDO:0033549
OMIM®: 618977

Definition

Optic atrophy-12 (OPA12) is an autosomal dominant neurologic disorder characterized by slowly progressive visual impairment with onset usually in the first decade, although later onset has been reported. Affected individuals have impaired color vision, photophobia, pale optic discs, optic nerve atrophy, and decreased thickness of the retinal nerve fiber layer. Some patients may exhibit additional neurologic features, including impaired intellectual development, dystonia, movement disorders, or ataxia (summary by Caporali et al., 2020). For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500). [from OMIM]

Clinical features

From HPO
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
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.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Dyschromatopsia
MedGen UID:
163559
Concept ID:
C0858618
Disease or Syndrome
A form of colorblindness in which only two of the three fundamental colors can be distinguished due to a lack of one of the retinal cone pigments.
Abnormal Ishihara plate test
MedGen UID:
892574
Concept ID:
C4073059
Finding

Professional guidelines

PubMed

Amore G, Romagnoli M, Carbonelli M, Cascavilla ML, De Negri AM, Carta A, Parisi V, Di Renzo A, Schiavi C, Lenzetti C, Zenesini C, Ormanbekova D, Palombo F, Fiorini C, Caporali L, Carelli V, Barboni P, La Morgia C
Am J Ophthalmol 2024 Jun;262:114-124. Epub 2024 Jan 24 doi: 10.1016/j.ajo.2024.01.011. PMID: 38278202
Chen BS, Yu-Wai-Man P, Newman NJ
Curr Neurol Neurosci Rep 2022 Dec;22(12):881-892. Epub 2022 Nov 21 doi: 10.1007/s11910-022-01246-y. PMID: 36414808Free PMC Article
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

Recent clinical studies

Etiology

Blanch RJ, Joseph IJ, Cockerham K
Eye (Lond) 2024 Aug;38(12):2312-2318. Epub 2024 Jun 11 doi: 10.1038/s41433-024-03129-7. PMID: 38862644Free PMC Article
Amore G, Romagnoli M, Carbonelli M, Cascavilla ML, De Negri AM, Carta A, Parisi V, Di Renzo A, Schiavi C, Lenzetti C, Zenesini C, Ormanbekova D, Palombo F, Fiorini C, Caporali L, Carelli V, Barboni P, La Morgia C
Am J Ophthalmol 2024 Jun;262:114-124. Epub 2024 Jan 24 doi: 10.1016/j.ajo.2024.01.011. PMID: 38278202
Cartes-Saavedra B, Lagos D, Macuada J, Arancibia D, Burté F, Sjöberg-Herrera MK, Andrés ME, Horvath R, Yu-Wai-Man P, Hajnóczky G, Eisner V
Proc Natl Acad Sci U S A 2023 Mar 21;120(12):e2207471120. Epub 2023 Mar 16 doi: 10.1073/pnas.2207471120. PMID: 36927155Free PMC Article
Meunier I, Bocquet B, Defoort-Dhellemmes S, Smirnov V, Arndt C, Picot MC, Dollfus H, Charif M, Audo I, Huguet H, Zanlonghi X, Lenaers G
Sci Rep 2021 Sep 21;11(1):18703. doi: 10.1038/s41598-021-98150-1. PMID: 34548540Free PMC Article
Claessen H, Kvitkina T, Narres M, Trautner C, Bertram B, Icks A
Graefes Arch Clin Exp Ophthalmol 2021 May;259(5):1089-1101. Epub 2020 Sep 25 doi: 10.1007/s00417-020-04885-4. PMID: 32974733

Diagnosis

Amore G, Romagnoli M, Carbonelli M, Cascavilla ML, De Negri AM, Carta A, Parisi V, Di Renzo A, Schiavi C, Lenzetti C, Zenesini C, Ormanbekova D, Palombo F, Fiorini C, Caporali L, Carelli V, Barboni P, La Morgia C
Am J Ophthalmol 2024 Jun;262:114-124. Epub 2024 Jan 24 doi: 10.1016/j.ajo.2024.01.011. PMID: 38278202
Franchino CA, Brughera M, Baderna V, De Ritis D, Rocco A, Seneca S, Regal L, Podini P, D'Antonio M, Toro C, Quattrini A, Scalais E, Maltecca F
Brain 2024 Mar 1;147(3):1043-1056. doi: 10.1093/brain/awad340. PMID: 37804316Free PMC Article
Chen BS, Yu-Wai-Man P, Newman NJ
Curr Neurol Neurosci Rep 2022 Dec;22(12):881-892. Epub 2022 Nov 21 doi: 10.1007/s11910-022-01246-y. PMID: 36414808Free PMC Article
Couser NL, Masood MM, Aylsworth AS, Stevenson RE
Ophthalmic Genet 2017 Sep-Oct;38(5):401-412. Epub 2017 Jan 23 doi: 10.1080/13816810.2016.1247459. PMID: 28112979
Sarathi V, Shah NS
Adv Exp Med Biol 2010;685:1-8. doi: 10.1007/978-1-4419-6448-9_1. PMID: 20687490

Therapy

Jeyakumar N, Lerch M, Dale RC, Ramanathan S
Eye (Lond) 2024 Aug;38(12):2289-2301. Epub 2024 May 23 doi: 10.1038/s41433-024-03108-y. PMID: 38783085Free PMC Article
Shamsnajafabadi H, MacLaren RE, Cehajic-Kapetanovic J
Cells 2023 Aug 7;12(15) doi: 10.3390/cells12152013. PMID: 37566092Free PMC Article
Chen BS, Yu-Wai-Man P, Newman NJ
Curr Neurol Neurosci Rep 2022 Dec;22(12):881-892. Epub 2022 Nov 21 doi: 10.1007/s11910-022-01246-y. PMID: 36414808Free PMC Article
Law SK, Li T
Cochrane Database Syst Rev 2013 May 31;5(5):CD006030. doi: 10.1002/14651858.CD006030.pub3. PMID: 23728656Free PMC Article
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ
Ophthalmology 1982 Dec;89(12):1489-93. doi: 10.1016/s0161-6420(82)34612-6. PMID: 7162793

Prognosis

Jeyakumar N, Lerch M, Dale RC, Ramanathan S
Eye (Lond) 2024 Aug;38(12):2289-2301. Epub 2024 May 23 doi: 10.1038/s41433-024-03108-y. PMID: 38783085Free PMC Article
Romahn EF, Wiltgen T, Bussas M, Aly L, Wicklein R, Noll C, Berthele A, Dehmelt V, Mardin C, Zimmer C, Korn T, Hemmer B, Kirschke JS, Mühlau M, Knier B
Front Immunol 2023;14:1284986. Epub 2023 Nov 28 doi: 10.3389/fimmu.2023.1284986. PMID: 38090586Free PMC Article
Shamsnajafabadi H, MacLaren RE, Cehajic-Kapetanovic J
Cells 2023 Aug 7;12(15) doi: 10.3390/cells12152013. PMID: 37566092Free PMC Article
Shrestha P, Sitaula S, Sharma AK, Joshi P
Nepal J Ophthalmol 2021 Jan;13(25):73-81. doi: 10.3126/nepjoph.v13i1.29035. PMID: 33981100
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529

Clinical prediction guides

Jeyakumar N, Lerch M, Dale RC, Ramanathan S
Eye (Lond) 2024 Aug;38(12):2289-2301. Epub 2024 May 23 doi: 10.1038/s41433-024-03108-y. PMID: 38783085Free PMC Article
Romahn EF, Wiltgen T, Bussas M, Aly L, Wicklein R, Noll C, Berthele A, Dehmelt V, Mardin C, Zimmer C, Korn T, Hemmer B, Kirschke JS, Mühlau M, Knier B
Front Immunol 2023;14:1284986. Epub 2023 Nov 28 doi: 10.3389/fimmu.2023.1284986. PMID: 38090586Free PMC Article
Terrén I, Sandá V, Amarilla-Irusta A, Lopez-Pardo A, Sevilla A, Astarloa-Pando G, Amo L, Zenarruzabeitia O, Scorrano L, Borrego F
Front Immunol 2023;14:1211839. Epub 2023 Jul 27 doi: 10.3389/fimmu.2023.1211839. PMID: 37575238Free PMC Article
Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R; ATP1A2/A3-collaborators
Brain 2021 Jun 22;144(5):1435-1450. doi: 10.1093/brain/awab052. PMID: 33880529
Xie LL, Shi F, Tan Z, Li Y, Bode AM, Cao Y
Cancer Sci 2018 Dec;109(12):3686-3694. Epub 2018 Nov 16 doi: 10.1111/cas.13830. PMID: 30312515Free PMC Article

Recent systematic reviews

Blanch RJ, Joseph IJ, Cockerham K
Eye (Lond) 2024 Aug;38(12):2312-2318. Epub 2024 Jun 11 doi: 10.1038/s41433-024-03129-7. PMID: 38862644Free PMC Article
Woreta FA, Lindsley KB, Gharaibeh A, Ng SM, Scherer RW, Goldberg MF
Cochrane Database Syst Rev 2023 Mar 13;3(3):CD005431. doi: 10.1002/14651858.CD005431.pub5. PMID: 36912744Free PMC Article
Matmat K, Guéant-Rodriguez RM, Oussalah A, Wiedemann-Fodé A, Dionisi-Vici C, Coelho D, Guéant JL, Conart JB
Hum Genet 2022 Jul;141(7):1239-1251. Epub 2021 Oct 15 doi: 10.1007/s00439-021-02350-8. PMID: 34652574
Law SK, Wang L, Li T
Cochrane Database Syst Rev 2020 Feb 7;2(2):CD006030. doi: 10.1002/14651858.CD006030.pub4. PMID: 32032457Free PMC Article
Law SK, Li T
Cochrane Database Syst Rev 2013 May 31;5(5):CD006030. doi: 10.1002/14651858.CD006030.pub3. PMID: 23728656Free PMC Article

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