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01.09.2009 | CME Weiterbildung · Zertifizierte Fortbildung

Hereditäre Optikusneuropathien

verfasst von: Dr. C.M. Poloschek, W.A. Lagrèze

Erschienen in: Die Ophthalmologie | Ausgabe 9/2009

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Zusammenfassung

Hereditäre Optikusneuropathien sind Erkrankungen des Sehnervs, die durch Mutationen im Kerngenom oder im mitochondrialen Genom entstehen und über eine reduzierte oxidative Phosphorylierung, Fragmentierung des mitochondrialen Netzwerks sowie Apoptoseförderung zu einem Untergang von retinalen Ganglienzellen führen. Mutationen im Kerngenom verursachen die autosomal-dominante Optikusatrophie (ADOA), autosomal-rezessive Optikusatrophien und eine X-chromosomal rezessive Form. Die Lebersche hereditäre Optikusneuropathie (LHON) wird durch Mutationen im mitochondrialen Genom ausgelöst und folgt einer maternalen Vererbung. Diagnostisch sollten eine ausführliche Anamnese und ein Stammbaum zur Klärung eines möglichen Erbgangs erhoben werden. Eine Gesichtsfelduntersuchung, ein Farbtest und eine gründliche Papillenbeurteilung sollten folgen. Wichtig ist es, im klinischen Alltag an die Differenzialdiagnose „hereditäre Optikusneuropathie“ zu denken, die aufgrund ihrer Seltenheit leicht übersehen werden kann. Die klinische Verdachtsdiagnose sollte molekulargenetisch gesichert werden, um eine möglichst genaue genetische Beratung und Prognosestellung zu gewährleisten.

Alexander C, Votruba M, Pesch UE et al (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26:211–215PubMedCrossRef

Amati-Bonneau P, Guichet A, Olichon A et al (2005) OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. Ann Neurol 58:958–963PubMedCrossRef

Amati-Bonneau P, Valentino ML, Reynier P et al (2008) OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‚plus‘ phenotypes. Brain 131:338–351PubMedCrossRef

Amati-Bonneau P, Milea D, Bonneau D et al (2009) OPA1-associated disorders: phenotypes and pathophysiology. Int J Biochem Cell Biol Apr 21. [Epub ahead of print]

Anikster Y, Kleta R, Shaag A et al (2001) Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews. Am J Hum Genet 69:1218–1224PubMedCrossRef

Assink JJ, Tijmes NT, ten Brink JB et al (1997) A gene for X-linked optic atrophy is closely linked to the Xp11.4–Xp11.2 region of the X chromosome. Am J Hum Genet 61:934–939PubMedCrossRef

Barbet F, Gerber S, Hakiki S et al (2003) A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q. Eur J Hum Genet 11:966–971PubMedCrossRef

Barbet F, Hakiki S, Orssaud C et al (2005) A third locus for dominant optic atrophy on chromosome 22q. J Med Genet 42:e1PubMedCrossRef

Barboni P, Savini G, Valentino ML et al (2006) Leber’s hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci 47:5303–5309PubMedCrossRef

10.

Baris O, Delettre C, Amati-Bonneau P et al (2003) Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy. Hum Mutat 21:656PubMedCrossRef

11.

Barnils N, Mesa E, Munoz S et al (2007) Response to idebenone and multivitamin therapy in Leber’s hereditary optic neuropathy. Arch Soc Esp Oftalmol 82:377–380PubMedCrossRef

12.

Batten B (1896) A family suffering from hereditary optic atrophy (Kjer type). Trans Ophthalmol Soc UK 16:125

13.

Beretta S, Wood JP, Derham B et al (2006) Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber hereditary optic neuropathy (LHON). Neurobiol Dis 24:308–317PubMedCrossRef

14.

Berninger TA, Jaeger W, Krastel H (1991) Electrophysiology and colour perimetry in dominant infantile optic atrophy. Br J Ophthalmol 75:49–52PubMedCrossRef

15.

Brown MD, Wallace DC (1994) Molecular basis of mitochondrial DNA disease. J Bioenerg Biomembr 26:273–289PubMedCrossRef

16.

Brown MD, Trounce IA, Jun AS et al (2000) Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber’s hereditary optic neuropathy mitochondrial DNA mutation. J Biol Chem 275:39.831–39.836

17.

Carelli V, Ross-Cisneros FN, Sadun AA (2004) Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res 23:53–89PubMedCrossRef

18.

Cohn AC, Toomes C, Potter C et al (2007) Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am J Ophthalmol 143:656–662PubMedCrossRef

19.

Cornille K, Milea D, Amati-Bonneau P et al (2008) Reversible optic neuropathy with OPA1 exon 5b mutation. Ann Neurol 63:667–671PubMedCrossRef

20.

Costeff H, Gadoth N, Apter N et al (1989) A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia. Neurology 39:595–597PubMed

21.

Delettre C, Lenaers G, Griffoin JM et al (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26:207–210PubMedCrossRef

22.

De Vries DD, Went LN, Bruyn GW et al (1996) Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. Am J Hum Genet 58:703–711

23.

Eliott D, Traboulsi EI, Maumenee IH (1993) Visual prognosis in autosomal dominant optic atrophy (Kjer type). Am J Ophthalmol 115:360–367PubMed

24.

Fournier AV, Damji KF, Epstein DL et al (2001) Disc excavation in dominant optic atrophy: differentiation from normal tension glaucoma. Ophthalmology 108:1595–1602PubMedCrossRef

25.

Garcin R, Raverdy P, Delthil S et al (1961) On a heredo-familial disease combining cataract, optic atrophy, extrapyramidal symptoms and certain defects of Friedreich’s disease. (Its nosological position in relation to the Behr’s syndrome, the Marinesco-Sjogren syndrome and Friedreich’s disease with ocular symptoms. Rev Neurol (Paris) 104:373–379

26.

Grutzner P (1963) Uber Diagnose und Funktionsstorungen bei der infantilen, dominant vererbten Opticusatrophie. Ber Dtsch Ophthalmol Ges 65:268–277

27.

Harding GF, Crews SJ, Pitts SM (1979) Psychophysical and visual evoked potential findings in hereditary optic atrophy. Trans Ophthalmol Soc UK 99:96–102PubMed

28.

Harding AE, Sweeney MG, Govan GG et al (1995) Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet 57:77–86PubMed

29.

Holder GE (1997) The pattern electroretinogram in anterior visual pathway dysfunction and its relationship to the pattern visual evoked potential: a personal clinical review of 743 eyes. Eye 11(Pt 6):924–934PubMed

30.

Holder GE, Votruba M, Carter AC et al (1998) Electrophysiological findings in dominant optic atrophy (DOA) linking to the OPA1 locus on chromosome 3q 28-qter. Doc Ophthalmol 95:217–228PubMedCrossRef

31.

Howell N, Bindoff LA, McCullough DA et al (1991) Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 49:939–950PubMed

32.

Hoyt CS (1980) Autosomal dominant optic atrophy. A spectrum of disability. Ophthalmology 87:245–251PubMed

33.

Jaeger W, Fruh D, Lauer HJ (1972) Types of acquired colour deficiencies caused by autosomal-dominant infantile optic atrophy. Mod Probl Ophthalmol 11:145–147PubMed

34.

Johns DR, Neufeld MJ, Park RD (1992) An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem Biophys Res Commun 187:1551–1557PubMedCrossRef

35.

Johns DR, Smith KH, Miller NR (1992) Leber’s hereditary optic neuropathy. Clinical manifestations of the 3460 mutation. Arch Ophthalmol 110:1577–1581PubMed

36.

Johns DR, Heher KL, Miller NR et al (1993) Leber’s hereditary optic neuropathy. Clinical manifestations of the 14484 mutation. Arch Ophthalmol 111:495–498PubMed

37.

Kamei S, Chen-Kuo-Chang M, Cazevieille C et al (2005) Expression of the Opa1 mitochondrial protein in retinal ganglion cells: its downregulation causes aggregation of the mitochondrial network. Invest Ophthalmol Vis Sci 46:4288–4294PubMedCrossRef

38.

Katz BJ, Zhao Y, Warner JE et al (2006) A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4–Xp11.2. Am J Med Genet A 140:2207–2211PubMed

39.

Kerrison JB, Arnould VJ, Ferraz Sallum JM et al (1999) Genetic heterogeneity of dominant optic atrophy, Kjer type: identification of a second locus on chromosome 18q12.2–12.3. Arch Ophthalmol 117:805–810PubMed

40.

Kerrison JB, Miller NR, Hsu F et al (2000) A case-control study of tobacco and alcohol consumption in Leber hereditary optic neuropathy. Am J Ophthalmol 130:803–812PubMedCrossRef

41.

Kjer P (1956) Hereditary infantile optic atrophy with dominant transmission; preliminary report. Dan Med Bull 3:135–141PubMed

42.

Kjer P (1959) Infantile optic atrophy with dominant mode of inheritance: a clinical and genetic study of 19 Danish families. Acta Ophthalmol Suppl 164:1–147PubMed

43.

Kjer P, Jensen OA, Klinken L (1983) Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy. Acta Ophthalmol (Copenh) 61:300–312

44.

Kjer B, Eiberg H, Kjer P et al (1996) Dominant optic atrophy mapped to chromosome 3q region. II. Clinical and epidemiological aspects. Acta Ophthalmol Scand 74:3–7PubMedCrossRef

45.

Kline LB, Glaser JS (1979) Dominant optic atrophy. The clinical profile. Arch Ophthalmol 97:1680–1686PubMed

46.

Kok-van Alphen CC (1970) Four families with the dominant infantile form of optic nerve atrophy. Acta Ophthalmol (Copenh) 48:905–916

47.

Konigsmark BW, Knox DL, Hussels IE et al (1974) Dominant congenital deafness and progressive optic nerve atrophy. Occurrence in four generations of a family. Arch Ophthalmol 91:99–103PubMed

48.

Leber T (1871) Ueber hereditaere und congenital angelegte Sehnervenleiden. Graefes Arch Ophthalmol 17:249–291CrossRef

49.

Lenaers G, Reynier P, Elachouri G et al (2009) OPA1 functions in mitochondria and dysfunctions in optic nerve. Int J Biochem Cell Biol Apr 21. [Epub ahead of print]

50.

Li C, Kosmorsky G, Zhang K et al (2005) Optic atrophy and sensorineural hearing loss in a family caused by an R445H OPA1 mutation. Am J Med Genet A 138A:208–211PubMedCrossRef

51.

Lodberg CV, Lund A (1950) Hereditary optic atrophy with dominant transmission; three Danish families. Acta Ophthalmol (Copenh) 28:437–468

52.

Lodi R, Tonon C, Valentino ML et al (2004) Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. Ann Neurol 56:719–723PubMedCrossRef

53.

Macmillan C, Kirkham T, Fu K et al (1998) Pedigree analysis of French Canadian families with T14484C Leber’s hereditary optic neuropathy. Neurology 50:417–422PubMed

54.

Man PY, Griffiths PG, Brown DT et al (2003) The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am J Hum Genet 72:333–339PubMedCrossRef

55.

Manchester PT Jr, Calhoun FP Jr (1958) Dominant hereditary optic atrophy with bitemporal field defects. AMA Arch Ophthalmol 60:479–484PubMed

56.

Mantyjarvi MI, Nerdrum K, Tuppurainen K (1992) Color vision in dominant optic atrophy. J Clin Neuroophthalmol 12:98–103PubMed

57.

Martinou JC, Desagher S, Antonsson B (2000) Cytochrome c release from mitochondria: all or nothing. Nat Cell Biol 2:E41–E43PubMedCrossRef

58.

Newman NJ, Biousse V (2004) Hereditary optic neuropathies. Eye 18:1144–1160PubMedCrossRef

59.

Newman NJ, Lott MT, Wallace DC (1991) The clinical characteristics of pedigrees of Leber’s hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol 111:750–762PubMed

60.

Newman NJ, Biousse V, David R et al (2005) Prophylaxis for second eye involvement in Leber hereditary optic neuropathy: an open-labeled, nonrandomized multicenter trial of topical brimonidine purite. Am J Ophthalmol 140:407–415PubMed

61.

Nicolaides P, Appleton RE, Fryer A (1996) Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome. J Med Genet 33:419–421PubMedCrossRef

62.

Nikoskelainen E, Sogg RL, Rosenthal AR et al (1977) The early phase in Leber hereditary optic atrophy. Arch Ophthalmol 95:969–978PubMed

63.

Nikoskelainen EK, Huoponen K, Juvonen V et al (1996) Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology 103:504–514PubMed

64.

Nochez Y, Arsene S, Gueguen N et al (2009) Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect. Mol Vis 15:598–608PubMed

65.

Payne M, Yang Z, Katz BJ et al (2004) Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. Am J Ophthalmol 138:749–755PubMedCrossRef

66.

Puomila A, Hamalainen P, Kivioja S et al (2007) Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland. Eur J Hum Genet 15:1079–1089PubMedCrossRef

67.

Ramos Cdo V, Bellusci C, Savini G et al (2009) Association of optic disc size with development and prognosis of Leber’s hereditary optic neuropathy. Invest Ophthalmol Vis Sci 50:1666–1674PubMedCrossRef

68.

Reynier P, Amati-Bonneau P, Verny C et al (2004) OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. J Med Genet 41:e110PubMedCrossRef

69.

Riordan-Eva P, Sanders MD, Govan GG et al (1995) The clinical features of Leber’s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 118(Pt 2):319–337PubMedCrossRef

70.

Ryan S, Arden GB, Weinstein GW (1989) Electrophysiological discrimination between retinal and optic nerve disorders. Metab Pediatr Syst Ophthalmol 12:69–73PubMed

71.

Sadun AA, Salomao SR, Berezovsky A et al (2006) Subclinical carriers and conversions in Leber hereditary optic neuropathy: a prospective psychophysical study. Trans Am Ophthalmol Soc 104:51–61PubMed

72.

Savini G, Barboni P, Valentino ML et al (2005) Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber’s hereditary optic neuropathy mutations. Ophthalmology 112:127–131PubMedCrossRef

73.

Seedorff T (1985) The inheritance of Leber’s disease. A genealogical follow-up study. Acta Ophthalmol (Copenh) 63:135–145

74.

Shankar SP, Fingert JH, Carelli V et al (2008) Evidence for a novel x-linked modifier locus for Leber hereditary optic neuropathy. Ophthalmic Genet 29:17–24PubMedCrossRef

75.

Smith DP (1972) Diagnostic criteria in cominantly inherited juvenile optic atrophy. A report of three new families. Am J Optom Arch Am Acad Optom 49:183–200PubMed

76.

Smith JL, Hoyt WF, Susac JO (1973) Ocular fundus in acute Leber optic neuropathy. Arch Ophthalmol 90:349–354PubMed

77.

Smith KH, Johns DR, Heher KL et al (1993) Heteroplasmy in Leber’s hereditary optic neuropathy. Arch Ophthalmol 111:1486–1490PubMed

78.

Snell S (1897) Disease of the optic nerve. I. Hereditary or congenital optic atrophy and allied cases. Trans Ophthalmol Soc UK 17:66–81

79.

Sorajja P, Sweeney MG, Chalmers R et al (2003) Cardiac abnormalities in patients with Leber’s hereditary optic neuropathy. Heart 89:791–792PubMedCrossRef

80.

Sugisaka E, Ohde H, Shinoda K et al (2007) Woman with atypical unilateral Leber’s hereditary optic neuropathy with visual improvement. Clin Experiment Ophthalmol 35:868–870PubMed

81.

Treft RL, Sanborn GE, Carey J et al (1984) Dominant optic atrophy, deafness, ptosis, ophthalmoplegia, dystaxia, and myopathy. A new syndrome. Ophthalmology 91:908–915PubMed

82.

Verny C, Loiseau D, Scherer C et al (2008) Multiple sclerosis-like disorder in OPA1-related autosomal dominant optic atrophy. Neurology 70:1152–1153PubMedCrossRef

83.

Votruba M, Fitzke FW, Holder GE et al (1998) Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthalmol 116:351–358PubMed

84.

Votruba M, Thiselton D, Bhattacharya SS (2003) Optic disc morphology of patients with OPA1 autosomal dominant optic atrophy. Br J Ophthalmol 87:48–53PubMedCrossRef

85.

Wallace DC, Singh G, Lott MT et al (1988) Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242:1427–1430PubMedCrossRef

86.

Walters JW, Gaume A, Pate L (2006) Short wavelength-automated perimetry compared with standard achromatic perimetry in autosomal dominant optic atrophy. Br J Ophthalmol 90:1267–1270PubMedCrossRef

87.

Went LN, De Vries-De Mol EC, Volker-Dieben HJ (1975) A family with apparently sex-linked optic atrophy. J Med Genet 12:94–98PubMedCrossRef

Titel: Hereditäre Optikusneuropathien
verfasst von: Dr. C.M. Poloschek
W.A. Lagrèze
Publikationsdatum: 01.09.2009
Verlag: Springer-Verlag
Erschienen in: Die Ophthalmologie / Ausgabe 9/2009
Print ISSN: 2731-720X
Elektronische ISSN: 2731-7218
DOI: https://doi.org/10.1007/s00347-009-2023-0

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