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Hereditäre Optikusneuropathien

Hereditary optic atrophies

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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.

Abstract

Hereditary optic neuropathies are caused by mutations either in the nuclear or mitochondrial genome and lead to retinal ganglion cell death mediated by reduced oxidative phosphorylation, fragmentation of the mitochondrial network, and increased sensitivity to apoptosis. Nuclear mutations result in autosomal dominant optic atrophy, autosomal recessive optic atrophy, or X-linked recessive optic atrophy, whereas mitochondrial mutations result in Leber’s hereditary optic neuropathy, which is maternally inherited. A tentative diagnosis of a hereditary optic neuropathy can usually be made on the grounds of a thorough patient and family history, visual field and color vision tests, and a detailed assessment of the optic nerve head. The rarity of hereditary optic neuropathies makes it difficult to include these disorders in the differential diagnosis. Molecular genetic testing of a blood DNA sample should be performed on every patient, with implications for future genetic counseling and prediction of the disease course.

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    C.M. Poloschek & W.A. Lagrèze

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Poloschek, C., Lagrèze, W. Hereditäre Optikusneuropathien. Ophthalmologe 106, 845–857 (2009). https://doi.org/10.1007/s00347-009-2023-0

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