Hereditäre Makuladystrophien

Zusammenfassung

Hereditäre Makuladystrophien gehören zur großen Gruppe der erblichen Netzhauterkrankungen, die durch Mutationen in spezifischen Genen bedingt sind. Sie stellen oft eine diagnostische Herausforderung dar aufgrund der relativen Seltenheit der einzelnen Krankheitsbilder, der ausgeprägten klinischen und genetischen Heterogenität, der eher unspezifischen Sehstörungen und der anfangs oft nur dezenten Fundusveränderungen. Makuladystrophien können sich in jedem Lebensalter manifestieren und beschränken sich im Krankheitsverlauf vorwiegend auf die Makularegion, wobei Fundusveränderungen bis in die mittlere Peripherie möglich sind. Je nach Schwere der zugrunde liegenden Mutation kann es in einigen Fällen zu einem Übergang in eine generalisierte Netzhautdystrophie kommen. Die alleinige Ophthalmoskopie ist zur Diagnosestellung in den meisten Fällen nicht ausreichend. Eine rasche und korrekte Diagnosestellung ist für den Patienten aber von wesentlicher Bedeutung, da er nur dann gezielt beraten, möglichen Hilfsmitteln, Förderungen und ggf. therapeutischen Optionen zugeführt werden kann. Von wesentlicher Bedeutung ist die retinale Bildgebung mit Fundusautofluoreszenz, Nah-Infrarot-Autofluoreszenz und optischer Kohärenztomografie, da diese Verfahren für die einzelnen Makuladystrophien oft charakteristische Veränderungen aufzeigen können, die funduskopisch nicht erkennbar sind. In Fällen von fehlenden morphologischen Veränderungen ist die elektrophysiologische Diagnostik essenziell und erlaubt den Nachweis einer makulären oder generalisierten Netzhautfunktionsstörung. In der molekulargenetischen Diagnostik hat es in den letzten Jahren deutliche Fortschritte gegeben. Durch die Entwicklung der Next-Generation-Sequencing-Technik können nun alle bekannten Gene für Netzhautdystrophien untersucht werden. Somit kann nun in wesentlich mehr Fällen die genetische Ursache identifiziert werden, als es früher der Fall war, wobei eine möglichst korrekte klinische Diagnose jedoch weiterhin von tragender Bedeutung und Voraussetzung für eine gezielte und erfolgreiche genetische Analyse ist. Die Bedeutung einer molekulargenetisch gesicherten Diagnose nimmt stetig zu, denn diese ist Voraussetzung für Betroffene, in Zukunft eventuell an therapeutischen Studien teilnehmen zu können.

Abstract

Hereditary macular dystrophies are part of the group of inherited retinopathies caused by mutations of specific genes. Challenging features are their rarity, enormous clinical and genetic heterogeneity, unspecific visual disturbances, and often only mild initial fundus changes. The onset of macular dystrophies may occur at any age. They manifest in the macular region, whereas fundus changes can reach the mid periphery as well. In some cases, macular dystrophy can progress into generalised retinal dystrophy, depending on the severity of the causative mutations. Funduscopy alone is often insufficient for diagnosis. However, correct diagnosis is essential for the patient for counseling, low vision aids, support, and therapeutic options. Retinal imaging, with fundus autofluorescence, near-infrared autofluorescence and optical coherence tomography, is very important, as it can show typical changes not visible on funduscopy. In cases where morphological changes are absent, retinal dysfunction must be detected by electrophysiological testing. There has been technical progress in molecular genetic testing in recent years. With the development of modern sequencing, an analysis for all known genes of hereditary retinal dystrophies has been established. The genetic defect can now be identified in more cases than before. However, a correct initial clinical diagnosis is still required for successful genetic analysis. The importance of a genetically confirmed diagnosis is increasing, as this is needed for patients who could have the chance in the near future to participate in therapeutic trials.

Schlüsselwörter

hereditäre Makuladystrophie - Fundusautofluoreszenz - Nah-Infrarot-Autofluoreszenz - optische Kohärenztomografie - Elektrophysiologie - Genetik

Key words

hereditary macular dystrophy - fundus autofluorescence - near-infrared autofluorescence - optical coherence tomography - electrophysiology - genetics

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