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Genetische Diagnostik von Schlafstörungen

Genetic diagnostics of sleep disorders

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Somnologie - Schlafforschung und Schlafmedizin Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Die genetischen Grundlagen von Schlafstörungen sind vielfältig. Bei den allermeisten Formen der Schlafstörungen als multifaktoriell bedingte Erkrankung ist nicht zu erwarten, dass Einzelgendefekte im Sinne mendelischer Vererbung für die Erkrankung als Kandidatengene verantwortlich sind. Die Entdeckung einzelner monogenetisch bedingter Assoziationen zu Schlafstörungen wird somit auch in Zukunft eine Seltenheit sein. Vor diesem Hintergrund ist die molekulargenetische Diagnostik zurzeit in der Schlafmedizin ein bislang wenig genutztes diagnostisches Instrument.

Ziel der Arbeit

Dieser Beitrag möchte einen Überblick vermitteln über die molekulargenetischen Befunden einerseits, die bereits eine relevante Wertigkeit in der Diagnosestellung von einzelnen Schlafstörungen haben, und die molekulargenetischen Befunde andererseits, die im Kontext mit den klinischen und elektrophysiologischen (polysomnographischen) Befunden dazu beitragen können, eine vermutete Diagnose zu bestärken.

Ergebnisse und Diskussion

Die bis heute bekannten HLA-Assoziationen bei der Narkolepsie und eingeschränkt beim Schlafwandeln und dem Kleine-Levin-Syndrom geben die Möglichkeit, durch die molekulargenetische Diagnostik eine zusätzliche Evidenz auf dem Boden der objektivierbaren Diagnosefindung zu haben.

Für die Gruppe des Restless-legs-Syndroms und der periodischen Beinbewegungen sowie für die in der Schlafmedizin häufigste diagnostizierte Form der schlafbezogenen Atmungsstörung, dem obstruktiven Schlaf-Apnoe-Syndrom, spielen molekulargenetische diagnostische Methoden bislang keine Rolle. Es gibt jedoch viele Befunde aus großen Kohorten bezüglich der Assoziation zu verschiedenen Genen, deren biologische Wertigkeit bislang nicht gut verstanden wird.

Für den klinisch tätigen Schlafmediziner dient somit das Wissen um die genetischen Ursachen von Schlafstörungen in erster Linie dem besseren Verständnis der Biologie. Hierzu gehören insbesondere die Insomnien und Hypersomnien, mit Ausnahme der Narkolepsie.

Eine für das bessere molekularbiologische Verständnis dieser Erkrankungen relevante Gruppe von Genen ist die Gruppe der Clock-Gene, für die erste Befunde zur unterschiedlichen Expression bei der idiopathischen Hypersomnie vorliegen.

Abstract

Background

The genetic foundations of sleep disorders are manifold. Most forms of sleep disorder are multifactorial diseases and single gene defects are not expected to be responsible as candidate genes in the sense of Mendelian inheritance of the disease. The discovery of isolated monogenetic associations to sleep disorders will also be a rarity even in the future. Against this background, molecular genetic diagnostics are currently a little used diagnostic instrument in sleep medicine.

Objectives

This article presents an overview of the molecular genetic results, which already have a relevant importance in the diagnostics of isolated sleep disorders and molecular genetic results which can contribute to strengthening a suspected diagnosis in the context of the clinical and electrophysiological (polysomnography) results.

Results and discussion

The well-known association of HLA loci with narcolepsy and the less significant association of HLA loci to other sleep disorders, such as sleepwalking and the Kleine–Levin syndrome may help to strengthen the diagnostic evidence to differentiate them from other possible diagnoses. For the group consisting of restless legs syndrome, periodic limb movements and the most commonly diagnosed form of sleep-related disorders, obstructive sleep apnea syndrome, molecular genetic findings do not have any diagnostic impact: however, there are many findings from large cohorts relating to associations with various genes but the biological significance is not yet fully understood. For clinicians working in the field of sleep medicine the molecular genetic findings concerning these sleep disorders are mainly important to obtain a better understanding of the biology, such as in insomnia and hypersomnia with the exception of narcolepsy. The group of clock genes may be of interest to better understand the biological basis of these sleep disorders as data on differential expression in idiopathic hypersomnia are available.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. P. Young gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Department für Neurologie, Klinik für Schlafmedizin und Neuromuskuläre Erkrankungen, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A 1, 48149, Münster, Deutschland

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Young, P. Genetische Diagnostik von Schlafstörungen. Somnologie 18, 218–224 (2014). https://doi.org/10.1007/s11818-014-0687-4

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