Genetisch determinierte Dystonien

 

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Zusammenfassung

Dystonien sind durch anhaltende oder intermittierende Muskelkontraktionen gekennzeichnet, die zu abnormen, häufig repetitiven Bewegungen verschiedener Körperteile führen. Die Einteilung der Dystonien erfolgt nach klinischen und ätiologischen Kriterien, wobei insbesondere die Genetik durch die Identifikation neuer, mit der Krankheit assoziierter Gene an Bedeutung gewonnen hat.

Innerhalb des Krankheitsbildes der Dystonie können folgende Formen voneinander unterschieden werden: bei den isolierten Formen bestehen keine über die Dystonie hinausgehenden Zeichen oder Symptome; kombinierte Dystonien zeichnen sich durch eine Kombination von Dystonie und anderen Bewegungsstörungen wie Parkinsonismus, Chorea und Myoklonien aus und bei den komplexen Dystonien finden sich weitere neurologische und nicht-neurologische Manifestationen. Mutationen in den folgenden Genen sind mittlerweile als etablierte Ursachen für isolierte oder kombinierte erbliche Dystonie identifiziert worden: Tor1A, THAP1, GNAL, ANO3, KMT2B, GCH1, TAF1, PRKRA, ATP1A3, SGCE und ADCY5; > 100 Gene stehen im Zusammenhang mit komplexen Dystonien. Viele, insbesondere auch einige genetisch bedingte Formen der Dystonien, sprechen auf die Therapieoption der tiefen Hirnstimulation gut an. Aktuell arbeiten Forschungsnetzwerke daran, die Diagnostik und Therapie der Dystonien weiter zu verbessern.

Summary

Dystonias are characterized by sustained or intermittent muscle contractions resulting in abnormal and often repetitive movements of different body parts. The classification of dystonia includes clinical and etiological criteria with a particular emphasis on genetic aspects due to the identification of disease-related genes. Three following main categories of dystonia can be distinguished: isolated dystonia, in which dystonia is the only presenting sign aside from tremor, combined dystonia, in which dystonia is combined with another movement disorder such as parkinsonism, chorea or myoclonus, and complex dystonia with additional neurological and non-neurological manifestations. Mutations in the following genes have been established as cause of hereditary dystonia: Tor1A, THAP1, GNAL, ANO3, KMT2B, GCH1, TAF1, PRKRA, ATP1A3, SGCE and ADCY5; >100 genes have been implicated in complex forms of dystonia.

Therapeutic advances have particularly been achieved by the introduction of deep brain stimulation as various dystonias, including many genetic forms, exquisitely respond to this surgical procedure. Research networks currently join forces to further improve the differential diagnosis and development of causal treatment for dystonias.

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