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Fragiles X-assoziiertes Tremor-/Ataxie-Syndrom

Fragile X-associated tremor/ataxia syndrome

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Zusammenfassung

Das fragile X-assoziierte Tremor-/Ataxie-Syndrom (FXTAS) ist eine kürzlich erstmals beschriebene neurodegenerative Erkrankung, die sowohl Männer als auch Frauen (Männer >Frauen) mit einer Prämutation des FMR1-Gens betrifft. Der Erkrankungsbeginn liegt typischerweise nach dem 50 Lebensjahr, wobei das Lebenszeitrisiko, an FXTAS zu erkranken, für Männer bei 1:3000 bis 1:6000 liegt. Klinisch stehen eine progrediente Gangataxie und ein zerebellärer Tremor im Vordergrund, die mit kognitiven Defiziten, Polyneuropathie und autonomer Dysfunktion assoziiert sind. Die Diagnose wird in der Zusammenschau des klinischen Bildes, der zerebralen Bildgebung und der genetischen Diagnostik gestellt. Aufgrund des noch geringen Bekanntheitsgrades und des variablen klinischen Erscheinungsbildes ist das FXTAS derzeit noch unterdiagnostiziert. Die Sicherung der Diagnose ist dennoch von herausragender Bedeutung für die genetische Beratung der Patienten, da deren Nachkommen ein hohes Risiko für die Erkrankung an einem fragilen X-Syndrom, einer vorzeitigen Ovarialinsuffizienz oder einem FXTAS tragen. Darüber hinaus sind zahlreiche Symptome des FXTAS einer symptomatischen Therapie zugänglich.

Summary

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently characterized adult onset neurodegenerative disorder affecting both male and female (male>female) carriers of premutation CGG repeat expansions of the FMR1 gene. Onset typically occurs after the age of 50 years with a lifetime risk of FXTAS in males of about 1 in 3,000–6,000. Core features include progressive gait ataxia and cerebellar tremor with associated features of cognitive deficits, peripheral neuropathy and dysautonomia. The diagnosis of FXTAS is established based on clinical presentation, cerebral imaging and genetic testing. Due to the still low level of awareness of FXTAS and its variable clinical picture FXTAS is substantially underdiagnosed. However, confirming the diagnosis is essential for genetic counseling of the patients as the offspring are at risk for fragile X syndrome, premature ovarian insufficiency (POI) or FXTAS. Furthermore, many features of FXTAS can be treated symptomatically.

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Authors and Affiliations

  1. Klinik für Neurologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland

    C. Finke & C.J. Ploner

  2. Medizinisch Genetisches Zentrum, München, Deutschland

    R. Horváth & E. Holinski-Feder

  3. Friedrich-Baur-Institut, Ludwig-Maximilians-Universität, München, Deutschland

    R. Horváth

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  1. C. Finke
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  2. R. Horváth
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  4. C.J. Ploner
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Correspondence to C. Finke.

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Finke, C., Horváth, R., Holinski-Feder, E. et al. Fragiles X-assoziiertes Tremor-/Ataxie-Syndrom. Nervenarzt 80, 1473–1479 (2009). https://doi.org/10.1007/s00115-009-2846-6

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