Hereditäre Bewegungsstörungen

  • Jörg B. Schulz
  • für das German Network of Hereditary Movement Disorders Ge Ne Move, Universität Göttingen, BRD
Leitthema: Seltene Krankheiten, Teil 1

Zusammenfassung

Die vererbten Bewegungsstörungen umfassen eine Gruppe genetisch determinierter Erkrankungen, die klinisch durch eine fehlende Kontrolle von Bewegungsabläufen, Gleichgewichtsstörungen und/ oder einer Spastik der Muskulatur charakterisiert sind. Die Betroffenen sind behindert, und ihre Lebensqualität ist stark eingeschränkt. Häufig ist die Lebenserwartung verkürzt. Für viele dieser Erkrankungen einschließlich der Huntington- Krankheit, der Wilson-Krankheit, der Spinozerebellären Ataxien, rezessiven Ataxien, Hereditären Spastischen Paraparesen und der Hereditären Dystonien wurden eine oder mehrere genetische Ursachen identifiziert. Aufgrund ihrer charakteristischen molekularen und biochemischen Pathogenese haben diese seltenen Erkrankungen oft Modellcharakter für häufigere Erkrankungen, z. B. die Alzheimer-Krankheit oder die Parkinson-Krankheit. Innerhalb des vom Bundesministerium für Bildung und Forschung (BMBF) geförderten Netzwerks "Hereditäre Bewegungsstörungen (German Network of Hereditary Movement Disorders, GeNeMove)" wird die klinischwissenschaftliche Forschung auf dem Gebiet der seltenen erblichen Bewegungsstörungen koordiniert und die Kooperation der einzelnen deutschen Fachzentren verbessert. Dieses Projekt umfasst die standardisierte Dokumentation der Erkrankungssymptome und der Erkrankungsverläufe, die Entwicklung von Diagnostik- und Therapieleitlinien, die genetische Diagnostik und Forschung sowie die Asservierung von Proben für DNA-, Gewebe-, Liquorund Blutmaterialbanken.

Schlüsselwörter

German Network of Hereditary Movement Disorders (GeNeMove) Friedreich-Ataxie Spinozerebelläre Ataxien Wilson-Krankheit Huntington-Krankheit Hereditäre spastische Paraparesen Hereditäre Dystonien 

Hereditary movement disorders

Abstract

Hereditary movement disorders comprise a group of genetically defined diseases characterized by an impaired control of movements, ataxia and/or spasticity. Affected individuals are disabled, their quality of life significantly reduced and their life expectancy shortened. One or more genetic causes have been identified for many of these diseases, including Huntington’s disease, Wilson’s disease, spinocerebellar ataxias, recessive ataxias, hereditary spastic paraplegia and hereditary dystonias. Due to their characteristic molecular and biochemical pathogenesis, these rare diseases can often serve as models for more common disorders such as Alzheimer’s disease or Parkinson’s disease. The primary tasks of the German Network of Hereditary Movement Disorders (GeNe- Move), funded by the German Ministry for Education and Research (BMBF), are to co-ordinate basic scientific research and clinical research into rare hereditary movement disorders and to improve the cooperation between the German centers specializing in hereditary movement disorders. For each of the diseases in its scope, GeNeMove works at creating standardized documentation of symptoms and the disease’s progressive course over time; developing rating scales for clinical examinations and guidelines for therapy; improving genetic testing; fostering genetic research; and collecting samples of DNA, tissue, CSF and blood from sufferers of the disease for biobanks.

Keywords

German Network of Hereditary Movement Disorders (GeNeMove) Friedreich’s ataxia Spinocerebellar ataxias Wilson’s disease Huntington’s disease Hereditary spastic paraparesis Hereditary dystonias 

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Literatur

  1. 1.
    Campuzano V, Montermini L, Molto MD, et al. (1996) Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427PubMedCrossRefGoogle Scholar
  2. 2.
    Puccio H, Koenig M (2000) Recent advances in the molecular pathogenesis of Friedreich ataxia. Hum Mol Genet 9:887–892PubMedCrossRefGoogle Scholar
  3. 3.
    Schulz JB, Dehmer T, Schols L, et al. (2000) Oxidative stress in patients with Friedreich ataxia. Neurology 55:1719–1721PubMedGoogle Scholar
  4. 4.
    Puccio H, Koenig M (2002) Friedreich ataxia: a paradigm for mitochondrial diseases. Curr Opin Genet Dev 12:272–277PubMedCrossRefGoogle Scholar
  5. 5.
    Buyse G, Mertens L, Di Salvo G, et al. (2003) Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring. Neurology 60:1679–1681PubMedCrossRefGoogle Scholar
  6. 6.
    Rustin P (2003) The use of antioxidants in Friedreich' s ataxia treatment. Expert Opin Investig Drugs 12:569–575PubMedCrossRefGoogle Scholar
  7. 7.
    Schöls L, Bauer P, Schmidt T, et al. (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurology 3:291–304PubMedCrossRefGoogle Scholar
  8. 8.
    Evert BO, Araujo J, Vieira-Saecker AM, et al. (2006) Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation. J Neurosci 26:11474–11486PubMedCrossRefGoogle Scholar
  9. 9.
    Evert BO, Vogt IR, Vieira-Saecker AM, et al. (2003) Gene expression profiling in ataxin-3 expressing cell lines reveals distinct effects of normal and mutant ataxin-3. J Neuropathol Exp Neurol 62:1006–1018PubMedGoogle Scholar
  10. 10.
    Fink JK (2006) Hereditary spastic paraplegia. Current neurology and neuroscience reports 6:65–76PubMedCrossRefGoogle Scholar
  11. 11.
    Sauter S, Miterski B, Klimpe S, et al. (2002) Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia. Human mutation 20:127–132PubMedCrossRefGoogle Scholar
  12. 12.
    Albanese A, Barnes MP, Bhatia KP, et al. (2006) A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force. European Journal of Neurology 13:433–444PubMedCrossRefGoogle Scholar
  13. 13.
    Müller J, Kiechl S, Wenning GK, et al. (2002) The prevalence of primary dystonia in the general community. Neurology 59:941–943PubMedGoogle Scholar
  14. 14.
    Zimprich A, Grabowski M, Asmus F, et al. (2001). Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. Nat Genet 29:66–69PubMedCrossRefGoogle Scholar
  15. 15.
    Nolte D, Niemann S, Muller U (2003) Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. PNAS 100:10347–10352PubMedCrossRefGoogle Scholar
  16. 16.
    Kupsch A, Benecke R, Muller J, et al. (2006) Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 355, 1978–1990PubMedCrossRefGoogle Scholar
  17. 17.
    Walker FO (2007) Huntington's disease. Lancet 369:218–228PubMedCrossRefGoogle Scholar
  18. 18.
    Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971–983CrossRefGoogle Scholar
  19. 19.
    Ala A, Walker AP, Ashkan K, et al. (2007) Wilson's disease. Lancet 369:397–408PubMedCrossRefGoogle Scholar
  20. 20.
    Pulst SM, Nechiporuk A, Nechiporuk T, et al. (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 14:269–276PubMedCrossRefGoogle Scholar
  21. 21.
    von Hörsten S, Schmitt I, Nguyen HP, et al. (2003). Transgenic rat model of Huntington's disease. Hum Mol Genet 12:617–624PubMedCrossRefGoogle Scholar
  22. 22.
    Schöls L, Amoiridis G, Büttner T, et al. (1997) Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 42:924–932PubMedCrossRefGoogle Scholar
  23. 23.
    Klockgether T, Ludtke R, Kramer B, et al. (1998) The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 121:589–600PubMedCrossRefGoogle Scholar
  24. 24.
    Klockgether T, Skalej M, Wedekind D, et al. (1998) Autosomal dominant cerebellar ataxia type I: MRIbased volumetry of posterior fossa structures and basal ganglia in SCA1, SCA2, and SCA3. Brain 121:1687–1693PubMedCrossRefGoogle Scholar
  25. 25.
    Schulz JB, Dehmer T, Schöls L, et al. (2000) Oxidative stress in patients with Friedreich ataxia. Neurology 55:1719–1721PubMedGoogle Scholar
  26. 26.
    Schüle R, Holland-Letz T, Klimpe S, et al. (2006) The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. Neurology 67:430–434PubMedCrossRefGoogle Scholar
  27. 27.
    Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. (2006). Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66:1717–1720PubMedCrossRefGoogle Scholar
  28. 28.
    Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L, et al. (2006) Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients. Mov Disord 21:699–704PubMedCrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  • Jörg B. Schulz
    • 1
  • für das German Network of Hereditary Movement Disorders Ge Ne Move, Universität Göttingen, BRD
  1. 1.Abt. für Neurodegeneration und Neurorestaurationsforschung, Zentren für Molekularphysiologie des Gehirns (CMPB) und Neurologische MedizinUniversitätsmedizin GöttingenGöttingen

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