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Ataxia

  • Alison La Pean KirschnerEmail author
  • Jill S. Goldman
Chapter

Abstract

The hereditary ataxias are a heterogeneous group of neurological disorders characterized by imbalance, unsteady gait, uncoordinated movements, dysarthria, and, often, abnormal oculomotor control. Age of onset of these disorders ranges from infancy to late life, and may include many additional clinical features such as neuropathy, cognitive dysfunction, and parkinsonism. Genetic counseling is frequently complicated by the overlap in phenotypes, anticipation, inability to predict age of onset, and lack of treatment options. This chapter will focus on the autosomal dominant spinocerebellar ataxias (SCAs), autosomal recessive Friedreich ataxia, and X-linked Fragile X tremor ataxia syndrome.

Keywords

Genetic Testing Genetic Counselor Repeat Expansion Spinocerebellar Ataxia Premature Ovarian Failure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

Ataxia Part 1 (MOV 359973 kb)

Ataxia Part 2 (MOV 416579 kb)

References

  1. 1.
    Joo, B. E., Lee, C. N., & Park, K. W. (2012). Prevalence rate and functional status of cerebellar ataxia in Korea. Cerebellum, 11(3), 733–738.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Coutinho, P., Ruano, L., Loureiro, J. L., Cruz, V. T., Barros, J., Tuna, A., et al. (2013). Hereditary ataxia and spastic paraplegia in Portugal: A population-based prevalence study. JAMA Neurology, 70(6), 746–755.PubMedCrossRefGoogle Scholar
  3. 3.
    Erichsen, A. K., Koht, J., Stray-Pedersen, A., Abdelnoor, M., & Tallaksen, C. M. (2009). Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: A population-based study. Brain, 132(Pt 6), 1577–1588.PubMedCrossRefGoogle Scholar
  4. 4.
    Klockgether, T. (2008). The clinical diagnosis of autosomal dominant spinocerebellar ataxias. Cerebellum, 7(2), 101–105.PubMedCrossRefGoogle Scholar
  5. 5.
    Jayadev, S., & Bird, T. D. (2013). Hereditary ataxias: Overview. Genetics in Medicine, 15(9), 673–683.PubMedCrossRefGoogle Scholar
  6. 6.
    Verbeek, D. S., & van de Warrenburg, B. P. (2011). Genetics of the dominant ataxias. Seminars in Neurology, 31(5), 461–469.PubMedCrossRefGoogle Scholar
  7. 7.
    Manto, M. U. (2005). The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum, 4(1), 2–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Durr, A. (2010). Autosomal dominant cerebellar ataxias: Polyglutamine expansions and beyond. Lancet Neurology, 9(9), 885–894.CrossRefGoogle Scholar
  9. 9.
    van de Warrenburg, B. P., Sinke, R. J., Verschuuren-Bemelmans, C. C., Scheffer, H., Brunt, E. R., Ippel, P. F., et al. (2002). Spinocerebellar ataxias in the Netherlands: Prevalence and age at onset variance analysis. Neurology, 58(5), 702–708.PubMedCrossRefGoogle Scholar
  10. 10.
    Stevanin, G., Dürr, A., & Brice, A. (2000). Clinical and molecular advances in autosomal dominant cerebellar ataxias: From genotype to phenotype and physiopathology. European Journal of Human Genetics, 8(1), 4–18.PubMedCrossRefGoogle Scholar
  11. 11.
    Globas, C., du Montcel, S. T., Baliko, L., Boesch, S., Depondt, C., DiDonato, S., et al. (2008). Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Movement Disorders, 23(15), 2232–2238.PubMedCrossRefGoogle Scholar
  12. 12.
    Paulson, H. L. (2007). Dominantly inherited ataxias: Lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3. Seminars in Neurology, 27(2), 133–142.PubMedCrossRefGoogle Scholar
  13. 13.
    Bidichandani, S. I., & Delatycki, M. B. (1998). Friedreich ataxia. In R. A. Pagon, M. P. Adam, T. D. Bird, C. R. Dolan, C. T. Fong, & K. Stephens (Eds.), Source GeneReviews™ [Internet (pp. 1993–2013). Seattle, WA: University of Washington. Updated 2012 Feb 02.Google Scholar
  14. 14.
    Durr, A., Cossee, M., Agid, Y., Campuzano, V., Mignard, C., Penet, C., et al. (1996). Clinical and genetic abnormalities in patients with Friedreich’s ataxia. The New England Journal of Medicine, 335, 1169–1175.PubMedCrossRefGoogle Scholar
  15. 15.
    Harding, A. E. (1981). Friedreich’s ataxia: A clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain, 104, 589–620.PubMedCrossRefGoogle Scholar
  16. 16.
    Klockgether, T., Zühlke, C., Schulz, J. B., Bürk, K., Fetter, M., Dittmann, H., et al. (1996). Friedreich’s ataxia with retained tendon reflexes: Molecular genetics, clinical neurophysiology, and magnetic resonance imaging. Neurology, 46(1), 118–121.PubMedCrossRefGoogle Scholar
  17. 17.
    Durr, A., & Brice, A. (2000). Clinical and genetic aspects of spinocerebellar degeneration. Current Opinion in Neurology, 13(4), 407–413.PubMedCrossRefGoogle Scholar
  18. 18.
    Coppola, G., De Michele, G., Cavalcanti, F., Pianese, L., Perretti, A., Santoro, L., et al. (1999). Why do some Friedreich’s ataxia patients retain tendon reflexes? A clinical, neurophysiological and molecular study. Journal of Neurology, 246, 353–357.PubMedCrossRefGoogle Scholar
  19. 19.
    De Michele, G., Filla, A., Cavalcanti, F., Di Maio, L., Pianese, L., Castaldo, I., et al. (1994). Late onset Friedreich’s disease: Clinical features and mapping of mutation to the FRDA locus. Journal of Neurology, Neurosurgery and Psychiatry, 57(8), 977–979.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Gates, P. C., Paris, D., Forrest, S. M., Williamson, R., & Gardner, R. J. (1998). Friedreich’s ataxia presenting as adult-onset spastic paraparesis. Neurogenetics, 1, 297–299.PubMedCrossRefGoogle Scholar
  21. 21.
    Berciano, J., Combarros, O., De Castro, M., & Palau, F. (1997). Intronic GAA triplet repeat expansion in Friedreich’s ataxia presenting with pure sensory ataxia. Journal of Neurology, 244, 390–391.PubMedCrossRefGoogle Scholar
  22. 22.
    Hanna, M. G., Davis, M. B., Sweeney, M. G., Noursadeghi, M., Ellis, C. J., Elliot, P., et al. (1998). Generalized chorea in two patients harboring the Friedreich’s ataxia gene trinucleotide repeat expansion. Movement Disorders, 13, 339–340.PubMedCrossRefGoogle Scholar
  23. 23.
    La Pean, A., Jeffries, N., Grow, C., Ravina, B., & Di Prospero, N. A. (2008). Predictors of progression in patients with Friedreich ataxia. Movement Disorders, 23, 2026–2032.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Hagerman, R., & Hagerman, P. (2013). Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurology, 12(8), 786–798.PubMedCentralCrossRefGoogle Scholar
  25. 25.
    Leehey, M. A. (2009). Fragile X-associated tremor/ataxia syndrome: Clinical phenotype, diagnosis, and treatment. Journal of Investigative Medicine, 57(8), 830–836.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Almeida-Silva, U. C., Hallak, J. E., Júnior, W. M., & Osório Fde, L. (2013). Association between spinocerebellar ataxias caused by glutamine expansion and psychiatric and neuropsychological signals—A literature review. American Journal of Neurodegenerative Disease, 2(2), 57–69.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Klockgether, T., & Paulson, H. (2011). Milestones in ataxia. Movement Disorders, 26, 1134–1141.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Van de Warrenburg, B. P. C., Steijns, J. A., Munneke, M., Kremer, H. P., & Bloem, B. R. (2005). Falls in degenerative cerebellar ataxias. Movement Disorders, 20, 497–508.PubMedCrossRefGoogle Scholar
  29. 29.
    Fonteyn, E. M., Schmitz-Hübsch, T., Verstappen, C. C., Baliko, L., Bloem, B. R., Boesch, S., et al. (2010). Falls in spinocerebellar ataxias: Results of the EuroSCA fall study. Cerebellum, 9(2), 232–239.PubMedCrossRefGoogle Scholar
  30. 30.
    Hart, P. E., Lodi, R., Rajagopalan, B., Bradley, J. L., Crilley, J. G., Turner, C., et al. (2005). Antioxidant treatment of patients with Friedreich ataxia: Four-year follow-up. Archives of Neurology, 62, 621–626.PubMedCrossRefGoogle Scholar
  31. 31.
    Strupp, M., Teufel, J., Habs, M., Feuerecker, R., Muth, C., van de Warrenburg, B. P., et al. (2013). Effects of acetyl-DL-leucine in patients with cerebellar ataxia: A case series. Journal of Neurology, 260, 2556–2561.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Perroud, B., Jafar-Nejad, P., Wikoff, W. R., Gatchel, J. R., Wang, L., Barupal, D. K., et al. (2013). Pharmacometabolomic signature of ataxia SCA1 mouse model and lithium effects. PLoS One, 8(8), e70610.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Di Prospero, N. A., Baker, A., Jeffries, N., & Fischbeck, K. H. (2007). Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: A randomised, placebo-controlled trial. Lancet Neurology, 6(10), 878–886.CrossRefGoogle Scholar
  34. 34.
    Schöls, L., Bauer, P., Schmidt, T., Schulte, T., & Riess, O. (2004). Autosomal dominant cerebellar ataxias: Clinical features, genetics, and pathogenesis. Lancet Neurology, 3(5), 291–304.CrossRefGoogle Scholar
  35. 35.
    Basu, P., Chattopadhyay, B., Gangopadhaya, P. K., Mukherjee, S. C., Sinha, K. K., Das, S. K., et al. (2000). Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2 and SCA6 loci in nine ethnic populations of eastern India. Human Genetics, 106(6), 597–604.PubMedCrossRefGoogle Scholar
  36. 36.
    Hernandez-Castillo, C. R., Alcauter, S., Galvez, V., Barrios, F. A., Yescas, P., Ochoa, A., et al. (2013). Disruption of visual and motor connectivity in spinocerebellar ataxia type 7. Movement Disorders, 28, 1708–1716.PubMedCrossRefGoogle Scholar
  37. 37.
    Lebre, A. S., & Brice, A. (2003). Spinocerebellar ataxia 7 (SCA7). Cytogenetic and Genome Research, 100(1–4), 154–163.PubMedCrossRefGoogle Scholar
  38. 38.
    Delatycki, M. B., Williamson, R., & Forrest, S. M. (2000). Friedreich ataxia: An overview. Journal of Medical Genetics, 37, 1–8.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Campuzano, V., Montermini, L., Molto, M. D., Pianese, L., Cossee, M., Cavalcanti, F., et al. (1996). Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science, 271(5254), 1423–1427.PubMedCrossRefGoogle Scholar
  40. 40.
    Cossee, M., Durr, A., Schmitt, M., Dahl, N., Trouillas, P., Allinson, P., et al. (1999). Friedreich’s ataxia: Point mutations and clinical presentation of compound heterozygotes. Annals of Neurology, 45(2), 200–206.PubMedCrossRefGoogle Scholar
  41. 41.
    Lodi, R., Cooper, J. M., Bradley, J. L., Manners, D., Styles, P., Taylor, D. J., et al. (1999). Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proceedings of the National Academy of Sciences of the United States of America, 96, 11492–11495.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    McKinnon, W. C., Baty, B. J., Bennett, R. L., Magee, M., Neufeld-Kaiser, W. A., Peters, K. F., et al. (1997). Predisposition genetic testing for late-onset disorders in adults. A position paper of the National Society of Genetic Counselors. The Journal of the American Medical Association, 278(15), 1217–1220.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Neurology, Center for Patient Care and Outcomes Research (PCOR)Medical College of WisconsinMilwaukeeUSA
  2. 2.Taub InstituteColumbia University Medical CenterNew YorkUSA

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