Skip to main content

Amyotrophic Lateral Sclerosis

  • 1285 Accesses

Abstract

Amyotrophic lateral sclerosis (ALS) is a usually rapidly progressive neurodegenerative disease characterized by involvement of both the upper and lower motor neurons. Approximately 5–10% of ALS is hereditary and caused by both autosomal dominant and autosomal recessive genes. Gene mutations have been discovered in apparently sporadic cases. Genetic counseling for ALS should include the overlap between ALS and other conditions including FTD, which should be carefully screened while taking the family history. Because of the complexity of ALS genetics, a mutation should be confirmed in an affected individual before predictive testing. These issues are discussed in this chapter.

Keywords

  • Amyotrophic Lateral Sclerosis
  • Genetic Counselor
  • Spinal Muscular Atrophy
  • Lower Motor Neuron
  • Sporadic Amyotrophic Lateral Sclerosis

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.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4899-7482-2_13
  • Chapter length: 20 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   59.99
Price excludes VAT (USA)
  • ISBN: 978-1-4899-7482-2
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   74.99
Price excludes VAT (USA)
Hardcover Book
USD   109.99
Price excludes VAT (USA)
Fig. 13.1

References

  1. Wijesekera, L. C., & Leigh, P. N. (2009). Amyotrophic lateral sclerosis. Orphanet Journal of Rare Diseases, 4, 3.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  2. Logroscino, G., Beghi, E., Zoccolella, S., Palagano, R., Fraddosio, A., Simone, I. L., et al. (2005). Incidence of amyotrophic lateral sclerosis in southern Italy: A population based study. Journal of Neurology, Neurosurgery, and Psychiatry, 76(8), 1094–1098.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  3. Juneja, T., Pericak-Vance, M. A., Laing, N. G., Dave, S., & Siddique, T. (1997). Prognosis in familial amyotrophic lateral sclerosis: Progression and survival in patients with glu100gly and ala4val mutations in Cu, Zn superoxide dismutase. Neurology, 48(1), 55–57.

    PubMed  CrossRef  Google Scholar 

  4. Andersen, P. M., & Al-Chalabi, A. (2011). Clinical genetics of amyotrophic lateral sclerosis: What do we really know? Nature Reviews Neurology, 7(11), 603–615.

    PubMed  CrossRef  Google Scholar 

  5. Zoccolella, S., Beghi, E., Palagano, G., Fraddosio, A., Guerra, V., Samarelli, V., et al. (2008). Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: A population based study. Journal of Neurology, Neurosurgery, and Psychiatry, 79(1), 33–37.

    PubMed  CrossRef  Google Scholar 

  6. Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., et al. (1998). Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology, 51(6), 1546–1554.

    PubMed  CrossRef  Google Scholar 

  7. Portet, F., Cadilhac, C., Touchon, J., & Camu, W. (2001). Cognitive impairment in motor neuron disease with bulbar onset. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 2(1), 23–29.

    PubMed  CrossRef  Google Scholar 

  8. Lomen-Hoerth, C., Murphy, J., Langmore, S., Kramer, J. H., Olney, R. K., & Miller, B. (2003). Are amyotrophic lateral sclerosis patients cognitively normal? Neurology, 60(7), 1094–1097.

    PubMed  CrossRef  Google Scholar 

  9. Traynor, B. J., Codd, M. B., Corr, B., Forde, C., Frost, E., & Hardiman, O. M. (2000). Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Archives of Neurology, 57(8), 1171–1176.

    PubMed  CrossRef  Google Scholar 

  10. Millul, A., Beghi, E., Logroscino, G., Micheli, A., Vitelli, E., & Zardi, A. (2005). Survival of patients with amyotrophic lateral sclerosis in a population-based registry. Neuroepidemiology, 25(3), 114–119.

    PubMed  CrossRef  Google Scholar 

  11. Brooks, B. R., Miller, R. G., Swash, M., Munsat, T. L., & World Federation of Neurology Research Group on Motor Neuron Diseases. (2000). El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 1(5), 293–299.

    PubMed  CrossRef  Google Scholar 

  12. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., et al. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314(5796), 130–133.

    PubMed  CrossRef  Google Scholar 

  13. Al-Chalabi, A., Jones, A., Troakes, C., King, A., Al-Sarraj, S., & van den Berg, L. H. (2012). The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuropathologica, 124(3), 339–352.

    PubMed  CrossRef  Google Scholar 

  14. DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., et al. (2012). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron, 72(2), 245–256.

    CrossRef  Google Scholar 

  15. Renton, A. E., Majounie, E., Waite, A., Simon-Sanchez, J., Rollinson, S., Gibbs, J. R., et al. (2012). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72(2), 257–268.

    CrossRef  Google Scholar 

  16. Andersen, P. M., Borasio, G. D., Dengler, R., Hardiman, O., Kollewe, K., Leigh, P. N., et al. (2005). EFNS task force on management of amyotrophic lateral sclerosis: Guidelines for diagnosing and clinical care of patients and relatives. European Journal of Neurology, 12(12), 921–938.

    PubMed  CrossRef  Google Scholar 

  17. Turner, M. R., Hardiman, O., Benatar, M., Brooks, B. R., Chio, A., de Carvalho, M., et al. (2013). Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurology, 12(3), 310–322.

    CrossRef  Google Scholar 

  18. Radunovic, A., Mitsumoto, H., & Leigh, P. N. (2007). Clinical care of patients with amyotrophic lateral sclerosis. Lancet Neurology, 6(10), 913–925.

    CrossRef  Google Scholar 

  19. Byrne, S., Walsh, C., Lynch, C., Bede, P., Elamin, M., Kenna, K., et al. (2011). Rate of familial amyotrophic lateral sclerosis: A systematic review and meta-analysis. Journal of Neurology, Neurosurgery, and Psychiatry, 82(6), 623–627.

    PubMed  CrossRef  Google Scholar 

  20. Byrne, S., Bede, P., Elamin, M., Kenna, K., Lynch, C., McLaughlin, R., et al. (2011). Proposed criteria for familial amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 12(3), 157–159.

    PubMed  CrossRef  Google Scholar 

  21. Conte, A., Lattante, S., Luigetti, M., Del Grande, A., Romano, A., Marcaccio, A., et al. (2012). Classification of familial amyotrophic lateral sclerosis by family history: Effects on frequency of genes mutation. Journal of Neurology, Neurosurgery, and Psychiatry, 83(12), 1201–1203.

    PubMed  CrossRef  Google Scholar 

  22. Yang, Y., Hentati, A., Deng, H. X., Dabbagh, O., Sasaki, T., Hirano, M., et al. (2001). The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nature Genetics, 29(2), 160–165.

    PubMed  CrossRef  Google Scholar 

  23. Hadano, S., Hand, C. K., Osuga, H., Yanagisawa, Y., Otomo, A., Devon, R. S., et al. (2001). A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nature Genetics, 29(2), 166–173.

    PubMed  CrossRef  Google Scholar 

  24. Lesca, G., Eymard-Pierre, E., Santorelli, F. M., Cusmai, R., Di Capua, M., Valente, E. M., et al. (2003). Infantile ascending hereditary spastic paralysis (IAHSP): Clinical features in 11 families. Neurology, 60(4), 674–682.

    PubMed  CrossRef  Google Scholar 

  25. Ben Hamida, M., Hentati, F., & Ben, H. C. (1990). Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). Conditions combining a bilateral pyramidal syndrome with limb and bulbar amyotrophy. Brain, 113(Pt 2), 347–363.

    PubMed  CrossRef  Google Scholar 

  26. Rabin, B. A., Griffin, J. W., Crain, B. J., Scavina, M., Chance, P. F., & Cornblath, D. R. (1999). Autosomal dominant juvenile amyotrophic lateral sclerosis. Brain, 122(Pt 8), 1539–1550.

    PubMed  CrossRef  Google Scholar 

  27. Al-Saif, A., Al-Mohanna, F., & Bohlega, S. (2011). A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Annals of Neurology, 70(6), 913–919.

    PubMed  CrossRef  Google Scholar 

  28. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 362(6415), 59–62. Erratum in: Nature, 1993, 364(6435), 362.

    PubMed  CrossRef  Google Scholar 

  29. Redler, R. L., & Dokholyan, N. V. (2012). The complex molecular biology of amyotrophic lateral sclerosis (ALS). Progress in Molecular Biology and Translational Science, 107, 215–262.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  30. Sabatelli, M., Conte, A., & Zollino, M. (2013). Clinical genetic heterogeneity of amyotrophic lateral sclerosis. Clinical Genetics, 83(5), 408–416.

    PubMed  CrossRef  Google Scholar 

  31. Chiò, A., Borghero, G., Pugliatti, M., Ticca, A., Calvo, A., Moglia, C., et al. (2011). Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Archives of Neurology, 68(5), 594–598.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  32. Vance, C., Rogelj, B., Hortobagyi, T., De Vos, K. J., Nishimura, A. L., Sreedharan, J., et al. (2009). Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science, 323(5918), 1208–1211.

    PubMed  CrossRef  Google Scholar 

  33. Kwiatkowski, T. J., Jr., Bosco, D. A., Leclerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., et al. (2009). Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 323(5918), 1205–1208.

    PubMed  CrossRef  Google Scholar 

  34. Millecamps, S., Boillée, S., Le Ber, I., Seilhean, D., Teyssou, E., Giraudeau, M., et al. (2012). Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. Journal of Medical Genetics, 49(4), 258–263.

    PubMed  CrossRef  Google Scholar 

  35. van Blitterswijk, M., DeJesus-Hernandez, M., & Rademakers, R. (2012). How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia: Can we learn from other noncoding repeat expansion disorders? Current Opinion in Neurology, 25(6), 689–700.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  36. Gomez-Tortosa, E., Gallego, J., Guerrero-Lopez, R., Marcos, A., Gil-Neciga, E., Sainz, M. J., et al. (2013). C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with Frontotemporal deterioration. Neurology, 80(4), 366–370.

    PubMed  CrossRef  Google Scholar 

  37. Chio, A., Calvo, A., Mazzini, L., Cantello, R., Mora, G., Moglia, C., et al. (2012). Extensive genetics of ALS: A population-based study in Italy. Neurology, 79(19), 1983–1989.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  38. Chio, A., Borghero, G., Restagno, G., Mora, G., Drepper, C., Traynor, B. J., et al. (2012). Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72. Brain, 135(Pt 3), 784–793.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  39. Irwin, D. J., McMillan, C. T., Brettschneider, J., Libon, D. J., Powers, J., Rascovsky, K., et al. (2013). Cognitive decline and reduced survival in C9orf72 expansion frontotemporal degeneration and amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery, & Psychiatry, 84(2), 163–169.

    CrossRef  Google Scholar 

  40. Nishimura, A. L., Mitne-Neto, M., Silva, H. C., Richieri-Costa, A., Middleton, S., Cascio, D., et al. (2004). A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. American Journal of Human Genetics, 75(5), 822–831.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  41. van Es, M. A., Schelhaas, H. J., van Vught, P. W., Ticozzi, N., Andersen, P. M., Groen, E. J., et al. (2011). Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Annals of Neurology, 70(6), 964–973.

    PubMed  CrossRef  Google Scholar 

  42. Chow, C. Y., Landers, J. E., Bergren, S. K., Sapp, P. C., Grant, A. E., Jones, J. M., et al. (2009). Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. American Journal of Human Genetics, 84(1), 85–88.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  43. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., et al. (2010). Mutations of optineurin in amyotrophic lateral sclerosis. Nature, 465(7295), 223–226.

    PubMed  CrossRef  Google Scholar 

  44. Elden, A. C., Kim, H. J., Hart, M. P., Chen-Plotkin, A. S., Johnson, B. S., Fang, X., et al. (2010). Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature, 466(7310), 1069–1075.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  45. Johnson, J. O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V. M., Trojanowski, J. Q., et al. (2010). Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron, 68(5), 857-64. Erratum in. Neuron, 69(2), 397.

    CrossRef  Google Scholar 

  46. Deng, H. X., Chen, W., Hong, S. T., Boycott, K. M., Gorrie, G. H., Siddique, N., et al. (2011). Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature, 477(7363), 211–215.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  47. Wu, C. H., Fallini, C., Ticozzi, N., Keagle, P. J., Sapp, P. C., Piotrowska, K., et al. (2012). Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature, 488(7412), 499–503.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  48. Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., et al. (2010). Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS ONE, 5(3), e9872.

    PubMed Central  PubMed  CrossRef  Google Scholar 

  49. Fong, J. C., Karydas, A. M., & Goldman, J. S. (2012). Genetic counseling for FTD/ALS caused by the C9ORF72 hexanucleotide expansion. Alzheimer’s Research & Therapy, 4(4), 27.

    CrossRef  Google Scholar 

  50. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s Chorea. (1994). Guidelines for the molecular genetics predictive test in Huntington’s disease. Neurology, 44(8), 1533–1536.

    CrossRef  Google Scholar 

  51. Goldman, J. S., Hahn, S. E., Catania, J. W., LaRusse-Eckert, S., Butson, M. B., Rumbaugh, M., et al. (2011). Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, 13(6), 597–605.

    PubMed Central  PubMed  CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elisabeth McCarty Wood .

Editor information

Editors and Affiliations

1 Electronic Supplementary Material

Rights and permissions

Reprints and Permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wood, E.M. (2015). Amyotrophic Lateral Sclerosis. In: Goldman, J. (eds) Genetic Counseling for Adult Neurogenetic Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7482-2_13

Download citation