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Journal of Genetic Counseling

, Volume 23, Issue 5, pp 725–733 | Cite as

Amyotrophic Lateral Sclerosis in a Patient with a Family History of Huntington Disease: Genetic Counseling Challenges

  • Andrea L. SmithEmail author
  • James W. Teener
  • Brian C. Callaghan
  • Jack Harrington
  • Wendy R. Uhlmann
Case Presentation

Abstract

Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are generally considered to be distinct and easily differentiated neurologic conditions. However, there are case reports of the co-occurrence of ALS with HD. We present a 57-year-old male with a clinical diagnosis of sporadic ALS in the context of a family history of HD. This case adds to the limited literature regarding individuals with a family history of HD who present with features of ALS. There were several genetic counseling challenges in counseling this patient including the diagnostic consideration of two fatal conditions, complex risk information, the personal and familial implications, and the patient’s inability to communicate verbally or through writing due to disease progression. DNA banking effectively preserved the right of our patient and his wife not to learn his HD genetic status during a stressful time of disease progression while providing the option for family members to learn this information in the future if desired. We present lessons learned and considerations for other clinical genetics professionals who are presented with similar challenging issues.

Keywords

Amyotrophic lateral sclerosis (ALS) Huntington disease (HD) Genetic counseling 

Notes

Acknowledgments

The authors gratefully acknowledge our patient and his wife.

Conflict of Interest

Andrea L. Smith, James W. Teener, Brian C. Callaghan, Jack Harrington, and Wendy R. Uhlmann declare that they have no conflicts of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

References

  1. Armon, C., Kurland, L. T., Daube, J. R., & O’Brien, P. C. (1991). Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology, 41(7), 1077–1084.PubMedGoogle Scholar
  2. Ball, L., Beukelman, D., & Pattee, G. (2004). Augmentative and alternative communication acceptance by persons with amyotrophic lateral sclerosis. Augmentative and Alternative Communication, 20, 113–123.Google Scholar
  3. Bates, G., Harper, P., & Jones, L. (2002). Huntington’s disease. New York: Oxford University Press.Google Scholar
  4. Blin, O., Samuel, D., Guieu, R., Pouget, J., Nieoullon, A., & Serratrice, G. (1992). Familial amyotrophic lateral sclerosis associated with Huntington chorea with increased aspartate level in the cerebrospinal fluid. Revue Neurologique (Paris), 148(2), 144–146.Google Scholar
  5. Bloch, M., Fahy, M., Fox, S., & Hayden, M. R. (1989). Predictive testing for Huntington disease: II. Demographic characteristics, life-style patterns, attitudes, and psychosocial assessments of the first 51 test candidates. American Journal of Medical Genetics, 32, 217–224.PubMedGoogle Scholar
  6. Brooks, B. R. (1994). El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. Journal of Neurological Sciences, 124(Suppl), 96–107.Google Scholar
  7. Chettri, S.K., Dayanandan, R., Bindman, D., Crauford, D., Majeed, T. (2013). Amyotrophic lateral sclerosis and Huntington’s disease: Neurodegenerative link or coincidence? Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print: Pages 1–3.Google Scholar
  8. Craufurd, D., Dodge, A., Kerzin-Storrar, L., & Harris, R. (1989). Uptake of presymptomatic predictive testing for Huntington’s disease. Lancet, 2(8663), 603–605.PubMedGoogle Scholar
  9. DeJesus-Hernandez, M., Mackenzie, I. R., et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron, 72(2), 245–256.PubMedPubMedCentralGoogle Scholar
  10. Deng, H. X., Chen, W., et al. (2011). Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature, 477(7363), 211–215.PubMedPubMedCentralGoogle Scholar
  11. Dufrasne, S., Roy, M., Galvez, M., & Rosenblatt, D. S. (2011). Experience over 15 years with a protocol for predictive testing for Huntington’s disease. Molecular Genetics and Metabolism, 102, 494–504.Google Scholar
  12. Evers-Kiebooms, G., Swerts, A., Cassiman, J. J., & Van Den Berghe, H. (1989). The motivation of at-risk individuals and their partners in deciding for or against predictive testing for Huntington’s disease. Clinical Genetics, 35, 29–40.PubMedGoogle Scholar
  13. Evers-Kiebooms, G., Nys, K., Harper, P., Zoeteweij, M., Durr, A., Jacopini, G., et al. (2002). Predictive DNA testing for Huntington’s disease and reproductive decision making: a European collaborative study. European Journal of Human Genetics, 10, 167–176.PubMedGoogle Scholar
  14. Forrest Keenan, K., van Teijlingen, E., McKee, L., Miedzybrodzka, Z., & Simpson, S. A. (2009). How young people find out about their family history of Huntington’s disease. Social Science & Medicine, 68, 1892–1900.Google Scholar
  15. Forrest, K., Simpson, S. A., Wilson, B. J., van Teijlingen, E. R., McKee, L., Haites, N., et al. (2003). Clinical Genetics, 64, 317–326.PubMedPubMedCentralGoogle Scholar
  16. Frank, G., & Vuia, O. (1973). Huntington’s chorea–amyotrophic lateral sclerosis-spastic spinal paralysis. Association of systemic diseases (author’s transl). Zeitschrift für Neurologie, 205(3), 207–220.PubMedGoogle Scholar
  17. Gasbarrini, A., ed. (1964). Amyotrophische Lateralsklerose. Stuttgart: Fischer. WF H, ed.Google Scholar
  18. Greenway, M. J., Andersen, P. M., et al. (2006). ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis. Nature Genetics, 38(4), 411–413.PubMedGoogle Scholar
  19. Guimaraes, L., Sequeiros, J., Skirton, H., & Paneque, M. (2013). What counts as effective genetic counselling for presymptomatic testing in late-onset disorders? a study of the Consultand’s perspective. Journal of Genetic Counseling, 22(4), 437–447.PubMedGoogle Scholar
  20. Harper, P. S., & Newcombe, R. G. (1992). Age at onset and life table risks in genetic counselling for Huntington’s disease. Journal of Medical Genetics, 29, 239–242.PubMedPubMedCentralGoogle Scholar
  21. Holt, K. (2006). What do we tell the children? Contrasting the choices of two HD families regarding risk status and predictive genetic testing. Journal of Genetic Counseling, 15(4), 253–265.PubMedPubMedCentralGoogle Scholar
  22. 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.Google Scholar
  23. 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.PubMedGoogle Scholar
  24. Kanai, K., Kuwabara, S., Sawai, S., et al. (2008). Genetically confirmed Huntington’s disease masquerading as motor neuron disease. Movement Disorders, 23(5), 748–751.PubMedGoogle Scholar
  25. Klitzman, R., Thorne, D., Williamson, J., Chung, W., & Marder, K. (2007). Decision-making about reproductive choices among individuals at-risk for Huntington’s disease. Journal of Genetic Counseling, 16(3), 347–362.PubMedPubMedCentralGoogle Scholar
  26. Kondo, K., & Tsubaki, T. (1981). Case-control studies of motor neuron disease: association with mechanical injuries. Archives of Neurology, 38(4), 220–226.PubMedGoogle Scholar
  27. Kwiatkowski, T. J., Jr., Bosco, D. A., et al. (2009). Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 323(5918), 1205–1208.PubMedGoogle Scholar
  28. MacLeod, R., Tibben, A., Frontali, M., et al. (2013). Recommendations for the predictive genetic test in Huntington’s disease. Clinical Genetics, 83(3), 221–231.PubMedGoogle Scholar
  29. Mandrioli, J., Bernabei, C., Georgoulopoulou, E., Nichelli, P., Cortelli, P., Tupler, R., et al. (2010). Comment on Huntington’s disease presenting as ALS. Amyotrophic Lateral Sclerosis, 11, 408–409.PubMedGoogle Scholar
  30. Maruyama, H., Morino, H., et al. (2010). Mutations of optineurin in amyotrophic lateral sclerosis. Nature, 465(7295), 223–226.PubMedGoogle Scholar
  31. Mizutani, T., Aki, M., Shiozawa, R., Unakami, M., Nozawa, T., Yajima, K., et al. (1990). Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators. Journal of Neurological Sciences, 99(2–3), 311–319.Google Scholar
  32. Myers, R. H., Sax, D. S., Schoenfeld, M., et al. (1985). Late onset of Huntington’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 48(6), 530–534.PubMedGoogle Scholar
  33. Nagaraja, S. M., Jain, S., & Muthane, U. B. (2006). Perspectives towards predictive testing in Huntington disease. Neurology India, 54, 359–362.PubMedGoogle Scholar
  34. National Society of Genetic Counselors. (2013). DNA Banking. https://doi.org/www.nsgc.org/DNABanking/tabid/156/Default.aspx.
  35. Panse, F., ed. (1942). Die Erbchorea. Leipzig. G. Theime, ed. Eine-klinisch-genetische Studie.Google Scholar
  36. Papageorgiou, S. G., Antell, A., Bonakis, A., et al. (2006). Association of genetically proven Huntington’s disease and sporadic amyotrophic lateral sclerosis in a 72-year-old woman. Journal of Neurology, 253(12), 1649–1650.PubMedGoogle Scholar
  37. Phukan, J., Ali, E., Pende, N. P., et al. (2010). Huntington’s disease presenting as amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 11(4), 405–407.PubMedGoogle Scholar
  38. Pringsheim, T., Wiltshire, K., Day, L., Dykeman, J., Steeves, T., & Jette, N. (2012). The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Movement Disorders, 27(9), 1083–1091.Google Scholar
  39. Quaid, K. A., & Morris, M. (1993). Reluctance to undergo predictive testing: the case of Huntington disease. American Journal of Medical Genetics, 45(1), 41–45.PubMedPubMedCentralGoogle Scholar
  40. Quaid, K. A., Swenson, M. M., Sims, S. L., Harrison, J. M., Moskowitz, C., Stepanov, N., et al. (2010). What were you thinking?: Individuals at risk for Huntington disease talk about having children. Journal of Genetic Counseling, 19, 606–617.PubMedPubMedCentralGoogle Scholar
  41. Renton, A. E., Majounie, E., et al. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72(2), 257–268.PubMedPubMedCentralGoogle Scholar
  42. Roos, R. A. (2010). Huntington’s disease: a clinical review. Orphanet Journal of Rare Diseases, 5(1), 40.PubMedPubMedCentralGoogle Scholar
  43. Rubio, K. S., Figlewicz, D. A., Greenamyre, T., Shoulson, I., Hamill, R., & Powers, J. (1995). Amyotrophy and Huntington’s disease. Journal of Neuropathology and Experimental Neurology, 54(3), 443.Google Scholar
  44. Rubio, A., Steinberg, K., Figlewicz, D. A., et al. (1996). Coexistence of Huntington’s disease and familial amyotrophic lateral sclerosis: case presentation. Acta Neuropathologica, 92(4), 421–427.PubMedGoogle Scholar
  45. Sadeghian, H., O’Suilleabhain, P. E., Battiste, J., Elliott, J. L., & Trivedi, J. R. (2011). Huntington chorea presenting with motor neuron disease. Archives of Neurology, 68(5), 650–652.PubMedGoogle Scholar
  46. Savettieri, G., Salemi, G., Arcara, A., Cassata, M., Castiglione, M. G., & Fierro, B. (1991). A case-control study of amyotrophic lateral sclerosis. Neuroepidemiology, 10(5–6), 242–245.PubMedGoogle Scholar
  47. Shaw, C. E., Enayat, Z. E., et al. (1998). Mutations in all five exons of SOD-1 may cause ALS. Annals of Neurology, 43(3), 390–394.PubMedGoogle Scholar
  48. Skirton, H., Goldsmith, L., Jackson, L., & Tibben, A. (2013). Quality in genetic counselling for presymptomatic testing - clinical guidelines for practice across the range of genetic conditions. European Journal of Human Genetics, 21(3), 256–260.PubMedGoogle Scholar
  49. Smith, J. A., Stephenson, M., Jacobs C., & Quarrell, O. (2013). Doing the right thing for one’s children: deciding whether to take the genetic test for Huntington’s disease as a moral dilemma. Clinical Genetics, 83, 417–421.PubMedGoogle Scholar
  50. Sreedharan, J., Blair, I. P., et al. (2008). TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science, 319(5870), 1668–1672.PubMedGoogle Scholar
  51. Tada, M., Coon, E. A., Osmand, A. P., et al. (2012). Coexistence of Huntington’s disease and amyotrophic lateral sclerosis: a clinicopathologic study. Acta Neuropathologica, 124(5), 749–760.PubMedPubMedCentralGoogle Scholar
  52. Testa, D., Lovati, R., Ferrarini, M., Salmoiraghi, F., & Filippini, G. (2004). Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 5(4), 208–212.PubMedGoogle Scholar
  53. The 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(6), 971–983.Google Scholar
  54. Traynor, B. J., Codd, M. B., Corr, B., Forde, C., Frost, E., & Hardiman, O. (1999). Incidence and prevalence of ALS in Ireland, 1995–1997: a population-based study. Neurology, 52(3), 504–509.PubMedGoogle Scholar
  55. Uhlmann, W., Schuette, J., & Yashar, B. (Eds.). (2009). A guide to genetic counseling (2nd ed.). Hoboken: John Wiley & Sons.Google Scholar
  56. Walker, F. O. (2007). Huntington’s disease. Lancet, 369(9557), 218–228.PubMedGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2014

Authors and Affiliations

  • Andrea L. Smith
    • 1
    Email author
  • James W. Teener
    • 2
  • Brian C. Callaghan
    • 2
  • Jack Harrington
    • 3
  • Wendy R. Uhlmann
    • 4
  1. 1.Department of NeurologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of NeurologyUniversity of Michigan Medical SchoolAnn ArborUSA
  3. 3.Department of Social WorkUniversity of Michigan Health SystemAnn ArborUSA
  4. 4.Departments of Internal Medicine and Human GeneticsUniversity of Michigan Medical SchoolAnn ArborUSA

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