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“Grasping the Grey”: Patient Understanding and Interpretation of an Intermediate Allele Predictive Test Result for Huntington Disease

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Journal of Genetic Counseling

Abstract

Since the discovery of the genetic mutation underlying Huntington disease (HD) and the development of predictive testing, the genetics of HD has generally been described as straightforward; an individual receives either mutation-positive or negative predictive test results. However, in actuality, the genetics of HD is complex and a small proportion of individuals receive an unusual predictive test result called an intermediate allele (IA). Unlike mutation-positive or negative results, IAs confer uncertain clinical implications. While individuals with an IA will usually not develop HD, there remains an unknown risk for their children and future generations to develop the disorder. The purpose of this study was to explore how individuals understood and interpreted their IA result. Interviews were conducted with 29 individuals who received an IA result and 8 medical genetics service providers. Interviews were analyzed using the constant comparative method and the coding procedures of grounded theory. Many participants had difficulty “Grasping the Grey” (i.e. understanding and interpreting their IA results) and their family experience, beliefs, expectations, and genetic counseling influenced the degree of this struggle. The theoretical model developed informs clinical practice regarding IAs, ensuring that this unique subset of patients received appropriate education, support, and counseling.

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Acknowledgements

We would like to thank the study participants and medical genetics service providers who shared their time and experiences with us. Funding for this study has been provided by the Canadian Institutes of Health Research. Alicia Semaka is funded by a Senior Trainee Award from the Michael Smith Foundation for Health Research and a Doctoral Award from the Canadian Institutes of Health Research. Lynda Balneaves holds a New Investigator Award from the Canadian Institutes of Health Research. Michael Hayden is a Killam University Professor and holds a Canada Research Chair in Human Genetics and Molecular Medicine.

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Authors and Affiliations

  1. Department of Medical Genetics, Centre for Molecular Medicine & Therapeutics, University of British Columbia, 950 West 28th Ave, Vancouver, BC, V5Z 4H4, Canada

    A. Semaka & M. R. Hayden

  2. School of Nursing, University of British Columbia, Vancouver, BC, Canada

    L. G. Balneaves

Authors
  1. A. Semaka
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  2. L. G. Balneaves
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  3. M. R. Hayden
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Corresponding author

Correspondence to A. Semaka.

Appendix I: Sample Questions from Participant Interview Guides

Appendix I: Sample Questions from Participant Interview Guides

Interview Guide #1

  • How did you come to pursue predictive (genetic) testing for Huntington disease (HD)?

    • What was going on in your life prior to deciding to undergo predictive testing?

  • What, if anything, did you know about the possible predictive test results you could receive through predictive testing (i.e. prior to actually receiving your result)?

  • What do you recall being told about your predictive-test result?

    • What was your result called?

    • What does your result mean for your risk to develop HD? What does it mean for your children’s risk to develop HD?

  • How do you feel you understand the implications of your predictive-test result for yourself, your children, and your extended family members?

    • What do you understand? What do you not understand?

    • Do you think your understanding could be improved? How?

  • How did you feel about your predictive-test result initially?

    • How do you feel about your result now?

    • Why do you feel this way?

  • How has your predictive-test result influenced your life, if at all?

    • Has your result influenced your family relationships? Your plans for career or family?

    • What have you done, or not done, because of your result?

    • How has your life changed since receiving your result? Do you consider these positive or negative changes?

  • Who has been the most helpful to you during your predictive testing? How have they been helpful?

  • Do you have any recommendations on how the predictive testing process could be improved for others receiving a predictive test result like your own?

Interview Guide #2:

  • Can you tell me about your family experience with HD?

    • How old were you when you first found out about HD in your family?

    • How does HD typically appear in your family (symptoms, age of onset)?

    • What is your understanding of how HD is inherited in your family?

    • Is there anything special or unusual about the HD in your family?

  • How do you feel about having HD in your family?

    • How do you view the seriousness of HD?

    • How do you feel when you see your affected family members?

  • Ask the following questions if applicable to participant’s family history (i.e. long-standing family history of HD with multiple affected family members)…

    • How do you think your experience would differ if the first person in your family to have HD was your sibling, instead of your parent and grandparent? Why do you think this would/would not change your experience?

  • Ask the following questions if applicable to participant’s family history (i.e. new mutation family history, sporadic diagnosis of HD in sibling or parent)…

    • How was your sibling/parent diagnosed with HD? What was this experience like for you and your family? Had you heard of HD before?

    • What was your reaction to the HD diagnosis? How did you feel about it?

    • How do you think your experience would differ if you had a long-standing family history of HD with multiple affected family members? Why do you think this would/would not change your experience?

  • What is your understanding of the cause of HD?

    • What do you understand about the genetics of HD?

    • What is your understanding of how HD is passed down in families? Do you have to have a family history of HD to develop the disease? Why or why not?

    • Where did you learn about the (genetic) causes of HD?

  • How did you learned of your own risk to develop HD? From whom did you learn of your risk? When?

    • What was your reaction to learning that you were at-risk? How did you feel about your risk?

    • Prior to going for predictive testing, what did you believe your risk to be? How serious of a risk did you feel it was? Why?

  • What, if anything, did you know about the possible predictive-test results you could receive through predictive testing (i.e. prior to actually receiving your result)?

    • What information did you think you would learn about your own risk to develop HD? Your children’s risk?

  • What do you recall being told about your predictive-test result?

    • What was your result called?

    • What does your result mean for your risk to develop HD? Your children’s risk to develop HD?

    • Can you tell me how your result relates to your family history of HD? Who did you inherit your result from, your mom or your dad?

  • Ask the following question if applicable to participant’s understanding (i.e. understands a risk remains for their children to develop HD, even though they will not develop HD)…

    • Can you explain to me how it is possible for your children to develop HD but you will not?

  • How do you feel about your results?

    • How do you feel about the meaning of your result for your risk to develop HD? Your children’s risk to develop HD?

    • How, if at all, has your result changed your feelings about HD?

  • Ask the following question if applicable to participant’s understanding (i.e. understands a risk remains for their children to develop HD, even though they will not develop HD)…

    • When you think of your children’s risk to develop HD, what do you think of?

    • Do you think your family history has influenced how you view your children’s risk? How? Why?

    • How do you view the seriousness of the risk to your children? Why?

  • What was your reaction to your predictive test result?

    • How did you feel when you heard your results?

    • What was your reaction to the meaning of your result for your risk to develop HD? Your children’s risk?

    • What do you think influenced the way you reacted to your result (i.e. your family history, the genetic counselling you received)?

  • How do you feel you understand the implications of your predictive-test result for yourself, your children, and your extended family members?

    • What do you understand? What do you not understand?

    • What has influenced your understanding (i.e. your family history, the genetic counselling you received)?

    • Do you think your understanding could be improved? How?

  • How has your predictive-test result influenced your life, if at all?

    • Has your result influenced your family relationships? Your plans for career or family?

    • What have you done, or not done, because of your result?

    • How has your life changed since receiving your result? Do you consider these positive or negative changes?

  • How do you feel about your predictive testing experience?

    • Do you feel predictive testing met your needs? Why or why not?

    • Do you have any recommendations on how the predictive testing process could be improved for others receiving a predictive test result like the one you received?

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Semaka, A., Balneaves, L.G. & Hayden, M.R. “Grasping the Grey”: Patient Understanding and Interpretation of an Intermediate Allele Predictive Test Result for Huntington Disease. J Genet Counsel 22, 200–217 (2013). https://doi.org/10.1007/s10897-012-9533-7

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