Teacher: Dr. Devin Parry
The familial nature of genetic information causes an ethical dilemma regarding the disclosure of such knowledge to biological relatives when a family member is diagnosed with a hereditary disease. One typical example is Huntington’s disease (HD), an autosomal dominant neurodegenerative disorder caused by expansion of the CAG trinucleotide in the huntingtin (HTT) gene(1,2). The mutant HTT gene encodes an abnormal protein which causes the disruption and eventual death of neurons in the brain, leading to movement disorders, psychiatric disturbances, and early death(1). The patient’s decision regarding disclosure may have profound implications for other family members and future generations. Here, I present opposing arguments as to whether the father, Jonathan, should disclose the diagnosis of HD to his daughter, Sarah.
For Jonathan, the diagnosis of HD is undoubtedly devastating. As a father, Jonathan may immediately feel a sense of duty to protect Sarah’s right to enjoy her life in “blissful ignorance,” knowing the lack of effective therapy. It is well-documented that predictive genetic testing can cause emotional distress(3). As a patient, Jonathon’s right to privacy regarding his medical information(4) allows him to decide to what extent he would like his family informed. By withholding the information, he realizes his goal to prevent emotional distress among loved ones resulting from knowledge of the dreadful diagnosis.
Sometimes ignorance is preferable to the burden of knowledge, especially in the case of incurable genetic diseases. As someone potentially at risk for HD, Sarah has a right to not know her genetic status and live unencumbered by undesired knowledge. This right is recognized by major international conventions such as UNESCO(5).
As Jonathon’s genetic counselor, Karen has the duty to honor the patient’s right to privacy. According to American Medical Association guidelines, physicians are obliged to hold patient’s medical information strictly confidential, unless consented by the patient or required by law.
Because of the autosomal dominant inheritance of HD, Sarah has a 50% chance of inheriting the mutation that is almost fully penetrant(1,2). Therefore, it can be argued that Jonathan has the duty to share the information, as it may be of enormous importance for Sarah in deciding major life events in the future. For instance, if Sarah chooses to have children, it would allow her to ensure their health and safety by performing prenatal testing or preimplantation genetic diagnosis. By informing Sarah, Jonathan would accomplish his goal to protect her long-term interests.
Sarah’s risk of disease onset could potentially be as soon as within a few years, depending on a number of factors, particularly the size of the CAG repeat expansion in the mutant allele(6). Sarah has the right to decide whether to pursue genetic testing so that she can make decisions about her future accordingly. However, she can only exercise her autonomy to make such choices if she is informed. Disclosing the information to Sarah would also allow her to better support her father throughout his disease process, which will be especially important due to HD patients’ higher risk of developing severe psychiatric issues(2).
Karen, as a genetic counselor, has a goal to prevent unnecessary harm. While she is bound by provider-patient confidentiality, she has a duty to educate Jonathon about the reason for disclosure, develop strategies to help overcome communication issues, and encourage him to disclose.
Defense for Disclosure
Research shows that a common motivation behind nondisclosure to family members is to prevent emotional suffering and avoid receiving blame(7). This is especially true for patients with HD, for which there has been no curative but rather only symptomatic treatment thus far. However, with the landscape of treatment for HD rapidly changing, the balance between harm and benefit associated with disclosure is also evolving. Several new advances have offered bright hope in the world of HD. For example, a drug in late-stage clinical development called RG6042 has shown the most promise(8), achieving up to 60% decrease of mutant huntingtin protein(8,9). Many others are also encouraging, such as precision targeting of the mutant HTT, RNA interference (AMT-130), VX15 antibody, and novel small molecule (Risdplam)(9,10) . Additionally, the advent of CRISPR gene editing technology offers possibility to permanently inactivate the mutant HTT gene(9-11).
The promising new treatments that may soon become available for HD would greatly help Jonathan to overcome major barriers in disclosing the familial genetic information. Moreover, the accessibility to disease-modifying therapeutics would vastly increase Sarah’s potential benefit from early diagnosis and intervention. Thus, the balance of benefit vs. risk has increasingly shifted in favor of disclosure.
1. McColgan, P., Tabrizi, S. J. (2018). Huntington's disease: a clinical review. European Journal of Neurology, 25(1), 24-34.
2. Ghosh, R., Tabrizi. S. J. (2018). Clinical Features of Huntington's Disease. Advances in Experimental Medicine and Biology, 1049,1-28. doi: 10.1007/978-3-319-71779-1
3. Codori, A. M., Brandt, J. (1994). Psychological costs and benefits of predictive testing for Huntington's disease. American Journal of Medical Genetics, 54(3), 174-84.
4. Health Insurance Portability and Accountability Act of 1996, Public Law 104-191.
5. Andorno, R. (2004). The right not to know: an autonomy based approach. Journal of Medical Ethics, 35(4), 435-440.
6. Ahmad Aziz, N., van der Burg, J. M. M., Tabrizi, S. J., Bernhard Landwehrmeyer, G. (2018). Overlap between age-at-onset and disease-progression determinants in Huntington disease. Neurology, 90(24): e2099–e2106. doi: 10.1212/WNL.0000000000005690
7. Vavolizza, R. D., Kalia, I., Aaron, K. E., Silverstein, L. B., Barlevy, D., Wasserman, D., Walsh, C., Marion, R. W., and Dolan, S. M. (2015). Disclosing Genetic Information to Family Members about Inherited Cardiac Arrhythmias: An Obligation or a Choice? Journal of Genetic Counseling, 24 (4), 608–615.
8. Wild, E. J,, Tabrizi, S. J. (2017). Therapies targeting DNA and RNA in Huntington's disease. Lancet Neurolology, 16(10), 837-847. doi: 10.1016/S1474-4422(17)30280-6.
9. Liam, D. (2018). The big hope for Huntington’s. Nature, 557, S39-S41.
10. Kieburtz, K., Reilmann, R., Olanow, C. W. (2018). Huntington's disease: Current and future therapeutic prospects. Movement Disorders, 33(7), 1033-1041. doi: 10.1002/mds.27363. Epub 2018 May 8.
11. Eisensten, M. (2018). To cut is to cure. Nature, 557, S42-S43.