A 58-year-old woman was admitted to a residential care facility with a three-year history of psychosis and challenging behaviors initially thought to be a primary neuropsychiatric illness. She has limited social supports: Her husband passed away, and she is estranged from her 30-year-old son, extended family, and former friends. The patient has little insight into her medical condition, lacks capacity to make health care decisions, and has no designated substitute decision-maker. Her father died of amyotrophic lateral sclerosis (ALS). Her brother also died of ALS and had symptoms of frontotemporal dementia.
Concerned about this family history and progressive cognitive decline, a neurologist caring for her orders a genetic test that confirms a pathogenic chromosome 9 open reading frame 72 (C9ORF72) G4C2 hexanucleotide repeat expansion. This genetic mutation is associated with familial ALS, frontotemporal dementia, and parkinsonism. In individuals with this mutation, pathological changes are nearly 100 percent penetrant by the age of 80. The expansion is inherited in an autosomal dominant pattern; therefore, a child of an affected individual has a 50 percent chance of inheriting the anomaly and developing the neurological phenotype. The severity and likelihood of the neurological disorders associated with this finding are compelling the neurologist to consider the implications for her son.
Does the neurologist have a duty to disclose this genetic risk information to the patient's son despite the fact that there is currently no treatment for the condition?
THE NEUROETHICISTS RESPOND
Health care providers may be faced with competing legal obligations when navigating this case. While the neurologist is obliged to keep the patient's medical information confidential, there are cases where the courts have found that clinicians have a duty to disclose patients' medical information to third parties.
United States case law tends to support disclosure of genetic risk to relatives, although the mechanism by which to satisfy disclosure duties remains unclear. In cases such as Pate v. Threkel (1995) and Safer v. Estate of Pack (1996), physicians were held to a duty to disclose genetic risk to patients' known but unknowing relatives, despite their obligation to protect patient privacy. Of significance, both of these cases involved hereditary forms of cancer for which early diagnosis and treatment may alter disease course and possibly save lives.
More relevant to this situation is ABC v St George's Healthcare NHS Trust (2015, 2017) in the United Kingdom, which addressed the duty to disclose Huntington disease. Here, the patient's daughter sued her father's physicians for their failure to disclose the genetic risk to her. The claimant's father was diagnosed with the disease when she was pregnant, and she learned about her father's diagnosis following the birth of her daughter. She argued that the defendants' failure to disclose her genetic risk obstructed her opportunity to pursue genetic testing and possibly terminate her pregnancy, thereby causing the wrongful birth of her daughter.
In 2015, the judge ruled against the claimant, but the case will be re-tried in the Court of Appeal. The decision of the Court of Appeal may well set precedent in the UK about the duty to disclose genetic risk information in circumstances where an opportunity to modify disease course does not exist, but where a benefit to future generations may be possible through family planning (procreative beneficence).
Given the ambiguity of legal precedents, the neurologist may seek guidance from the American Society of Human Genetics (ASHG) on disclosure of genetic mutations to family members of affected individuals. The ASHG guidelines state that disclosure should be permissible where attempts to encourage disclosure on the part of the patient have failed; where the harm is highly likely to occur and is serious and foreseeable; where the at-risk relative(s) is identifiable; and where either the disease is preventable/treatable or medically accepted standards indicate that early monitoring will reduce the genetic risk. And it advises that the harm that may result from failure to disclose should outweigh the harm that may result from disclosure.
Our featured case does not fall clearly within the parameters of ASHG guidance. The main source of ambiguity is whether the disease manifestations of the C9ORF72 gene mutation are preventable. Currently, there is no disease-modifying therapy that can prevent the onset of associated neurological phenotypes. Indeed, both ASGH guidance and legal precedents would apply more strongly to cases where there are means to mitigate health risk. It can be argued, however, that disease can be prevented by disclosure, albeit only to future generations, by means of family planning.
The second criterion necessitates weighing two options — disclosure or non-disclosure — that entail risks of harm.
SO WHAT TO DO?
When considering whether the neurologist has a duty to disclose the 58-year-old's diagnosis because of potential risk to her son it is important to recognize that, unlike most other medical information, genetic information is both personal and familial in nature. While neurologists often center their primary focus on the best interests of their patients, this decision will need to consider the welfare of both the patient and her son.
The patient lacks both insight into her diagnosis and the capacity to make autonomous decisions about disclosure of her genetic risk. She also does not have a substitute decision-maker to provide a surrogate account of how her previously competent wishes and enduring values would guide the decision-making process. Despite her impaired decision-making capacity, the principle of respect for persons necessitates that the neurologist honor the patient's interests, even though there is ambiguity as to what these interests are.
Given an inability to consider Lydia's autonomous wishes, the neurologist must turn to the best interest standard and base the analysis on what a reasonable person in the patient's circumstances might choose, given the unique risks and benefits associated with disclosure of her genetic risk information.
An important consideration is that disclosure to her son may violate the patient's privacy and breach the neurologist's duty to protect confidentiality. Even if the son were not told explicitly that his mother has the C9ORF72 mutation, he would likely be able to deduce this from the family history. The neurologist's duty to protect confidential information is a prima facie duty, that is, one that may be overridden by a more compelling interest. In this case, justification for a breach of privacy may be made on the grounds of benefits to the son.
At the same time, the son has a right to know medical information that may impact his health in order to exercise his autonomy by planning for the future. Alternatively, he also has the right not to know about his genetic risk. Although not equivalent to having no knowledge of his genetic risk, after disclosure of the family history with the C9ORF72 gene mutation he may choose to forego molecular testing.
Disclosure of the C9ORF72 gene mutation may have psychological implications such as stress, anxiety, and depression. Knowledge of the gene variant may lead to stigma, and may strain family and romantic relationships. There may also be work and insurance discrimination, although many developed countries have genetic non-discrimination legislation in place. Importantly the mechanism of disclosure itself (for example, supportive disclosure via a genetic counselor) may mitigate potential harms and facilitate informed decision-making.
Planning for the future may be a benefit of disclosure. Such planning may include acquiring life insurance and extended health coverage, securing social and practical supports to manage potential future symptoms and abilities, prioritizing valued activities, and preparing for a potentially shortened lifespan. Family planning may afford an opportunity for procreative beneficence. Knowledge of the C9ORF72 gene expansion may also provide opportunities to seek clinical trial participation as well as an opportunity to utilize novel therapies as they become clinically available. It is also possible that knowledge of his mother's condition may offer the son insights into her behaviors prior to estrangement. Finally, a negative test result may relieve him from unnecessary worry and fear.
As is often the case in neurology practice, technological advances outpace the law and professional guidance. In this case, legal precedents and ASHG guidelines currently do not establish a clear answer about the neurologist's duty to disclose the genetic risk. The neurologist may consider informing the patient's son of his genetic risk. Disclosure would maximize his autonomy by giving him an opportunity for life and family planning and possibilities for minimizing risks exist by way of supportive disclosure.
Benjaminy is a clinical ethics fellow at Providence Health Care and Provincial Health Services Authority, and a PhD student at the University of British Columbia (UBC). Young is a clinical ethicist at Providence Health Care, Vancouver, and adjunct professor in the department of occupational science and occupational therapy, Faculty of Medicine, at UBC. Dr. Tham is a neuropsychiatrist with the British Columbia neuropsychiatry program and clinical associate professor at the UBC. Dr. Unger is the director of ethics services at Providence Health Care, Vancouver, and clinical assistant professor at the School of Population and Public Health, UBC. Dr. Virani is the director of ethics services at Provincial Health Services Authority, Vancouver, and clinical assistant professor at the department of medical genetics, UBC.
Acknowledgements: The authors thank the Providence Health Care-Vancouver Coastal Health Elder Care Ethics Committee and Prof. Judy Illes for their insights on this case.
LINK UP FOR MORE INFORMATION:
•. American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure. Professional disclosure of familial genetic information http://http://www.cell.com
/ajhg/fulltext/S0002-9297(07)63510-1. Am J Hum Genet
•. Benussi L, Rossi G, Glionna M, et al C9ORF72 hexanucleotide repeat number in frontotemporal lobar degeneration: A genotype-phenotype correlation study https://content.iospress.com/articles/journal-of-alzheimers-disease/jad131028. J Alzheimer Dis
•. Hakimian R. Disclosure of Huntington's disease to family members: The dilemma of known but unknowing parties http://online.liebertpub.com/doi/abs/10.1089/109065700750065090. Genet Test
•. Heaton TJ, Chico V. Attitudes towards the sharing of genetic information with at-risk relatives: Results of a quantitative survey https://link.springer.com/article/10.1007%2Fs00439-015-1612-z. Hum Genet
•. Suthers GK, Armstrong J, McCormack J, Trott D. Letting the family know: Balancing ethics and effectiveness when notifying relatives about genetic testing for a familial disorder http://jmg.bmj.com/content/43/8/665. J Med Genet
© 2017 American Academy of Neurology
•. Tassicker RJ, Marshall PK, Liebeck TA, et al Predictive and prenatal testing for Huntington disease in Australia: Results and challenges encountered during a 10 year period (1994-2003) http://onlinelibrary.wiley.com/doi/10.1111/j.1399-0004.2006.00701.x/abstract. Clin Genet
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