Case study

Our clinical genetics team was approached by a young man requesting predictive testing for an adult-onset neurodegenerative condition which had affected his grandparent and several of his grandparent's siblings. He had recently been informed of the risk and of the availability of predictive testing by his cousin. He was planning on having children within the next year, and if he was found to have inherited the condition, he and his partner were adamant that they would wish to pursue in vitro fertilisation (IVF) and PGD to avoid passing the condition onto their children. The man's at-risk parent was alive, and said not to be showing any signs of the condition. The man reported that he and his at-risk parent have a difficult relationship, and only see each other occasionally. When our client confronted his at-risk parent about the condition, the parent responded that they knew of the diagnosis and the availability of testing, but that they would commit suicide if they knew they were affected.

Possible solutions

This complex family situation presented an ethical dilemma to the treating team, challenging the principles of autonomy, beneficence and privacy and how to balance and prioritise these as they applied to different family members. A number of possible courses of action were considered. The following is a list of the possible solutions with a discussion of the ethical and practical considerations for each.

1. Deny the request for testing. This would protect the at-risk parent from harm; however, it would violate the young man's occurrent autonomy by precluding him from carrying out an informed decision that he has made about his own life and healthcare. It would also violate his long-term (dispositional) autonomy by denying him the option to plan and make decisions in relation to having children, and if he tests positive, to pursue options to avoid the birth of a child at risk of developing the condition.

2. Accede to the request for testing. This would provide the young man and his wife knowledge of his genetic status and if gene positive, reproductive options for preventing their children having the mutation. However, if the test is positive, this will reveal the parent's status as being affected. If the parent were to find out about their status, this would breach their express wish to not know if they will develop the disease. The parent's autonomy would be undermined by being exposed to personally significant information that they had deliberately decided not to seek for themselves. Furthermore, it may result in harm, as the parent is not psychologically or emotionally ready to receive the result, and is likely to receive it outside the context of a predictive testing programme which provides psychosocial supports. If the threat of suicide is a genuine one, there is the potential of causing substantial harm as a result of testing to the parent and to the extended family members and in particular the young couple who may feel guilty and responsible for the parent's death.

3. Direct testing of a pregnancy without first performing predictive testing on the son. By directly testing a pregnancy without first performing predictive testing, the chance of revealing the gene positive status of the son and affected parent is reduced from 25% to 12.5%, and thus the risk of harm to the at-risk parent is halved. This option requires the woman to terminate an affected pregnancy if the couple wish to prevent future generations being affected by the familial condition. This is ethically unacceptable to many people and is more likely to be unacceptable for adult-onset conditions than for conditions where the affected individual has morbidity from the condition from birth.

4. Use of ‘exclusion testing’ PGD. Exclusion testing can be used by couples where one partner is at risk of a genetic condition and does not wish to find out their own status, but the couple still wish to avoid passing the condition onto their children. Instead of directly testing for the gene mutation known to cause disease in the family, an indirect test is developed which tracks the gene copy inherited from the affected grandparent. For example, if a woman is at 50% risk of having inherited HD from her affected mother, to use conventional PGD, she would undergo predictive testing. In the event that she tests positive, the embryos will be tested for the gene mutation. The embryos found to have the mutation will be discarded. On the other hand, if she did not want to find out her own status, she could use exclusion testing prenatal diagnosis or PGD. She will not be tested for HD, and will not know her status. For exclusion testing PGD, all her embryos will be tested to determine the origin of the relevant gene. The embryos found to have inherited a gene copy from her mother (50% on average) will be discarded, without knowledge of whether they have the HD mutation or not. However, this has ethical costs. There is a 50% chance that the woman has undergone IVF and PGD treatment, with its associated risks and burdens to her, when there was no need to, as she has inherited the unaffected gene copy from her mother. In addition, a substantial proportion of embryos will have been discarded when there was no risk of the embryos being affected. It is reasonable to have ethical concerns about unnecessarily discarding healthy embryos, without regarding human embryos as having a right to life. It has been suggested that exclusion testing has an ethical advantage over direct testing in situations such as ours, where the adult son who is at 25% risk requests testing for reproductive reasons, against the testing wishes of their parent who is 50% risk. Exclusion testing would enable professionals to respect the wishes of the parent who does not want to know their status, and at the same time provide for the reproductive autonomy of the adult son and his partner, without causing distress to any party. This fulfils the ethical principles of autonomy and beneficence as they apply to all parties.8 ,9

However, the ethical costs of exclusion testing in this case are high. The young man is only at 25% risk of being affected and any potential embryos are at 12.5% risk of being affected. Therefore, if this option is pursued, his partner would be undergoing the risks and burdens of IVF treatment when there is a 75% chance that this is unnecessary. The couple would be discarding on average 50% of their embryos when there is only a 12.5% chance that any embryo is affected. In addition, the financial cost of performing IVF and PGD is largely borne by the couple in Australia, and is substantial.

The next steps

The various options were discussed with the couple. They were clear that any option that involved termination of a pregnancy affected by the familial condition was unacceptable to them. They were also clear that exclusion testing PGD was not an acceptable option for them, considering the financial burden and the 75% chance it would not be necessary. Therefore, the team needed to decide between offering and not offering a predictive test to the son.

In light of this, a separate genetic counselling appointment was arranged with the young man's parents to explore their wishes and family communication. The at-risk parent had a very close relationship with their own affected parent, and was deeply affected by that parent's cognitive decline and death from the condition. The young man's parent restated that they would commit suicide if they either developed symptoms or otherwise found out that they had the genetic mutation for the familial condition. This was a long-held conviction. The parent appeared cognitively intact and not depressed and did not have evidence of the familial condition. The parent described their son as ‘trustworthy’, and was prepared to provide a blood sample and consent for its use in PGD development ahead of their son making a decision about undergoing predictive testing.

The decision made

This dilemma has previously been discussed in the medical literature.8 ,9 The preferred resolution of cases such as these is to encourage the family to discuss their different perspectives and reach mutual consent on whether to proceed with predictive testing. The cases previously discussed in the literature have been resolved by parents acceding to testing, or accepting the result of testing without any apparent adverse outcomes.8 ,9 Although it may be possible to negotiate a ‘non-disclosure’ agreement within the family, where the young man is tested but the parent remains unaware of the result, this is complicated in the case presented here by the young couple's plan to pursue IVF and PGD as this would generally require blood samples from the young man's parents for test development. A request for blood samples for the purpose of PGD test development is likely to be interpreted as meaning the young man has tested positive for the condition.

It was clear that opposite testing preferences were strongly held by both parties, and that a compromise that completely avoided the possibility of distress to one or other party was not possible. The treating team had to make an ethical choice, and therefore undertook an analysis of the likelihood as well as the severity of harm to each party. A decision to deny or further postpone predictive testing in the young man would be harmful to him and his partner and his relationship with his parents, as well as impinge on his right to autonomy, and on his and his partner's right to reproductive autonomy. On the other hand, a decision to offer predictive testing only had a chance of resulting in an adverse outcome. The clinical team considered this chance to be quite low since for an adverse outcome to occur, the young man who had testing would need to test positive for the genetic mutation (25% chance) and this information would need to become known by the at-risk parent, and then the at-risk parent would need to actually suffer harm, either by carrying through with their stated intention to suicide or by experiencing significant irresolvable psychological distress. This is a long string of events of low probability. Even in the event that the test returned a positive result, given the commitment from both parties to non-disclosure within the family, the chance that the result would be disclosed to the at-risk parent, and that they would indeed suicide would be substantially lower (estimated by the team to be a few per cent overall risk). On balance, testing of the young man was judged to have a high chance of producing an outcome that respected the wishes and protected the rights of all involved. Had the son stated that he would reveal his result to his at-risk parent, we would not have offered testing as the risk of harm to the parent would have approached 25% and this would be too high a risk in our view.

In addition, the treating team came to the view that they had primary responsibility in this situation to the person presenting for testing, rather than an equal responsibility to him and his parent. This may also be seen as a tough decision. Genetic health professionals take a family-centred approach, which is ethically appropriate in general and in particular in genetics, where the information at stake is arguably family information. However, the interests and wishes of all family members do not always coincide, as was very apparent in this case. In these cases, the primary therapeutic and fiduciary relationship is with the person who has sought out help from the genetic health professional. If there is a clash of equal risk of harm to the client or client's family members, in principle the treating team is ethically required to prioritise the client's interests. While it is common to explore with the client the perspective of other family members, it is not ethically appropriate for the treating team to tell the client, here the son, that he should put his parent's interests before his own.

The treating team also did what it could to minimise the chance of any adverse outcome for the parent. First, blood samples were requested from the parents prior to the at-risk son having predictive testing for use in PGD should the test be positive. Second, a statement was developed in conjunction with the young man, declaring that as a prerequisite to proceeding with predictive testing, he undertook not to disclose the result of his test or any other information that may imply the result (such as undergoing IVF and PGD) to anyone other than his partner, to minimise the chance of his parent learning the result.

This complex case presents an approach to balancing competing rights within families at risk of late-onset genetic conditions, where family members have irreconcilable differences with respect to predictive testing. While it may not be possible to completely avoid harm in these situations, it is important to consider the actual magnitude of risks, and make every effort to limit the potential for adverse outcomes.