Psychosocial implications of uncertainty. As navigators of genetic testing, genetic counselors have seen it all – smooth seas, choppy waters and even the rare tsunami. Genetic testing sounds, well, so promising. Huge gene panels for epilepsy, whole exome sequencing – guaranteed to find an answer, right? Wrong. And let’s not even talk about secondary (incidental) findings, variants of uncertain significance and (gulp) non-paternity. While our technology has changed, navigating the choppy waters of psychosocial issues in genetic testing has not. Previous EpiGC posts to this blog have highlighted the challenges inherent to interpreting variants of uncertain significance. Now let’s talk about the psychosocial implications of dealing with uncertainty.
Finding the why. People often look to genetics to figure out the “why”. In his seminal book “Psychosocial Genetic Counseling”, Dr. Jon Weil talks about the individual’s fundamental search for meaning in the face of an unexpected event, such as epilepsy in a child. The search for a diagnosis may be one component of this larger search for meaning, in which this child and this condition finds its place in the family’s life. As scientists, we tend to focus on scientific explanations but don’t always recognize that these may not satisfy the fundamental search for meaning.
In the field of epilepsy genetics, genetic testing is the means to the “why” – let’s find that gene variant, and all is explained. However, introducing the possibility of a genetic epilepsy may also provoke feelings of iatrogenic guilt, or guilt incited by health care providers. Now we’re talking genetics – parents may think to themselves: did I do something to make this happen? Are my other children at risk?
In a recent study of multiplex families with epilepsy in Epilepsia, Sorge and colleagues reported that unaffected individuals with a higher perceived risk of an epilepsy-related genetic variant also had a higher prevalence of depression. Having discussions about genetic causes of epilepsy raises the likelihood of heading from the deep waters of guilt into the dangerous shallows of shame. Conversations about how we are all carriers of genetic disease and we can’t pick our genes doesn’t fix those feelings, but helping to recognize and acknowledge them is often an important first step in the process.
The principle of uncertainty. In general, we prefer certainty to uncertainty. Dr. Dennis Lindley, champion of Bayesian statistics, once said: “Uncertainty is a personal matter; it is not the uncertainty but your uncertainty”. Unfortunately, life is filled with uncertainty – and so is genetics. There are many ways which uncertainty can raise its fuzzy head in epilepsy genetics – uncertain diagnoses, variants of uncertain significance, unknown prognoses. With increased use of large gene panels and exome sequencing, there are more avenues to diagnosis very rare conditions. However, some of these diagnoses are so rare that, realistically, we can’t tell families any more than they already know from their child.
Dealing with uncertainty. It seems that the only thing that is certain is that there is always uncertainty. In the face of uncertainty, what can we, as clinicians, do? Here are some strategies that may help address the emotional impact of uncertainty during the genetic counseling session.
Focus on what is certain or known in the situation. One way to help cope with the unknown is to focus on the known. For example, while a negative result means we don’t have a diagnosis, it also means that we have ruled out a long list of conditions (within the limits of testing, of course). Even though we may not have an underlying genetic diagnosis, we can refer our families to available epilepsy advocacy groups, such as the Epilepsy Foundation or CURE. Lack of control is what makes uncertainty so hard – but focusing on the known helps us gain a bit of that control back.
Provide a range of outcomes: worst case to best case. Families and patients often say they’d like a diagnosis to help inform prognosis. It’s normal to want to know what to expect in the future or to want to feel confident that you are doing everything you can for your child. Unfortunately, information about prognosis or management may not be available for very rare conditions. And to make things more complicated, some conditions have reduced penetrance and variability, meaning that we can’t always predict what a result means for a family. Discussing the possible range of outcomes is one way to provide information in uncertain situations – we may not know exactly what types of seizures your child will have, but here is what has been reported and here is what we will do to monitor it. While this strategy doesn’t take away the anxiety, it may help mitigate it by talking through the possibilities and helping families prepare for different outcomes.
Discuss probabilities of occurrence to provide perspective. Besides discussing a range of outcomes, consider framing each outcome in terms of its probability. For example, approximately 40-60% of children with tuberous sclerosis have intellectual disability, but children who have not had infantile spasms tend to have better cognitive outcomes. While this doesn’t help us predict how a specific child may do, it does give the family some information to work with. Ask families how those numbers make them feel and if they are what they expected. A low probability event perceived as significant is not always reassuring, but probability numbers can help a family to focus their concerns on the most likely outcomes.
Explore and compare scenarios. When faced with an uncertain outcome, it may be helpful to explore the possible outcomes. One concern of families with children with presumed genetic epilepsy is recurrence risk – what is the chance this could happen again? While this may seem like a probability discussion, for many families this is actually a binary question – either a child is affected or they aren’t. Exploring possible scenarios may allow patients and families to realize that they have coping strategies, no matter what the situation may be. Alternatively, it may help them determine what scenarios are unacceptable and in turn help guide their decision-making processes.
Find the hope. In my journey as a genetic counselor I’ve been fortunate to work with many genetic counselors and medical providers who have helped me navigate the seas of uncertainty. As a student, one of my mentors would remind us to “find the hope”. In the face of uncertainty there are lots of opportunities for hope – it’s our job to help patients navigate the seas to find them.
Christine Spaeth is a member of EpiGC and a licensed, certified genetic counselor at Cincinnati Children’s Hospital Medical Center. Christine is the Clinical Manager for the 20+ genetic counselors in the Division of Human Genetics at CCHMC. Her areas of interest include neurology, particularly epilepsy. Christine earned her undergraduate degree from Johns Hopkins University and her Master’s degree in medical genetics from the Genetic Counseling Program at the University of Cincinnati.