Being informed about informed consent

Key components. There are many factors for patients to consider when deciding whether to undergo genetic testing for epilepsy. Perceptions regarding the benefits and drawbacks can vary from one patient to another, and only the patient can determine whether the benefits of testing outweigh the drawbacks in their specific situation. Testing that seems straightforward to a clinician may not be so for a patient. As such, the process of informed consent is crucial to avoid harm and disappointment.

Informed consent. Obtaining informed consent is a process that must be tailored to each patient and their circumstances. A signature on an informed consent document is not sufficient in and of itself. Instead, it represents the final step of documenting the autonomous and voluntary decision made by a patient (or their proxy) after learning about and considering the potential positive and negative consequences. Situations that require particular sensitivity are those in which the patient is not an autonomous individual, such as a child or those who are cognitively impaired. In addition, the stakes are higher for those who are asymptomatic, but at risk to develop the condition or pass it on to their offspring.

Below are the six questions you should be able to answer during the process of informed consent for a patient undergoing epilepsy genetic testing:

1. What test are you recommending and who will perform it?
There are many genetic test options for epilepsy that vary by phenotype and test strategy such as single gene, multi-gene panels, or exome sequencing. It should be clear to the patient why this particular test and laboratory were chosen among the multiple options available.

2. Why are you recommending this testing?
The purpose of genetic testing must be clear. For those who are symptomatic, is the test to assist with a diagnosis, provide prognostic information, inform treatment decisions, provide risk information to relatives, or a combination? For those who are asymptomatic, the test may be to determine recurrent risks in a subsequent child, assess future risk to self, or both.

3. What results could your patient receive?
In general, genetic test results are either positive (pathogenic variant found), negative (no pathogenic variant found), or a variant of uncertain significance (variant found but uncertain whether it is pathogenic). A positive result in a symptomatic individual is the most desirable outcome of testing, but what does a negative result mean? It could mean that the condition does not have a genetic component or that the genetic component has not been identified yet. This can sometimes be a challenging concept to convey clearly. Testing may also identify a secondary finding, such as being a carrier for a disease they hadn’t realized – this is particularly relevant when ordering exome sequencing and important to discuss in advance. When variants of uncertain significance are received, additional testing for your patient and/or testing of other family members may be recommended to help interpret the clinical significance of the finding.  Families often benefit from understanding this possibility in advance of testing.

4. What are the potential benefits of this testing for your patient?
A test result that leads to better clinical outcomes for the patient and their family is the ultimate benefit, but is not a guarantee even when a pathogenic variant is found. Only certain genes and circumstances will alter care, such as a change of therapy or mitigating the need for surgery. For most people undergoing testing, the finding of a pathogenic variant confirms a diagnosis and provides prognostic and reproductive information. It may also help the individual and his/her family find closure and assimilate the diagnosis by having an answer to the question ‘why’. It also opens up the possibility of a more refined support network and access to research studies specific to that genetic cause.

5. What are the potential risks of this testing for your patient?
Genetic testing poses very little physical risk aside from those related to the sample collection, which are typically minor. Most potential drawbacks relate to financial, social, and psychological risks. Testing can be costly and may not be covered by insurance. Patients may need to weigh what they can afford in relation to what is available, and alternative testing strategies may need to be considered. The most common social risk is discrimination, for example by an employer, insurer, or the community. This is particularly relevant for those who are currently asymptomatic and/or those who face reproductive risks. Broaching these topics is an important part of the consent process so that patients can consider the possible ramifications of their choice to pursue a genetic diagnosis.

Psychological risks of testing arise from any type of test result. For those who receive a positive result, frustration may ensue by the lack of prognostic information available. Broad phenotypic ranges are not uncommon and patients may get stuck focusing on the worst case scenarios. Additionally, feelings of guilt or shame can surface, particularly in families that learn one or both parents passed genetic changes on to their child with epilepsy. Test results may also have unexpected consequences for relatives such as an unexpected risk to self or reproductive risk, and can occasionally reveal non-paternity. Importantly, in the setting of a negative result, the patient and/or relatives may be disappointed and this could be compounded if a significant out-of-pocket expense was incurred to complete testing. The patient may also wish to consider how such information might affect their identity and perception of self. Lastly, receiving a variant of unknown significance (VUS) result can be frustrating and can lead to a confusing situation in which the patient finds themselves in limbo until more information becomes available at some point down the road.

6. What are alternative options for your patient?
If the testing being recommended is prohibitively expensive, clinicians may need to identify other test options that may not be their first choice but which better accommodate the financial component of the decision. Also, patients may choose to wait to pursue testing for any number of reasons – lack of insurance coverage for the recommended testing, waiting for the insurance deductible to be met for the year, timing the sample collection with an upcoming procedure, or other reasons. In these situations, patients need to appreciate the risks associated with that choice, for example not identifying a condition that would alter treatment. Not pursuing a genetic diagnosis could also mean that a patient might need to undergo ongoing screening or imaging or other tests that could be avoided with a positive genetic test result.

Genetic testing is increasingly relevant to the care and management of patients with epilepsy, and has become commonplace in many epilepsy practices in the US. As the genomic revolution continues, clinicians can provide optimal care for their patients by being aware of the key components of informed consent for this type of testing, and facilitating discussions aimed at educating patients and assisting them in the most appropriate decision-making for themselves and their families.

Contributing authors:

Amanda Bergner is a certified genetic counselor and secretary of EpiGC. She has been involved in the clinical care of patients and families with epilepsy for many years at Johns Hopkins Hospital, and has conducted research about factors influencing the process of informed consent for genetic testing. Amanda currently works as the senior neurology product manager for Ambry Genetics where she focuses on developing innovative approaches to epilepsy genetic testing.

Susan Hahn is a licensed genetic counselor who is nationally recognized for initiating and leading research, outreach, education, and policy activities to facilitate and expand the responsible translation of genomic medicine in the clinical setting with a clinical focus in neurogenetics.  She has produced an abundance of educational resources,  including full semester courses addressing genome ethics, law and policy during her time at Duke and the University of Miami.  Susan currently works as a neurogenetic outreach specialist for Quest Diagnostics where she provides education regarding neurogenetic conditions and testing and utilizes feedback in the design of new and updated neurogenetic product offerings.

EpiGC is an informal collaboration among over 30 genetic counselors specializing in epilepsy genetics in clinical, research and laboratory settings. Our mission is to promote access to quality genetics services for patients and families affected by epilepsy through research, public policy/advocacy, education, and outreach activities. EpiGC’s goals are to 1) serve as a resource/provide education to the neurology community and advocacy groups; 2) promote the value of genetics and genetic counseling in the clinical evaluation of the patient with epilepsy; 3) promote the use of genetic testing laboratories that utilize the expertise of genetic counselors; 4) advocate for the improved reimbursement of genetic testing for epilepsy.

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