By Martha Nance
Clinical teams and patients navigate genetic testing.
The decisions we make as we move into adulthood are unavoidably impacted by our childhood experiences. For children living in families affected by Huntington’s disease (HD), it is not surprising that experiences with HD color the transition from adolescence to adulthood.
- Should I stay close to home so I can help with an ailing parent (or a struggling partner)?
- Maybe if I move far away, I can just be me and nobody has to know about this family secret.
- At what point should I tell a girlfriend/ boyfriend about my family history?
- Why should I be serious about anything — for me there is no tomorrow, so I have to just try to enjoy today!
- Now that I am married, what about children?
One of those unique HD decisions is whether or not to have predictive genetic testing. Predictive (or pre-symptomatic) testing for HD has been widely available since the HD gene was identified in 1993, and should be performed in a clinical environment with the support of expert counseling. These may include geneticists or genetic counselors, as well as neurologists, psychologists and social workers wellversed in the family challenges common to HD.
Guidelines for health professionals performing HD predictive testing were originally published in 1994, with subsequent revisions made by the European HD Network, and the Huntington’s Disease Society of America.
Genetic testing for HD is an irreversible step; one cannot unlearn gene status. In that way, it is more akin to a surgical biopsy. For this reason, health professionals must help people who think they want to be tested to carefully consider the potential consequences of testing, and not just its benefits. Here are my top 10 recommendations for a predictive testing protocol.
Initially, our clinic works with the patient to review the testing process, including how many visits they can expect to make, who they will see, what the cost will be, and insurance coverage or self-pay requirements. We suggest to patients that it is advisable to get life, disability, long-term care insurance in place before undergoing testing.
While the constraints and allowable practices vary from institution to institution, we discuss our own center’s privacy, records retention and communications policies. We discuss “pseudonymous testing,” and explain that health professionals are legally required to document our work in the chart and that “shadow files” are no longer a viable option because the laboratory requires retention of results for its own auditing purposes.
Often family members want to test together, and while we accommodate these requests, we discourage siblings from testing together. In our experience, the impact of any one test result is so profound for a family to absorb that they should space these out over many months. Finally, we encourage, but don’t require, patients to have a partner or companion as they go through testing.
Spend Time with Family
A second stage of discussion before testing involves looking at factors that may impact the person’s risk. We ask if the family disease is genetically confirmed to be HD. If we have sufficient information, we calculate the patient’s a priori risk (50% with an affected parent, 25% with an affected grandparent if parents’ status is unknown, and much lower in the case where there is an affected sibling but no prior affected family members.)
If nobody in the family has ever had a gene test, the implications of a normal test result in an asymptomatic person are uncertain. Our group has tested patients who do not know their parent’s gene status. In these situations, a positive test result means that the patient’s parent will have an expanded CAG repeat. Some clinicians might decline to perform such a test, so much thought goes into this decision.
Become a Genetic Educator
An important part of our pre-testing counseling is educating the patient, at a level appropriate to their education and comprehension, about the biology of HD. We talk about chromosomes and genes, and autosomal dominant inheritance (50% risk to children of affected person). We need to introduce the CAG repeat expansion as the sole cause of HD. We discuss normal and abnormal CAG repeat ranges and the shades of gray — the high normal (mutable) range and the low abnormal (incomplete penetrance) range.
After setting the stage for a genetic understanding, we discuss meiotic instability of CAG repeats, particularly in male meiosis, and the relationship between CAG repeat length and onset age.
We make sure patients know, in advance of the moment that they receive results, that they should expect a result in the form of “two numbers” which correspond to two alleles (one from your mom, and one from your dad). In families with an older onset age, sometime the genetic testing result may not be conclusive, but in one of the “intermediate” ranges. Outlying issues like the possibility of two expanded repeats and nonpaternity (not readily proven with direct gene testing) may be explored if appropriate.
Review the Limitations of a Genetic Result
Genetic results cannot predict the age of onset, the disease course, and there are currently no disease-modifying treatments. One potential benefit of testing is the surveillance of clinical symptoms (neurological or neuropsychological monitoring), but the primary benefit of predictive testing is patient-specific.
Explore Reasons for Predictive Testing
We spend time discussing why the patient wants to undergo predictive testing — Why now? Why not last year? Why not next year? We find that most patients have thought a lot about why they want gene testing, but not as much about why they may not want testing. We discuss the potential negative impact of test results on self-perception, status of relationships within the family and community, employability, and insurability. We remind the patient that they still have the option to postpone testing, or not have testing at all. Some patients come for testing at a time when they are overtly symptomatic. Symptomatic and asymptomatic patients may return to talk about testing several times before getting gene tested.
Assess Psychosocial Status
A critical aspect of our pre-testing process is determining, as best we can, how the patient is likely to manage new knowledge that will come with the test results. It can be useful to have a trained psychologist address these issues. They will look at demographic information (marital status, employment status, age, general health, alcohol and drug use), the support system, their life history with HD, psychiatric history, and personal and family history of suicidal thinking or suicide attempts. As the major potential adverse effects of genetic testing are psychosocial, understanding the patient’s current psychological status and support system are important, and knowing whether he or she is among the approximately 20 percent of at-risk patients who have had suicidal ideation, helps the medical team to plan a support system appropriate to that patient. We encourage the patient to establish a relationship with a local counselor, if needed, before results are given.
Allow Time for Reflection
If the patient wants to proceed, the genetic counselor and psychologist usually meet with the patient first, and the neurologist a week later. This provides time to consider the preceding discussions, and opt out of testing, if desired.
We appreciate pre-test meetings to ensure that the patient fully understands what they are asking for, and the potential implications of the results. They may change their perspective; sometimes there are more questions, or they may need a local counselor. The patient should have time to reconsider the decision to be tested.
Ensure a Clear Timeline for Results
With a go-ahead decision, we document consent and promise to communicate that results can be given to the patient in two weeks. When the patient comes in to learn the results, they meet with the genetic counselor and/or the neurologist, who assure ample time for discussion. Follow-up may incorporate neurologic examination, neuropsychological testing, and/or support and counseling, as well as scheduling of a follow-up phone call.
Even gene-positive results can be surrounded with a backdrop of hope and an action plan for the future. Genenegative results sometimes come as a surprise or shock, and need to be worked through. We encourage patients, whatever their outcomes, to participate in research, advocacy, HD community educational support and fundraising activities.
Stick to a Protocol
We have found that this framework provides patients with the understanding and support that they need to optimize the benefits of testing, or to support them in the decision not to be tested. Our predictive testing team of genetic counselors, psychologists, and neurologists, utilize the skills and perspectives each has to educate, evaluate, and guide the patient to the testing decision that is best for them.