Guide To Genetic Testing
What is predictive genetic testing?
Genetic testing is used to look at your genes (the blueprint or DNA instructions you inherit from your parents) to detect mutations or gene changes that cause disease. Predictive testing (sometimes also referred to as pre-symptomatic testing) is testing of individuals prior to signs or symptoms of disease. Genetic testing can help confirm or rule out the presence of a mutation, and thus help determine whether a person will develop the genetic disorder previously experienced by a family member found to have a genetic mutation.
How do I know if I’m ready to undergo genetic testing?
This is a difficult, complex, and very personal decision. No one can make this decision for you and should not make this decision for you. Being influenced by others may result in having very negative psychological responses to test results. With that in mind, it is important to take the time to determine whether genetic testing is right for you.
In recent conversations with a genetic counselor and individuals who got genetic testing done, we tried to determine whether certain common characteristics exist between individuals who do well after testing and individuals do not do well after testing.
What genetic counselors and other at-risk individuals say:
Individuals who do well: From the counselor perspective, individuals who go on to pursue testing and do well are ones who have put a lot of work into really understanding and coming to terms with the decision they are about to make and the impact it will have on their life going forward. They have gone through the entire genetic testing protocol (see below for what this entails), discussing their concerns with their genetic counselor at length, sometimes over multiple sessions. These are individuals who have thought about their disease and genetic testing ahead of time and once they get their result, these are individuals who often re-evaluate and make changes in their life, such as quitting jobs that no longer bring them purpose or traveling around the world. In speaking with other at-risk individuals who pursued testing and responded well to a positive result (meaning that they carry a disease-causing mutation), many said that they wanted to plan ahead and needed this knowledge in order to make a more informed decision about their future (such as whether they should have a child, join a trial, save for retirement/care).
Individuals who don’t do well: From the counselor perspective, individuals who do not pursue testing or do not respond well to testing are those who have pre-existing psychological issues, such as depression and/or anxiety. These are individuals who do not make future plans and who do not have adequate support (including someone to talk to about their decision outside of the counselor or other medical professional). From other at-risk individuals’ perspectives, those who have felt or expressed the following views have usually not gone on to get tested: individuals who avoid thinking about the disease and those whose hope relies in not knowing about their future with the disease.
If you are on the fence and feel like you are constantly changing your mind, then it is probably best to wait and give yourself more time to become comfortable with a decision. For some, it took years to reach this point, for others it was immediate. It may also be helpful to know that you are not alone; less than 20% of individuals with a family history of dominantly inherited neurological diseases even contact a genetic counselor.
What research studies on genetic testing in DIAD say:
Studies have shown that some people who receive a positive genetic result (i.e. tested positive for carrying the mutation) experience increased depression and anxiety immediately to 3 months following testing. One year after testing, depression and anxiety levels seemed to return to baseline. For some people, results (even if confirming a mutation) can serve as a relief in eliminating uncertainty. The results help provide important information for making decisions on whether to join a clinical trial, make lifestyle changes, retire early, or have a baby. For others, finding out their results can be an enormous emotional burden to carry. They find it difficult to face a disease with no treatment or cure currently available (Paulsen et al., 2013). Although these results provide evidence that individuals can return to their “normal” depression/anxiety levels one year following testing, it should be noted that no studies exist following the long-term psychological impact of genetic testing. It should also be noted that these studies only include data on individuals who have gone through recommended genetic counseling protocols and who have given considerable thought to their testing.
Before going for testing, consider speaking with a psychologist who is specialized or has experience in treating people who have a dominantly inherited disease in their family. They may help determine whether you are emotionally ready for undertaking the testing process. If you are having trouble finding one, genetic counselors may be able to make some recommendations.
I’m ready to get tested – what now?
Many people worry about discrimination based on their genetic test results, and rightly so. With the advent of digital patient records, informed patients should make every effort to protect their and their families’ privacy. In 2008, the US Congress enacted the Genetic Information Nondiscrimination Act (GINA), to protect individuals against discrimination by their health insurance provider or employer. However, GINA does not apply to long-term care, disability, or life insurance providers. Thus, it is important to obtain these policies before undergoing genetic testing.
Consider obtaining life insurance
Consider obtaining long-term care insurance
If you can, obtain a copy of your parent’s or family member’s positive test result (i.e. the genetic testing report they received listing the nucleotide or amino acid change; it should also have their accession or testing ID number). If you do not have this information, see below.
Begin setting up a support system. Many sites require that you have a support person with you, so you should decide who this person will be. Counselors recommend it be someone who is not at-risk of inheriting a DIAD mutation. Getting tested can be an emotional rollercoaster and having 1-2 people (other than your partner or support person) to talk to about this process can be very helpful. It may also be helpful for the partner/spouse to set up a support system as well.
Find the right genetic counselor for you (important questions to ask or things to consider when looking for one):
They have previous experience working with dominantly inherited Alzheimer’s disease or Huntington’s disease.
They were recommended/found through the National Society of Genetic Counselors or your local Alzheimer’s Disease Research Center.
They follow the Huntington’s Disease genetic testing protocol.
They are aware of your privacy concerns and are willing to take steps to keep your genetic information outside of your medical records: i.e. they are willing to keep you off their electronic records and/or only keep you in their paper files. They possibility allow you to test under a pseudonym.
Thoughts on who to tell: Individuals who have undergone testing have recommended telling close friends that you were undergoing the process, but to do so without giving away specific dates of appointments. That way you don’t feel pressure to respond to calls or texts, and instead have an opportunity to process your results on your own before reaching out to others. It can often be hard to discuss these with family (as everyone’s perspective and way of dealing with the disease is different). In those cases, at-risk individuals also reached out to a fellow DIAD family member who served as a support person.
What should I expect when going through genetic testing?
No. of sessions: ~2-3 sessions
The sessions consist of one visit with a physician to order the test (not needed if the genetic counselor works with an MD who can order the test or if the counselor is able to order the test), one visit for a pre-testing genetic counselor session and one visit for a post-testing genetic counselor session. Please note that some genetic counseling sites will also require a psychological evaluation prior to testing.
Avg. length of a session: 30 min – 1.5 hr
Type of tissue collection: blood, saliva, cheek swab
Avg. wait time before receiving result: 1 – 3 months
What happens in the first (or pre-testing) session with a genetic counselor:
The pre-test genetic counseling session should review the patient’s personal and family history, and inform the patient of the benefits, risks, and limitations of undergoing genetic testing. In session 1, the genetic counselor will discuss the inheritance of the genetic mutation of interest. They should help answer any questions you may have regarding genetics, including: 1) what is an autosomal dominant disease, 2) how are genetic mutations passed on in the family, 3) what are the chances of getting the disease, 4) what are the chances of offspring or children getting the disease, etc. They will draw a family tree which includes who has been affected by the disease and whether or not these individuals have been tested. This is also when you will provide a report of any family member’s genetic testing results, if you have one.
During this session, genetic counselors will also help walk you through potential scenarios and your responses to a negative and positive test result. This is your chance to discuss and think about what it would be like to find out your were positive for the mutation or negative for the mutation, and how would it affect your mental state/feelings, life plans/goals, spouse, relationships with others, family relations, financial matters, reproductive options, etc.
In the last part of session 1, the genetic counselor will ask if you are ready to provide tissue for testing. If you agree to proceed, you’ll need to work out how the payments will be made. Make sure that if you are working under a pseudonym, you either bring cash or a cashier’s check to the appointment. After that, blood, saliva, or cheek swabs will be taken and then placed in an envelope to send to the test facility. This is a good time to work out any more logistics with your counselor (i.e. how long you’ll have to wait until your result is ready, how long they recommend you wait, whether you prefer them to wait to open your result/envelope until you are there, how you prefer to be contacted, etc.). This is your chance to let the genetic counselor know your preferences for receiving this important news.
For both sessions, you may be asked to bring in a support person. They often require or recommend that this person not also be at-risk for the same gene (i.e. a sibling). If you intend on bringing a spouse or partner, the counselor should help prepare them for the result as well. Some spouses have not had as much time to deal with the social and psychological consequences of hearing a loved ones’ result, so it may be helpful to speak with a loved one about this earlier.
What happens in the second (or post-testing) session with a genetic counselor:
In session 2, the genetic counselor will ask whether you are ready to hear your result. Other at-risk individuals recommend that you not try to “read” into your genetic counselor’s behavior, it will in no way reflect your genetic status. Once you are ready, the counselor will reveal your test results, in some cases this is opening an envelope. There have been many cases where individuals decide to wait to hear their results, so there is no pressure to do it any sooner than when you are ready. Either way, the individual should seek a mental health professional or psychologist to help digest the results on a more long-term timeline than the genetic counselor can provide.
What is the cost of genetic testing?
Cost: $200 - $2,000
These numbers are according to the NIH Genetics Home Reference. If you break down the costs, it is ~$250-$450 for the genetic test (usually with Invitae, Prevention Genetics, or Athena) and ~$250-$350 per genetic counselor session. If you are enrolled in the DIAN Observational study or the DIAN-TU clinical trial, these costs will be covered. Insurance may cover some/all of these costs; however if you wish to be tested under a pseudonym, you may be required to pay out of pocket for some of these services.
What are some consequences I can expect following genetic testing?
Transient increased anxiety and/or depression (extreme and catastrophic events have been reported,
but are rare)
Improved understanding and knowledge for assisting future decisions
Heightened awareness of genetic status, disease stigmatization, and possible discrimination
Socioeconomic issues related to the need for long-term follow up of individuals with positive result
What if I don’t have my parent’s/family member’s genetic information?
The genetic counselor or ordering MD should request panel genetic testing. This consists of testing all three genes’ (APP, PSEN1 and PSEN2) sequences entirely to determine if a DIAD-causing mutation is present. Panel testing can be 2-3 times more expensive than targeted testing of a specific gene and mutation. If possible, it is best to be tested at the same lab at which a relative with a positive result was tested, as the lab can compare your results with your relatives.
What are some caveats and other considerations of genetic testing I should be aware of?
The presence of a mutation does not always result in disease – the existence of escapees:
Most studies have shown that a person’s age of onset for developing disease is very close to the age in which their previous family members starting showing symptoms of the disease. For example, if the father developed Alzheimer’s at 45 years of age then the son who tested positive would likely develop the disease between 42-48 years of age. However, there have been instances where individuals test positive for a mutation but are 10-20 years past the age of onset of their parent and have still not developed the disease. Current studies are underway to determine how this occurs in these individuals. The existence of these individuals, however, means that if an individual tests positive for a disease-causing mutation, they do not have a 100% chance of developing disease, but rather a 99.5% chance.
Be careful of direct-to-consumer testing services.
Many genetic testing companies are offering consumer genetic testing (i.e. 23andme), and initially it can seem less costly and more hassle-free compared to the traditional genetic testing route. However, individuals who are at-risk of DIAD should be careful when considering these tests. A recent article in the NY Times revealed that a commercial genetic test misdiagnosed a man with a PSEN1 mutation with no family history of the disease. He found the results disturbing. He then tested with another company and no mutation was found. This story should serve as a lesson for consumer genetic testing, as these tests are not FDA approved for testing mutations that cause genetic neurological disorders and often (as illustrated in this story) have poor accuracy. To read the article: https://www.nytimes.com/2018/09/15/opinion/sunday/23andme-ancestry-alzheimers-genetic-testing.html
Paulsen JS, Nance M, Kim JI, Carlozzi NE, Panegyres PK, Erwin C, Goh A, McCusker E, Williams JK. (2013). A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases. Progress in neurobiology, 110, 2–28. doi:10.1016/j.pneurobio.2013.08.003.
Can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833259/