Predictive testing for Huntington's disease (HD) isn't just hard, but likely comes closer to the description given by Charles Sabine, a former NBC war correspondent. He said it was more terrifying than having a rebel hold a gun to his head. No wonder the HD "at risk" community and their families and friends struggle with testing decisions.
What to consider while making this decision for predictive testing? And if the decision is to test, what is the recommended procedure?
How many test? Before the gene was found, the Huntington's community had indicated they would want to have predictive testing. However when gene testing became reality a decade ago, many fewer -- in the range of 15% have chosen to test. When considering predictive testing, educate yourself about potential benefits and risks, how to interpret results that aren't clearly positive or negative, then proceed with thoughtfulness and caution.
What is known about the consequences of testing? Some answers can be found in the RESPOND-HD, a study conducted during 2006-2007. Investigators surveyed a total of 433 PREDICT and PHAROS participants about their experience with discrimination/stigma. The majority participants had tested positive for the mutant gene, others had tested negative. Discrimination events were broken down into separate categories:
|Personal (social relationship stigma from within or outside of family)||32.9%
|Insurance (medical, life, long-term care, disability, auto)||25.9%|
|Employment (denied jobs, fired from job, denied promotion, etc)||6.9%
|Transactional (health care providers, legal issues, housing issues, etc.)||4.6%
|Cumulative burden (any of the above reported)||46.2%|
They authors did not include another important category that has never been studied -- that of self stigma, and lowering of self esteem -- which can impair quality of life.
There have been several articles describing different aspects of RESPOND-HD results [Bombard Y 2009], [Erwin C 2010], [Williams JK 2010], [Williams JK 2010], [Bombard Y 2011] each with a different focus, but the bottom line:
- There is a lot of discrimination/stigma associated with being in an HD family whether tested or not
- More discrimination events are reported for those who test positive than negative
- More discrimination events are reported in those who knew their at-risk status from an earlier age
- More discrimination events are reported in those with higher education
One of these articles [Williams JK 2010] focuses on the the positive results of predictive testing including life planning and social support. However the perceived benefit most often occurred years after testing.
The Decision For those who do test, the more common reasons are to help with major life decisions: marriage, reproductive choices, career planning, etc., or simply the need to relieve the anguish of uncertainty. If choosing to test, approach with thoughtfulness and caution:
- Choose a time of lower stress -- not shortly after a parent's death, or just after learning of HD risk, etc. If depressed, anxious, or experiencing other mood or psychiatric problems, this should be treated before testing.
- Do not be coerced by family, friends, doctors or employers.
- Do not do it alone: Engage a trusted companion, family member, or friend for support.
- Identify a counseling person that you can contact if needed after testing.
- As much as possible have medical insurance, long-term care, and life insurance in place before testing.
- Ahead of time, try to visualize your response to a positive or negative test, or for one in the intermediate range.
It is important that you know, or that the counselor talk with you about the significance of CAG count number. One of 40 or more is usually necessary to develop the disease prior to old age, and 26 or below represents a negative test. Those with CAG counts between 36 and 39 may or may not develop HD symptoms -- depending on how long a person lives, or other epigenetic factors (environment or other genes that influence). In the case of a count between 27 and 35, the individual will not develop HD, but (mostly in male parents) may pass a longer CAG repeat to a child. This risk is greater in those with a higher range repeat (35) than those with a lower range repeat (27). The magnitude of risk for expansion is still under study.
The Process All of the following steps are recommended, but not required. If formal genetic counseling is done prior to predictive testing it follows a format that is similar among centers. It includes: an initial phone call to discuss family history and the testing protocol which is then followed by at least 3 visits. In sites that require a psychologist evaluation it may take another visit if this cannot be arranged on the same day. Though it may vary among centers, it can include:
- Genetics consultation where medical and family history are obtained, records reviewed, genetic counseling and education given, informed consent documents signed
- Psychological consultation/evaluation (not at all centers)
- Neurologic evaluation
- Blood collection obtained subsequent to these visits
- Discussion of results
- Followup counseling (not at all centers)
The genetic counseling process as recommended costs in the range of $1,500-$2,000. The gene test costs about $200-$300. Due to its cost (not all U.S. insurance carriers will pay for this) and difficulty traveling to centers for several visits, testing can be done through a local physician. There are no studies that have looked at how many tests are performed outside of centers. Though it is assumed that the center-based genetic counseling process is preferred, there are no studies that compare outcomes of those who test with or without the formal genetic counseling process.
An innovative study from British Columbia [Hawkins AK 2013] (where cost is not an issue) found that barriers to testing included:
- Distance traveled
- Inflexibility of testing process
- Length of testing process
- Paternalistic character
- Counseling requirements
They further showed that a program that allowed genetic counseling by telemedicine to local physician offices was often preferred, even when distance to the center was not large.
Predictive testing for children Predictive testing is not performed before age 18. The only genetic testing is when the doctor has high suspicion of Juvenile HD
Bombard Y, Veenstra G, Friedman JM, Creighton S, Currie L, Paulsen JS, Bottorff JL, Hayden MR; Canadian Respond-HD Collaborative Research Group. Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey. BMJ. 2009 Jun 9;338:b2175. doi: 10.1136/bmj.b2175. PubMed abstract
Erwin C, Williams JK, Juhl AR, Mengeling M, Mills JA, Bombard Y, Hayden MR, Quaid K, Shoulson I, Taylor S, Paulsen JS; I-RESPOND-HD Investigators of the Huntington Study Group. Perception, experience, and response to genetic discrimination in Huntington disease: the international RESPOND-HD study. Am J Med Genet B Neuropsychiatr Genet. 2010 Jul;153B(5):1081-93. doi: 10.1002/ajmg.b.31079. PubMed abstract
Williams JK, Erwin C, Juhl AR, Mengeling M, Bombard Y, Hayden MR, Quaid K, Shoulson I, Taylor S, Paulsen JS; I-RESPOND-HD Investigators of the Huntington Study Group. In their own words: reports of stigma and genetic discrimination by people at risk for Huntington disease in the International RESPOND-HD study. Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1150-9. doi: 10.1002/ajmg.b.31080. PubMed abstract
Williams JK, Erwin C, Juhl A, Mills J, Brossman B, Paulsen JS; I-RESPOND-HD Investigators of the Huntington Study Group. Personal factors associated with reported benefits of Huntington disease family history or genetic testing. Genet Test Mol Biomarkers. 2010 Oct;14(5):629-36. doi: 10.1089/gtmb.2010.0065. Epub 2010 Aug 19. PubMed abstract
Bombard Y, Palin J, Friedman JM, Veenstra G, Creighton S, Paulsen JS, Bottorff JL, Hayden MR; Canadian Respond-HD Collaborative Research Group. Factors associated with experiences of genetic discrimination among individuals at risk for Huntington disease. Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):19-27. doi: 10.1002/ajmg.b.31130. Epub 2010 Nov 10. PubMed abstract
Hawkins AK, Creighton S, Hayden MR. When access is an issue: exploring barriers to predictive testing for Huntington disease in British Columbia, Canada. Eur J Hum Genet. 2013 Feb;21(2):148-53. doi: 10.1038/ejhg.2012.147. Epub 2012 Jul 11. PubMed abstract