Confirming a diagnosis
The development of the DNA test has been very useful for confirming a diagnosis of Huntington’s Disease that a physician may make based on clinical signs. The DNA testing is especially helpful for those with earlier or later than average onset as well as when someone develops HD without a family history. A Canadian study reported that a quarter of those who tested positive were unaware of any family history of Huntington’s Disease. The reasons for this were misdiagnoses, family secrecy, and new mutations. About ten percent of patients with HD in a given generation are estimated to have experienced an increase in CAG counts from a parent who did not have HD but had a count in the unstable range (27-35).
There are other diseases with symptoms that overlap with Huntington’s Disease and the DNA test is a way to make sure that the diagnosis is correct. In the Canadian study cited above, 31.5 percent of those testing because of possible HD symptoms did not have the gene.
The test is also available for those who are not experiencing symptoms but want to find out whether they have the gene. Under these circumstances, the test is called ‘predictive.’
HD families are pioneers in this form of genetic testing and there were many concerns expressed from doctors, labs, psychologists, social workers, and advocates about how this could best be done. International guidelines were established for the predictive test. They can be found here along with the reasoning behind each component: http://www.hdfoundation.org/html/testwfn.php
These guidelines reflect concerns that people who take the test be well informed about the disease and genetic testing, be emotionally prepared for the results, and have the health, life, disability, and long term care insurance plans that they want in place before testing.
Other issues relate to being aware of how the results might impact other family members. A young adult might seek testing before getting married and having children, for example. However, a positive result would also communicate that an untested, at risk parent also had the gene, a result that the parent might be unprepared to hear.
Taking the test is always a personal decision. Friends who are unfamiliar with HD will often express surprise that the at-risk individual doesn’t immediately go and get a test. This is because they haven’t thought through the ramifications of learning that one will get a disease for which there is currently no treatment. Significant others may want someone to test because of joint decisions that will be made about marriage, having children, taking financial risks, etc. Ultimately however, it is the person at risk who must make the decision that is best for him or her.
Those who decide to have predictive testing are making a definitive decision. The testing process can be interrupted at any time, but you cannot “unring the bell” of a result once you have heard it. Deciding not to test is always provisional. It may help those at risk who decide not to test to realize that they are making a decision that can be revisited later. Their attitudes about predictive testing may change at a later time, they may become symptomatic and want to confirm the diagnosis, or a major treatment may become available which causes them to want to test.
A testing result of 40 or more CAG repeats means that the individual has tested positive for the Huntington's Disease gene. Below 27 repeats, the individual is negative for the Huntington's Disease gene and there is no need for concern for one's children.
|Unaffected||Normal||26 and below|
|Intermediate||27 – 35|
|Affected||Reduced Penetrance||36 – 39|
|Full Penetrance||40 and above|
However, sometimes a test result is not as informative as one would have liked. A result of 36-39 repeats is less predictive. In that range some will develop symptoms and some will not. Some researchers believe that this is the indeed the HD gene and that it would result in HD symptoms if the individual lived to an extreme old age.
A test result of 35 repeats and below means that the individual will not develop Huntington’s Disease. However, it is possible for those with 27 through 35 repeats to pass along an expanded number of CAG repeats which could result in an individual in a subsequent generation developing the disease.
For the most up to date information published about intermediate alleles, click here: HDLF: "CAG Counts: Intermediate Alleles"
As mentioned above, sometimes a clinical diagnosis of Huntington's Disease is not confirmed by a DNA test. To read about other possible diagnoses, go here: HDLF: "What if it's NOT Huntington's disease?"
The Consequences of Testing
Testing positive has obvious consequences. Anger, anxiety, depression are all normal emotions. There is likely to be a period of mourning for the more carefree future that the person hoped to have. People may try to put it out of their minds, change life plans, become involved in advocacy, do research to develop a proactive strategy of ‘best bets’ for healthy living, or develop some other coping strategy.
Less obvious are the consequences of testing negative. Certainly this is the preferred result, but many may feel ambivalent about ‘celebrating’ when other friends and family members have not been so fortunate. Sometimes survivor’s guilt will cause people to do too much in the way of advocacy, fundraising, and support for others rather than keeping volunteer work in a healthy balance. And life doesn’t change over night. It takes awhile to stop watching for symptoms and it is not uncommon for those who test negative to wonder if a mistake was made with the test.
Even deciding to test may bring about certain unanticipated consequences because another at risk family member or friend in the support group could feel uncomfortable about their own choice not to test and become distant.
The test has been available for over a decade and researchers have done a number of studies about how people and families react to it. We will be reviewing those studies and summarizing and commenting on them on the Lighthouse.
Here on the HD Lighthouse Family site, we are presenting stories submitted by our readers about their own experiences. Whatever your thoughts and emotions are, they are shared by others. Links to personal stories appear on the left side of the page.
For those of you at-risk, information on preparing for the future can be found in Phil Hardt’s section on navigating the sometimes turbulent waters of HD, HDLF:Navigating Life particularly the section Making Better Decisions Now.
D Falush et al, "Measurement of Mutational Flow Implies Both a High New-Mutation Rate for Huntington Disease and Substantial Underascertainment of Late-Onset Cases." American Journal of Human Genetics 2001 February; 68(2): 373–385.
S Creighton, et al, "Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000." Clinical Genetics 63 (2003), 462–475.