Initially, testing was done mainly by detecting the linkage. After the gene was discovered in 1993, testing could directly identify the gene itself.
The test can be done by sending blood samples to a laboratory, whether to detect the gene and confirm the diagnosis, for presymptomatic testing of carriers and high-risk candidates, or for prenatal testing. Over the years, the test has proved its effectivity and was incorporated as a National Health Service test in the UK 10 years after its establishment.2
The cost of the laboratory DNA test ranges from $200 to $300.2 In addition, there is the expense of “confirming the diagnosis,” which typically occurs in persons with a suspected diagnosis, in the absence of family history as in cases of adoption or a deceased parent, and in the event of a de novo mutation.
Candidates often choose to pay for the test out of pocket for fear of disclosure to third-party payers such as health insurance companies and for fear of exposure of their private information to their employers and potential discrimination.5 Sometimes they give false information about their identity or ask for the test anonymously.4
Consequences of the test results
The results of genetic testing for Huntington disease must be taken into consideration. The consequences of the test outcome should guide recommendations about who should be tested.
Researchers have assessed the risk of depression in patients found to have the HD gene. In 1986, when the test involved the genetic linkage, not the direct gene, Brandt and colleagues5 conducted a study of the genetic marker of Huntington disease. Reactions to the test ranged from relief to sadness, but there was no severe depression in the short term at least.
A study published in 1997, after determination of the direct gene, evaluated predictors of adjustment over a 1-year period among 52 candidates who tested positive for the HD gene and 108 candidates who tested negative. The study used the Beck Hopelessness Scale (BHS) and Beck Depression Inventory (BDI) to assess adjustment. Those who had a better adjustment were married; had no children, so there was no guilt about transmitting the disease to their offspring; or were close to the age of onset.6
A review showed that carriers and non-carriers differ in their short-term but not their long-term adjustment. It also demonstrated that adjustment status before the test is the main determinant of post-test adjustment: “Carriers show either no changes from psychological adjustment before testing or only short term increases in hopelessness.”7 The authors recommend that genetic testing be preceded by and be done in the context of psychological or psychiatric counseling.
Overall, predictive testing has not resulted in suicide attempts. Revised guidelines recommend at least two or three pre-test sessions that involve a genetic counseling session, a psychological assessment, and a neurological examination, although these recommendations should be considered on a case-by-case basis.8 In general, patients cope well with test results.
Effects on the family
Some studies have reported higher rates of divorce among carriers in the first 6 months after they received the test results, compared with non-carriers.8 Some candidates denied depressive symptoms in the Minnesota Multiphasic Personality Inventory (MMPI), yet their partners confirmed the symptoms; the lie score was higher among females. There were reports of guilt among carriers who have children. Some partners reported hopelessness and less sexual satisfaction.
Pre-test marital assessment is recommended, and the reversal of roles in marital relationships must be addressed. The extended family should also be involved. Maximizing connection and autonomy throughout the phases of the disease should be stressed.
Prenatal testing is less frequently requested, primarily because many high-risk candidates have undergone the test before pregnancy and decided not to become pregnant. Presymptomatic testing during pregnancy has a profound effect on the mother who finds out that she is a carrier. If prenatal testing reveals that the fetus carries the HD gene, the couple can undergo severe distress whether they decide to terminate the pregnancy or not.
Preimplantation genetic diagnosis (PGD) is available for couples who want to avoid termination of pregnancy: “Most often PGD tests are performed on single cells biopsied at the eight-cell embryo (day 3 of development). The genetic analysis for monogenic disorders such as HD takes advantage of PCR to amplify the DNA and for detection of the repeat sizes for each chromosome.”4 The drawbacks of PGD are “allele dropout,” the high cost of the procedure, and the low success rate, yet it can still be considered.
Dr Bishay reports no conflicts of interest concerning the subject matter of this article.
1. Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306:234-238.
2. Harper PS, Lim C, Craufurd D. Ten years of presymptomatic testing for Huntington’s disease: the experience of the UK Huntington’s Disease Prediction Consortium. J Med Genet. 2000;37:567-571.
3. The Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971-983.
4. Myers RH. Huntington’s disease genetics. NeuroRx J Am Soc Experimental NeuroTherapeutics. 2004;1:255-262.
5. Brandt J, Quaid KA, Folstein SE, et al. Presymptomatic diagnosis of delayed-onset disease with linked DNA markers. The experience in Huntington’s disease. JAMA. 1989;261:3108-3114.
6. Codori AM, Slavney PR, Young C, et al. Predictors of psychological adjustment to genetic testing for Huntington’s disease. Health Psychol. 1997;16:36-50.
7. Meiser B, Dunn S. Psychological impact of genetic testing for Huntington’s disease: an update of the literature. J Neurol Neurosurgery Psychiatry. 2000;69:574-578.
8. Tibben A. Predictive testing for Huntington’s disease. Brain Res Bull. 2007;72:165-171.