Predictive Testing For Huntington's Disease Research Articles

Understanding the decision to take the predictive test for Huntington disease

The predictive test for Huntington disease (HD) has allowed those at risk to determine gene status prior to symptoms. The purpose of this research was to understand the motivation and the anticipated reactions of those requesting the test. Forty persons at 50% risk for HD and 31 companions participated in a structured personal interview as part of the predictive test protocol. Reasons for taking the test centered on the reduction of anxiety and uncertainty associated with being at risk and enhanced planning and decision making. Participants also believed that taking the test would produce more positive than negative outcomes. With a favorable result, most anticipated a reduction of anxiety, a more normal future, and relief knowing their children would be at a very low risk. Most also cited benefits as more likely than consequences with an unfavorable result. Making the most of life, easier planning, and reduced uncertainty were rated as more likely than any of the adverse impacts, including short-term depression and becoming frightened. Almost all participants (95%) said they would rather learn that they have the HD gene than remain at 50% risk. The uncertainty, anxiety, and chronic stress associated with being at risk appears to underlie the motivation of many seeking the predictive test for HD.

Predictive testing for Huntington disease: II. Demographic characteristics, life‐style patterns, attitudes, and psychosocial assessments of the first fifty‐one test candidates

Predictive testing was offered to individuals at-risk for Huntington disease living within a 100-mile radius of Vancouver, BC. Ninety-five at-risk individuals, representing approximately 12.6% of eligible candidates in this area, have enrolled in its first 16 months. This paper reports on the psychosocial characteristics of the first 51 at-risk individuals to complete the initial assessment. Two-thirds of the candidates are female with a mean age 39.3 years. They derive from higher socioeconomic backgrounds. Reasons for taking the test included planning for the future, concern for their children, and reducing uncertainty. Only 29.4% of candidates would both desire prenatal testing and terminate a high-risk pregnancy. Results on the SCL 90(R), General Well-Being, and other scales indicate that the candidates' mental health is representative of the population, but as a group, they are more resourceful. The tests identified individuals who needed further assessment on the basis of previous and current psychiatric functioning and social support. No candidate was a high immediate suicidal risk. The process of personal assessment has had beneficial effects on personal growth. The self-selection of a healthy group of candidates emphasizes the need for continued assessment and support as possibly less healthy candidates register for predictive testing programs in the future.

Predictive testing for Huntington disease: I. Description of a pilot project in British Columbia

The discovery of DNA markers linked to the gene causing Huntington disease (HD) has allowed the development of predictive testing programs for persons at-risk. A pilot program was established in British Columbia in November 1986. Ninety-five persons are currently enrolled. The major objective of this project is to introduce and evaluate a protocol for the delivery of test results to persons at-risk for HD. The criteria for entry and details of the psychosocial assessment before and after receiving a modified risk are presented. The guidelines that are developed from this project will have major applications for predictive testing programs for other late onset autosomal dominant disorders.

Prenatal exclusion testing for Huntington's disease: a problem of too much information.

At eight weeks of pregnancy a couple were informed that the prospective father's mother had died of Huntington's disease (HD). There were no living affected members in the immediate family to confirm the diagnosis. By inspection of the local genetic register, it was established that it was indeed HD segregating in the extended family. Genotyping of the prospective mother and father, the father's unaffected father, and his unaffected maternal grandmother was carried out using a battery of polymorphic DNA markers, including a new probe which has a very low recombination rate with the HD locus. Analysis of DNA from a chorionic villus sample taken at 10 weeks of pregnancy showed that the fetus must have inherited a chromosome from its father's affected mother. Its risk of developing HD was 47%. If the genotype of the unaffected maternal grandmother was taken into account, the risk was reduced to 42%. Neither risk was considered acceptable by the prospective parents and the pregnancy was terminated at 12 weeks' gestation. Prospects for future pregnancies are good, with a 50% chance of having a child whose risk of inheriting the HD gene is less than 1.5%. In retrospect it was noted that although genotyping of the maternal grandmother had refined the fetal risk, it had also nearly contributed to an inadvertent and unwanted predictive test for HD on the father. This case makes the point that in prenatal exclusion testing, linkage information must be generated with considerable care.

Presymptomatic detection of Huntington's disease.

Because of the usually late onset of Huntington's disease (HD) most sufferers have reproduced and passed the HD gene to about one half of their offspring before they themselves develop symptoms of the disease. Genetic counseling of persons at risk of HD would be greatly facilitated if the gene could be detected presymptomatically. At present, there is no suitable predictive test for HD, but many approaches currently being investigated show some promise. These approaches are reviewed and critically evaluated.