Predictive, pre‐natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000

Abstract

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

SCA2 predictive testing in Cuba: challenging concepts and protocol evolution

“…Despite the fact that a similar situation has occurred in PND programs for HD in other countries (Simpson et al 2001;Simpson et al 2002;Creighton et al 2003), it has been a motive of great concern for us.…”

“…Since we are aware of the ethical, legal, and psychosocial implications of the predictive testing in unborn children which resulted from the nontermination of an affected pregnancy (Simpson et al 2002;Creighton et al 2003), we have offered to these families an interdisciplinary follow-up, but except for one of them, the rest have declined this service until now. This is another example of the decision-making process complexity when dealing with predictive studies for late-onset diseases.…”

When access is an issue: exploring barriers to predictive testing for Huntington disease in British Columbia, Canada

“…6 PT to determine risk status enables people to access benefits including: relieving uncertainty, reproductive planning, improved ability to plan for the future, access to support and research opportunities. [7][8][9] In keeping with the HD PT guidelines, 10 the PT process in British Columbia (BC), Canada usually involves three to four in-person appointments at the Center for HD in Vancouver to undergo physical exam, genetic counseling and education, psychosocial evaluation, results and follow-up 10,11 (Table 1). This process usually takes 4 weeks from initial appointment to the results session, and individuals are encouraged to bring a support person (eg, spouse), particularly to the results session (though this is not required).…”

“…9,12,14,15 Although PT for HD should be a carefully considered individual choice, there may be barriers to testing so that at risk individuals who would like to pursue testing cannot realize the potential benefits of PT. 16,17 Although the cost of PT is likely to be a significant barrier to testing in countries where PT is not covered by the healthcare system (PT is covered in Canada), other barriers to PT are likely to exist.…”

Developing a comprehensive, effective patient-friendly website to enhance decision making in predictive testing for Huntington disease

“…3,4 Testing uptake rates among those at 50% risk of developing the disorder vary widely, with estimates ranging from 5% to 25%, depending on the calculation methods used. 5,6 PT for the disorder is recognized as being an irreversible decision of great consequence, with psychological and emotional implications such as guilt (including "survivor guilt"), shame, fear, and other effects such as unintentional risk alteration for biological relatives. [7][8][9] As such, the international guidelines for HD PT recommend that individuals considering testing undergo in-depth genetic counseling, psychosocial evaluation, and assessment to ensure they have adequate support and are prepared for receiving this news.…”