Nance MA. Genetic counseling and testing for Huntington's disease: A historical review. Am J Med Genet B Neuropsychiatr Genet. 2016 May 13. doi:10.1002/ajmg.b.32453. [Epub ahead of print]
This manuscript describes the ways in which genetic counseling has evolved since John Pearson and Sheldon Reed first promoted "a genetic education" in the 1950s as a voluntary, non-directive clinical tool for permitting individual decision making. It reviews how the emergence of Huntington's disease (HD) registries and patient support organizations, genetic testing, and the discovery of a disease-causing CAG repeat expansion changed the contours of genetic counseling for families with HD. It also reviews the guidelines, outcomes, ethical and laboratory challenges, and uptake of predictive, prenatal, and preimplantation testing, and it casts a vision for how clinicians can better make use of genetic counseling to reach a broader pool of families that may be affected by HD and to ensure that genetic counseling is associated with the best levels of care.
From the article:
Despite the high levels of interest in genetic testing that CCHD survey respondents expressed in the 1970s, before the HD gene was discovered, clinical reports have shown that in most countries the uptake of tests has been relatively low, with a variable rate of predictive testing ranging from an estimated 10% in the United States to as high as 80% in the Netherlands. Even in the Netherlands and Australia, two countries with a relatively high uptake of predictive testing, prenatal, and/or preimplantation tests are uncommon. Tassicker et al.  report on 2,036 predictive tests and 63 prenatal tests over a 10-year period, and van Rij et al. [2014a,2014b] report on 262 prenatal and 54 preimplantation tests, also over a 10-year period. In the van Rij study, a number of pregnancies were continued to term after prenatal testing revealed a gene positive fetus. Moreover, Bernhardt et al.  document a declining rate of predictive test uptake at a single center in Germany over a 10-year study period…
Despite the complex psychosocial dynamics within HD families and the psychiatric symptoms of the disease itself, most of the many studies of the psychosocial outcomes of predictive testing have confirmed the early findings of Almqvist et al. , whose worldwide survey of centers performing predictive tests showed a very low risk of severe or catastrophic mental health outcomes (e.g., hospitalization, suicide attempt, or suicide; see Table I).
Unusual clinical HD predictive testing situations abound, creating fertile material for discussions of the ethical, legal, and social implications of these tests. For example, the literature has included discussions about the testing of at-risk children at parental request, prenatal or predictive testing of individuals when some family members do not want to know the results (e.g., prenatal testing at maternal request when the at-risk father does not want to know or predictive testing of an adult child with a 25% risk of HD when a parent does not want to know), testing of twins, and other family issues related to tests. Some of these discussions focus on the ethical principles involved, and others focus more on the clinical outcomes (see Tables V and VI, respectively). Other ethical challenges for clinical practitioners include anonymous testing, counseling of patients and family members when an affected person learns he or she is unexpectedly homozygous (or, more likely, compound heterozygous) for an expanded CAG repeat, and counseling regarding expansions and contractions in and across the intermediate CAG repeat boundaries…
One of the most dramatic societal changes since John Pearson proposed a treatment model emphasizing genetic counseling in 1955 is the immediate availability of information to anyone with Internet access. This information access may make us feel more autonomous and more in control of our lives, but information without context is commonly forgotten, misinterpreted, or entirely misunderstood.
We recall a recent referral to our center of an at-risk patient who had previously obtained predictive testing through a local physician and was told that “the HD gene is normal.” Subsequent review by a genetics professional 3 years—and two pregnancies—later showed that although the patient's first allele (described on the first page of the laboratory report) was normal, the second allele (described on the next page of the report) had a CAG repeat expansion. Apparently the report that the physician saw was missing a page, but neither the physician nor the patient thought to make sure that they saw results for both alleles, even though both had likely learned in the past that humans have two copies of each gene.
Cases like this one emphasize the importance of one-on-one genetic counseling to ensure that patients have the knowledge base to understand their results. Despite the widespread availability of information about the genetics of HD on the Internet and in books, textbooks, videos, and many other media, we routinely see patients, students, and physicians who fail to understand basic concepts. Counseling sessions allow genetics experts to emphasize or review certain points or to rephrase their descriptions of concepts to match the particular levels of education and medical sophistication of their patients. Such sessions also provide a context for information to be retained; attending a seminar at an HD conference about predictive testing is not nearly as valuable for patients as discussing their particular reasons for considering predictive testing with a genetic counselor…
If the goal is to get more people tested, then we could assess quality by looking at the proportion of patients counseled by a particular counselor who subsequently undergo testing. If there is a sense that we should strive to reduce the total burden of HD in the next generation through counseling and educational activities, as Dr. Pearson (1955) advocated 60 years ago, then the current approach to genetic counseling and testing is not succeeding. In fact, a very recent study has documented a dramatic increase in the prevalence of HD in Northern England between 1990 and 2010; the estimated prevalence of HD there has risen from 5.4/100,000 (95% CI 3.8–7.5) in 1990 to 12.3 (11.2–13.5)/100,000 in 2010 [Bargiela et al., 2015]. Although this is likely due in large part to improved ascertainment of the disorder in older individuals with a vague or absent family history, it does not appear that the availability of genetic counseling, predictive testing, or prenatal or preimplantation testing has led to any reduction in the prevalence of the disease. And if the goals are to provide information (recalled or not) that allows people to make the right decisions for themselves about whether to have a predictive, prenatal, or preimplantation test, then perhaps we are succeeding, at least with the patients that we are reaching. Future researchers should work to develop metrics to evaluate the success of one counseling approach over another in this regard.
Another problem for the future is the potential necessity to upscale genetic testing services to meet what could be a significant influx of requests for testing from at-risk applicants who need a positive gene test result in order to qualify for a research study of a putative disease-modifying treatment. Phase 1 trials of gene-silencing therapy in HD have begun, and as this and other treatments move into larger clinical trials, this may change the perceived potential rewards of the gene test. Genetic service providers need to be aware as such trials become available, as patients who seek predictive tests so that they can get into research studies may be unprepared for the uncertainty and potential disappointment that may accompany a test result, and then they may be disappointed again if for some reason they are unable to participate in the research study.
The cornerstone of the genetic management of HD remains genetic counseling. In the 1950s, Reed rejected the terms “genetic consultation,” “genetic advice,” and “genetic hygiene” in favor of the term “genetic counseling,” and that term remains apt today [Holtan, 2011]. Neither genetic counseling, available since the 1950s, nor accurate genetic testing, available since 1993, have reduced the prevalence of HD. Indeed, most genetics practitioners would agree that a “public health” goal, such as a reduction in the prevalence of the disease, should not be in our minds as we counsel individual patients and families. It seems, then, that the goal of genetic care in HD should be to provide accurate information to individual patients at the correct time, in a supportive environment, and in a context that is relevant to their lives, while simultaneously navigating the thorny challenges of the family, which is truly the unit of care in genetic medicine. Reaching a broader pool of families and determining which aspects of, or approaches to, genetic counseling are associated with high-quality care are the key challenges for the future.