Changes in screening behaviors and attitudes toward screening from pre‐test genetic counseling to post‐disclosure in Lynch syndrome families

The purpose of this study was to examine colonoscopy adherence and attitudes toward colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer‐unaffected relatives of Lynch syndrome mutation carriers before pre‐test genetic counseling (baseline) and at 6 and 12 months post‐disclosure of test results (52 mutation negative and 26 mutation positive). While both groups were similar at baseline, at 12 months post‐disclosure, a greater number of mutation‐positive individuals had had a colonoscopy compared with mutation‐negative individuals. From baseline to 12 months post‐disclosure, the mutation‐positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self‐efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation‐negative group. To conclude, adherence to risk‐appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation‐positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence.     

Attitudinal concordance toward uptake and disclosure of genetic testing for cancer susceptibility in patient–family member dyads

Decisions for cancer susceptibility genetic testing (CSGT) uptake and dissemination of results occur within the family context. A national survey was performed with 990 patient–family member dyads (participation rate:76.2%), with paired questionnaires examining attitudes toward CSGT uptake and disclosure of results in response to a hypothetical scenario in which a reliable CSGT was available for the specific cancer a patient was being treated. While most patients and family members responded they would uptake or recommend CSGT if available, concordance between the dyads was poor for both patient's testing (agreement rate 77.5%, weighted κ = 0.09) and first‐degree relatives' testing(agreement rate 78.0%, weighted κ = 0.09). Most patients (93.2%) and family members (92.9%) indicated that patients should disclose positive CSGT results to family members, with dyadic agreement of 89.1% (κ = 0.15). However, there were substantial disagreement regarding when disclosure should take place, who should make the disclosure (the patient or the health care professionals), and to whom the results should be disclosed. Patients and family members may hold different attitudes toward CSGT uptake of and disclosure of results within the family. Our findings reinforce the need for a family system approach to incorporate perspectives of patients as well as their family members.     

Ethical issues in susceptibility genetic testing for late‐onset neurodegenerative diseases

Genome‐wide association studies have revolutionized our understanding of the genetic architecture of complex traits and diseases over the last decade. This knowledge is enabling clinicians, researchers, and direct‐to‐consumer genetics companies to conduct disease susceptibility testing based on powerful methods such as polygenic risk scoring. However, these technologies raise a set of complex ethical, legal, social, and policy considerations. Here we review and discuss a series of ethical dilemmas associated with susceptibility genetic testing for the two most common late‐onset neurodegenerative diseases, Alzheimer's and Parkinson's disease, including testing in asymptomatic individuals. Among others, these include informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. Importantly, appropriate counseling is a deciding factor for the ethical soundness of genetic testing, which poses a challenge for the regulation of these tests and the training of healthcare professionals. As genetic knowledge about these diseases continues growing and genetic testing becomes more widespread, it is increasingly important to raise awareness among researchers, medical practitioners, genetic counselors, and decision makers about the ethical, legal, and social issues associated with genetic testing for polygenic diseases.     

‘Information is information’: a public perspective on incidental findings in clinical and research genome‐based testing

The potential for genomic incidental findings is increasing with the use of genome‐based testing. At the same time approaches to clinical decision making are shifting to shared decision‐making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross‐section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome‐based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.     

The communication of secondary variants: interviews with parents whose children have undergone array‐CGH testing

Children with unexplained developmental disabilities or congenital anomalies are increasingly being referred for genetic diagnostic testing using array‐comparative genomic hybridisation (array‐CGH) and next‐generation sequencing (NGS) technologies. Their parents will have to deal with the secondary variants that will inevitably arise. We conducted 16 prospective semi‐structured interviews with native Dutch‐speaking parents whose children had undergone clinical array‐CGH testing. The interviews explored the parents' experiences, expectations and opinions, specifically regarding the communication of results. Concrete examples of ‘unexpected results’ were provided to help guide the discussion, differing in severity, treatability, time of onset, level of risk, and carrier status. Data was analysed using content and narrative analysis methodologies. Parental motivations for and against the disclosure of unexpected results cluster around four main themes: actionability; knowledge; context; and characteristics of the result. Most parents wished to know all types of results. Disclosure was framed within a holistic, contextual, family‐wide view. Genetic counselling should aim to integrate explorations of the motivations of parents surrounding the disclosure of results with good clinical care.     

Attitudes toward the genetic testing of children among adults in a Utah‐based kindred tested for a BRCA1 mutation

Advances in molecular biology and genetics have led to the identification of the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2, along with tests to detect mutations in these genes. Although the appropriateness of BRCA1/2 genetic testing for children has been debated in the literature, little is known about the attitudes of individuals who have undergone cancer susceptibility testing. The present study focused on attitudes toward BRCA1 testing for children among 218 adults from a Utah‐based kindred who had received BRCA1 test results. Results indicated that approximately one‐fourth of the participants would permit BRCA1 testing for children under the age of 18. General attitudes about genetic testing were predictive of attitudes toward the testing of children. In addition, men and individuals without a BRCA1 mutation were more likely to agree that minors should be allowed BRCA1 testing. Individuals whose mother had been affected with breast cancer were less likely to permit testing for minors. Among parents of minor children, less than one‐fifth indicated that they would want BRCA1 testing for their own children; carrier status was not predictive of attitudes toward testing their own children. As breast/ovarian cancer susceptibility testing continues to be disseminated into clinical settings, there may be an increase in the number of test requests for minors. The findings of the present study represent an important step in exploring attitudes about genetic testing of children among individuals who have received cancer susceptibility test results. Am. J. Med. Genet. 92:25–32, 2000. © 2000 Wiley‐Liss, Inc.     

Availability of treatment drives decisions of genetic health professionals about disclosure of incidental findings

Contrasting opinions exist regarding the disclosure of incidental findings detected through clinical genomic testing. This study used a discrete choice experiment to investigate genetic health professionals'' preferences for the disclosure of incidental findings in an Australian paediatric setting. Four attributes of conditions relating to incidental findings were investigated: availability of prevention and treatment, chance of symptoms ever developing, age of onset and severity. Questionnaires from 59 Australian genetic health professionals were analysed. Results show that when evaluating incidental findings for disclosure, these professionals value the availability of prevention and treatment for the condition above all other characteristics included in the study. The framework of this discrete choice experiment can be used to investigate the preferences of other stakeholders such as paediatricians and parents about disclosure of incidental findings. The results of this study may be considered when assessing which categories of incidental findings are most suitable for disclosure in clinical practice.     

Preferences for results from genomic microarrays: comparing parents and health care providers

Chromosomal microarray (CMA) testing is now performed frequently in paediatric care. Although CMAs improve diagnostic yields, they increase detection of variants of unknown and uncertain clinical significance (VUS). Understanding parents', paediatricians' and genetic health professionals' (GHPs) views regarding variant disclosure may reduce the potential for communication of unwanted information. A questionnaire was designed to compare disclosure preferences of these three groups in Australia. One hundred and forty‐seven parents, 159 paediatricians and 69 GHPs hold similar views with at least 89% of respondents certainly or probably favouring disclosure of all categories of variants. However, some differences were observed between health care providers (HCPs: paediatricians and GHPs) and parents, who were less sure of their disclosure preferences. There was consensus among respondent groups that knowledge of a variant of certain clinical significance would provide more practical and emotional utility compared to VUS. Compared to HCPs, parents placed more emphasis on using knowledge of a VUS when considering future pregnancies (p < 0.001). This study may help HCPs anticipate parents' preferences for genomic testing. As whole exome/genome sequencing is integrated into clinical practice, the potential for differing views of parents and HCPs should be considered when developing guidelines for result disclosure.     

‘It had to be done’: genetic testing decisions for arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disease of the heart muscle, causing life‐threatening ventricular arrhythmias, sudden cardiac death and/or biventricular heart failure. Little research examines ARVC genetic test decisions, despite the gravity of the condition. This qualitative study used semi‐structured interviews to explore the testing decisions of 21 individuals across 15 families segregating a well‐studied, particularly lethal form of ARVC caused by a p.S358L TMEM43 mutation. Genetic testing decisions were rarely described as ‘decisions’ per se, but rather ‘something that had to be done’. This perception was attributed to personality type or personal suspicion of carrying the TMEM43 mutation, but most often was described in the context of testing for other family members, usually children. Participants related a strong need to rule out risk, more for children than for themselves, but lingering doubts remained about personal and children's risk for ARVC, even when gene test results were negative. Study findings highlight the interdependent nature of genetic test decisions and suggest that an individualistic conception of autonomy in genetic services may not meet the needs of affected families. Findings also suggest the need for follow‐up support of families affected by ARVC, including for those individuals testing negative for the family mutation.     

Parental attitudes,values, and beliefs toward the return of results from exome sequencing in children

Exome sequencing is being offered for children with undiagnosed conditions to identify a primary (causative) variant. Parental preferences for learning secondary (incidental) variants are largely unexplored. Our objective was to characterize values and beliefs that shape parents' preferences for learning their children's sequencing results. We conducted semi‐structured interviews with 25 parents of 13 minor probands with a variety of rare genetic conditions. Parents were asked to discuss their preferences to receive four types of results from exome sequencing. Many parents preferred to receive all types of results. Parents had the most positive attitudes toward learning about variants that predispose to disorders treatable or preventable in childhood. They had reservations about learning about predispositions for untreatable adult‐onset conditions and carrier status for recessive conditions. Parents described their success in coping with their child's condition as evidence for an ability to manage any additional negative health information. They felt responsible for learning about secondary variants, desiring a gain in control over their child's health. Our findings suggest that investigators should incorporate parents' perceptions of the value in receiving secondary variant information about their children when designing studies employing exome sequencing.     

Decision‐making for non‐invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self‐determination, independence, and self‐sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non‐invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi‐structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision‐making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision‐making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision‐making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.     

To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts

Any test that produces visual images or digital or genetic sequences will tend to produce incidental findings because more will be visible than what was originally sought. We conducted a systematic review of the ethical reasons presented in the literature for and against the disclosure of incidental findings arising in clinical and research genetics contexts. A search of electronic databases resulted in 13 articles included for systematic review. Articles presented reasons for and against disclosure, and reasons for proceeding with caution when making decisions about disclosure. One major recommendation of the reviewed articles is in favor of qualified disclosure: incidental findings with confirmed clinical utility where there is the possibility of treatment or prevention should be disclosed, with exceptions. A second type of recommendation is that disclosure should proceed with caution, especially in the context of new genetic technologies and genetic testing involving minors. It is also recommended that the number of possible incidental findings be limited even before genetic testing is carried out. Such a policy, which we advocate, would show preference for non-disclosure.     

Genetics in democratic societies - the Nordic perspective

This report, with its emphasis on consensus points in the deliberations of the First Bioethics Workshop under the auspices of the Nordic Genome Initiative (an activity under the Nordic Council through its Nordic Programme Committee for Biotechnology), presents a Nordic perspective on the international discussion of ethical and legal issues relating to genetic testing. The Nordic countries have important common denominators with respect to political structure, education, religion, languages, cultural traditions and attitudes towards human values. A comprehensive national health service exists in all Nordic countries and there are important common legal foundations with great similarities between countries. However, in areas related to biotechnology there are considerable legal differences, but these differences do not necessarily reflect differences in underlying principles. Important ethical principles relevant to genetic testing that are shared by the Nordic countries include the concept of social justice with great stress on equality of treatment, the right to autonomy, the right to full disclosure of test results, strict confidentiality with respect to test resulis, the requirement that participation in testing programs must always be voluntary and based on information, and a responsible balance between risks or inconveniences on one hand and benefits on the other.     

Sudden death: ethical and legal problems of post‐mortem forensic genetic testing for hereditary cardiac diseases

Elger BS, Michaud K, Fellmann F, Mangin P. Sudden death: ethical and legal problems of post‐mortem forensic genetic testing for hereditary cardiac diseases. Hereditary non‐structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young. In these cases, genetic testing can be useful and does not require proxy consent if it is carried out at the request of judicial authorities as part of a forensic death investigation. Mutations in several genes are implicated in arrhythmic syndromes, including SCN5A, KCNQ1, KCNH2, RyR2, and genes causing HCM. If the victim's test is positive, this information is important for relatives who might be themselves at risk of carrying the disease‐causing mutation. There is no consensus about how professionals should proceed in this context. This article discusses the ethical and legal arguments in favour of and against three options: genetic testing of the deceased victim only; counselling of relatives before testing the victim; counselling restricted to relatives of victims who tested positive for mutations of serious and preventable diseases. Legal cases are mentioned that pertain to the duty of geneticists and other physicians to warn relatives. Although the claim for a legal duty is tenuous, recent publications and guidelines suggest that geneticists and others involved in the multidisciplinary approach of sudden death (SD) cases may, nevertheless, have an ethical duty to inform relatives of SD victims. Several practical problems remain pertaining to the costs of testing, the counselling and to the need to obtain permission of judicial authorities.     

Attitudes of Dutch general practitioners towards presymptomatic DNA-testing for Huntington disease

The attitudes of 1020 Dutch GP's towards presymptomatic and prenatal testing for Huntington disease (HD) were studied by means of a postal questionnaire. The questionnaire contained questions about: approval of presymptomatic DNA-testing, informing individuals at-risk who do not request predictive testing, referral to a clinical genetics center, and opinions about different strategies of informing and supporting individuals at-risk. The response rate was 62%. More than two-thirds of the GP's considered post-test counselling and support as their responsibility. Twenty-six per cent were of the opinion that the test results should be disclosed by the GP. Fifty-nine per cent of GP's who had an individual at-risk in their practice were familiar with the test. The attitudes of GP's towards giving support and giving test results were independent of familiarity with the test and the incidence of HD-patients or at-risk individuals in the practice. Although GP's were willing to play an important role in presymptomatic DNA-testing procedures, there is a risk that they might underestimate the difficulties in communicating genetic information and the psychosocial effects of DNA-testing. Hence, we favor the premise that extensive pretest counselling and test disclosure should remain the prime responsibility of the clinical geneticist. Increasing involvement of GP's should, however, be encouraged and combined with appropriate postgraduate education about predictive DNA-testing in general.     

Psychosocial implications of living with familial risk of a psychiatric disorder and attitudes to psychiatric genetic testing: A systematic review of the literature

The aim of this systematic review was to synthesize the existing evidence documenting the psychosocial implications of living with a familial risk of an adult‐onset psychiatric disorder. Six databases were searched systematically to identify qualitative and quantitative studies, which explored perspectives of those at increased risk for psychiatric disorders, as well as the general public. Thematic analysis was used to identify major themes. Thirty‐five articles met the eligibility criteria and reported on the views of 4,896 participants. The literature demonstrates strong interest in psychiatric genetic testing of adults as well as children, whereas attitudes toward prenatal testing were much less positive. Predictors of interest in testing, as well as perceived advantages and disadvantages were identified. Very few studies are available on anticipated and actual reactions to receiving results. Studies show that the majority of participants feel that having a genetic explanation would alleviate some of the stigma associated with mental illness. This review shows that interest in, and predictors of attitudes toward, psychiatric genetic testing are well researched, but the extent to which attitudes will translate into actual testing uptake is unknown. Future research also needs to assess the actual behavioral and psychological impact of genetic testing.     

Psychiatrists' attitudes,knowledge, and experience regarding genetics: a preliminary study

PurposeThis study is the first survey of a random national sample of US psychiatrists to assess attitudes, knowledge, and clinical experience regarding genetics. We hypothesized that clinicians with more recent genetics training would demonstrate more positive attitudes and greater genetics knowledge and experience than those with less recent training.MethodsA probability sample of US psychiatrists (n = 93) was invited to participate in a mail survey regarding genetic medicine.ResultsForty-five psychiatrists completed the survey (response rate = 48%). All believed that genetics strongly or moderately influenced a person's mental health. Respondents expressed positive attitudes toward incorporating genetics into psychiatric practice, but most did not have recent genetics training or experience in referring patients to genetic counselors or ordering genetic tests. Psychiatrists who had genetics training within the previous 5 years had more experience in providing genetic services.ConclusionsThis survey identified areas of strength (positive attitudes about providing genetic services, belief in the heritability of mental illness) and future targets for educational intervention (general genetics, information about testing and counseling resources). The association between recent training and a greater level of clinical genetics experience suggests that educational efforts may be successful in preparing psychiatrists to provide genetic services in the future.     

Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure

Battistuzzi L, Ciliberti R, Forzano F, De Stefano F. Regulating the communication of genetic risk information: the Italian legal approach to questions of confidentiality and disclosure. Communication of genetic risk is a complex process in which the rights of the individual and those of relatives may conflict with regard to the information revealed by DNA testing. If patients who participate in clinical genetic testing refuse to share their genetic information with at-risk relatives, healthcare professionals need to reach a proper ethical balance between the right of individual patients regarding the confidentiality of their genetic test result and the right of families to be informed about their genetic risk. Rules and legislation in most countries generally protect the confidentiality of medical information but allow limited disclosure of genetic test results without the patient's consent in specific cases when certain conditions are met. The aim of this article is to draw attention to how Italian policymakers have attempted to balance protection of autonomy and confidentiality, and protection of health by means of a hybrid instrument. Furthermore, we show that some of the requirements of that instrument depart from the most widely recognized standards for non-consensual disclosure of genetic risk information, while at the same time allowing an unusually high level of discretion to healthcare professionals involved in genetic counseling and testing.     

German Ethics Council on genetic diagnostics: trend setting?

On 30 April 2013, the German Ethics Council (‘Council'') published its opinion on ‘The future of genetic diagnostics—from research to clinical application'' (‘the Opinion''). The Council was asked by the German government to discuss the future of genetic diagnostic methods in relation to the current applicable laws and regulations as well as the ethical stand points. The Council''s 23 recommendations show that the existing regulations in Germany, and indirectly on a European level, lack in protecting consumers sufficiently. Consumer protection built the major focus of the Council''s opinion. However, the opinion misses a critical overall analysis of genetic testing and, for example, the potential misuse of genetic test results by insures or the risk of disclosure toward employers. The Council missed an opportunity to discuss which barriers are necessary from a legal and ethical perspective but which still do not prohibit genetic testing and research.     

Sib understanding of genetics and attitudes toward carrier testing for X‐linked severe combined immunodeficiency

X‐linked severe combined immunodeficiency (XSCID) is the most common genetic form of SCID, a rare disease with profoundly impaired immunity. SCID was previously fatal but now can be treated by bone marrow transplantation. Mapping of XSCID in 1985 and identification of the disease gene, IL2RG, in 1993 made possible patient and carrier diagnosis. We assessed understanding of the genetics of XSCID in adult sibs recruited from families in which a proband had enrolled in our protocols and had attended an XSCID family workshop. Thirty‐seven female and three male sibs completed a questionnaire and semistructured interview. Overall knowledge of genetics of XSCID was excellent. An overwhelming majority of participants (93%) believed that daughters should be tested for XSCID carrier status; 89% would prefer to have their own daughter tested prior to age 18 years (M = 9, median = 12), and 34% would test at birth. Moreover, 89% felt they would disclose carrier results to their daughter before adulthood (M = 12 years, median = 12); 51% would tell prior to adolescence. XSCID sibs were optimistic about medical science and assertive in their search for the latest information. Genetic information should be made available to families over time and should include discussion of reproductive risks for sons surviving with XSCID and daughters as they grow up. We recommend that genetic counseling for XSCID include children in age‐appropriate discussions and that counselors help parents weigh benefits of early testing and disclosure versus the potential harm of loss of child autonomy. Published 2001 Wiley‐Liss, Inc.