Impact of early preeclampsia prediction on medication adherence and behavior change: a survey of pregnant and recently-delivered individuals.

BACKGROUND: Behavior change and medication adherence represent potential barriers to optimal prevention of pregnancy complications including preeclampsia. We sought to evaluate baseline sentiments on pregnancy care and medication amenability, and how these measures would be impacted by early predictive testing for preeclampsia. METHODS: We developed a digital survey to query participants' baseline sentiments on pregnancy care, knowledge about pregnancy complications, and views on a hypothetical test to predict preeclampsia. The survey was administered online to pregnant and recently-delivered individuals in the United States. Survey data were analyzed using pooled two-sample proportion z-tests with adjustment for multiple comparisons. RESULTS: One thousand and twenty-two people completed the survey. 84% reported they were satisfied with their pregnancy care. Self-assessed knowledge about preeclampsia was high, with 75% of respondents reporting they have a "good understanding" of preeclampsia, but measured knowledge was low, with only 10% able to identify five common signs/symptoms of preeclampsia. Notably, 40% of participants with prior preeclampsia believed they were at average or below-average risk for recurrence. 91% of participants desired early pregnancy predictive testing for preeclampsia. If found to be at high risk for preeclampsia, 88% reported they would be more motivated to follow their provider's medication recommendations and 94% reported they would desire home blood pressure monitoring. Increased motivation to follow clinicians' medication and monitoring recommendations was observed across the full spectrum of medication amenability. Individuals who are more medication-hesitant still reported high rates of motivation to change behavior and adhere to medication recommendations if predictive testing showed a high risk of preeclampsia. Importantly, a high proportion of medication-hesitant individuals reported that if a predictive test demonstrated they were at high risk of preeclampsia, they would feel more motivated to take medications (83.0%) and aspirin (75.9%) if recommended. CONCLUSION: While satisfaction with care is high, participants desire more information about their pregnancy health, would value predictive testing for preeclampsia, and report they would act on this information. Improved detection of at-risk individuals through objective testing combined with increased adherence to their recommended care plan may be an important step to remedy the growing gap in prevention.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

This Position Statement provides guidelines for health professionals who work with individuals and families seeking predictive genetic testing and laboratory staff conducting the tests. It presents the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity, and adults living with reduced or fluctuating cognitive capacity.Predictive Testing Recommendations: (1) Predictive testing in adults, young people and children should only be offered with pretest genetic counseling, and the option of post-test genetic counseling. (2) An individual considering whether to have a predictive test should be supported to make an autonomous and informed decision. Regarding Children and Young People: (1) Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies, or other medical interventions in the immediate future. (2) Where symptoms are likely to develop in childhood, in the absence of direct medical benefit from this knowledge, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. (3) Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make an autonomous and informed decision. This is applicable regardless of whether there is some action that can be taken in adulthood.

Does a proactive procedure lead to a higher uptake of predictive testing in families with a pathogenic BRCA1/BRCA2 variant? A family cancer clinic evaluation.

The uptake of genetic counseling and predictive genetic testing by family members at risk for hereditary tumor syndromes is generally below 50%. To address this issue, a new guideline was introduced in the Netherlands in 2019 that aims to improve the sharing of information within families. In addition to cascade screening supported by follow-up telephone calls with the proband, municipal records were accessed to allow the geneticist to contact at-risk family members directly. We evaluated this procedure in 32 families with a (likely) pathogenic germline BRCA1/BRCA2 variant diagnosed at our hospital between May 1, 2020, and July 31, 2021, comparing current uptake with outcomes achieved for 33 families diagnosed in 2014. Fifteen months after diagnostic testing of the proband, the uptake was 43% (120/277), comparable to the 44% (87/200) registered previously. Among a subgroup of women at 50% risk aged 25-75 years, 71% (47/66) were tested, comparable to an earlier uptake of 69% (59/86). Of the 34 at-risk relatives we contacted directly, 17 (50%) underwent predictive testing. In conclusion, we found no evidence that the new procedure leads to a substantially increased uptake. Future research should be primarily aimed at understanding intrafamilial communication barriers.

Diagnostic and predictive accuracy of anti-mullerian hormone for ovarian function after chemotherapy in premenopausal women with early breast cancer.

PURPOSE: Accurate diagnosis and prediction of loss of ovarian function after chemotherapy for premenopausal women with early breast cancer (eBC) is important for future fertility and clinical decisions regarding the need for subsequent adjuvant ovarian suppression. We have investigated the value of anti-mullerian hormone (AMH) as serum biomarker for this. METHODS: AMH was measured in serial blood samples from 206 premenopausal women aged 40-45 years with eBC, before and at intervals after chemotherapy. The diagnostic accuracy of AMH for loss of ovarian function at 30 months after chemotherapy and the predictive value for that of AMH measurement at 6 months were analysed. RESULTS: Undetectable AMH showed a high diagnostic accuracy for absent ovarian function at 30 months with AUROC 0.89 (96% CI 0.84-0.94, P < 0.0001). PPV of undetectable AMH at 6 months for a menopausal estradiol level at 30 months was 0.77. In multivariate analysis age, pre-treatment AMH and FSH, and taxane treatment were significant predictors, and combined with AMH at 6 months, gave AUROC of 0.90 (95% CI 0.86-0.94), with PPV 0.79 for loss of ovarian function at 30 months. Validation by random forest models with 30% data retained gave similar results. CONCLUSIONS: AMH is a reliable diagnostic test for lack of ovarian function after chemotherapy in women aged 40-45 with eBC. Early analysis of AMH after chemotherapy allows identification of women who will not recover ovarian function with good accuracy. These analyses will help inform treatment decisions regarding adjuvant endocrine therapy in women who were premenopausal before starting chemotherapy.

Predictors of interest in predictive testing for rheumatoid arthritis among first degree relatives of rheumatoid arthritis patients.

OBJECTIVES: There is increasing interest in prediction and prevention of RA. It is important to understand the views of those at risk to inform the development of effective approaches. First-degree relatives (FDRs) of RA patients are at increased risk of RA. This study assessed predictors of their interest in predictive testing for RA. METHODS: Questionnaires were completed by RA patients (provided with their questionnaire by a healthcare professional) and their FDRs (provided with their questionnaire by their RA proband). FDR surveys assessed interest in taking a predictive test, demographic variables, perceived RA risk, attitudes about predictive testing, autonomy preferences, illness perceptions, avoidance coping and health anxiety. Patient surveys included demographic variables, disease impact, RA duration and treatment. Ordinal logistic regression examined the association between FDRs' characteristics and their interest in predictive testing. Generalized estimating equations assessed associations between patient characteristics and FDRs' interest in predictive testing. RESULTS: Three hundred and ninety-six FDRs responded. Paired data from the RA proband were available for 292. The proportion of FDRs interested in predictive testing was 91.3%. Information-seeking preferences, beliefs that predictive testing can increase empowerment over health and positive attitudes about risk knowledge were associated with increased interest. Beliefs that predictive testing could cause psychological harm predicted lower interest. Patient characteristics of the proband were not associated with FDRs' interest. CONCLUSIONS: FDRs' interest in predictive testing for RA was high, and factors associated with interest were identified. These findings will inform the development of predictive strategies and informational resources for those at risk.

How to build a game for empirical bioethics research: The case of 'Tracing Tomorrow'.

It is becoming increasingly clear that the field of empirical bioethics requires methodological innovations that can keep up with the scale and pace of contemporary research in health and medicine. With that in mind, we have recently argued for Design Bioethics-the use of purpose-built, engineered research tools that allow researchers to investigate moral decision-making in ways that are embodied and contextualized. In this paper, we outline the development, testing and implementation of a novel prototype tool in the Design Bioethics Workshop-with each step illustrated with collected data. Titled 'Tracing Tomorrow' (www.tracingtomorrow.org), the tool is a narrative game to investigate young people's values and preferences in the context of digital phenotyping for mental health. The process involved (1) Working with young people to discover, validate and define the morally relevant cases or problems, (2) Building and testing the game concept in collaboration with relevant groups and game developers, (3) Developing prototypes that were tested and iterated in partnership with groups of young people and game developers and (4) Disseminating the game to young people to collect data to investigate research questions. We argue that Design Bioethics yields tools that are relevant, representative and meaningful to target populations and provide improved data for bioethics analysis. PATIENT OR PUBLIC CONTRIBUTION: In planning and conducting this study, we consulted with young people from a diverse range of backgrounds, including the NeurOX Young People's Advisory Group, the What Lies Ahead Junior Researchers Team, Censuswide youth participants and young people from the Livity Youth Network.

Acceptability of predictive testing for ischemic heart disease in those with a family history and the impact of results on behavioural intention and behaviour change: a systematic review.

BACKGROUND: Tests to predict the development of chronic diseases in those with a family history of the disease are becoming increasingly available and can identify those who may benefit most from preventive interventions. It is important to understand the acceptability of these predictive approaches to inform the development of tools to support decision making. Whilst data are lacking for many diseases, data are available for ischemic heart disease (IHD). Therefore, this study investigates the willingness of those with a family history of IHD to take a predictive test, and the effect of the test results on risk-related behaviours. METHOD: Medline, EMBASE, PsycINFO, LILACS and grey literature were searched. Primary research, including adult participants with a family history of IHD, and assessing a predictive test were included. Qualitative and quantitative outcomes measuring willingness to take a predictive test and the effect of test results on risk-related behaviours were also included. Data concerning study aims, participants, design, predictive test, intervention and findings were extracted. Study quality was assessed using the Standard Quality Assessment Criteria for Evaluating Research Papers from a Variety of Fields and a narrative synthesis undertaken. RESULTS: Five quantitative and two qualitative studies were included. These were conducted in the Netherlands (n = 1), Australia (n = 1), USA (n = 1) and the UK (n = 4). Methodological quality ranged from moderate to good. Three studies found that most relatives were willing to take a predictive test, reporting family history (n = 2) and general practitioner (GP) recommendation (n = 1) as determinants of interest. Studies assessing the effect of test results on behavioural intentions (n = 2) found increased intentions to engage in physical activity and smoking cessation, but not healthy eating in those at increased risk of developing IHD. In studies examining actual behaviour change (n = 2) most participants reported engaging in at least one preventive behaviour, particularly medication adherence. CONCLUSION: The results suggests that predictive approaches are acceptable to those with a family history of IHD and have a positive impact on health behaviours. Further studies are needed to provide a comprehensive understanding of predictive approaches in IHD and other chronic conditions.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

In 2020, the Human Genetics Society of Australasia released its Position Statement on Predictive and Presymptomatic Genetic Testing in Adults and Children. This Position Statement synthesizes the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity and adults living with reduced or fluctuating capacity. Recommendations include that predictive testing in adults, young people and children should only be offered with pretest genetic counseling and the option of posttest genetic counseling. An individual considering (for themselves or on behalf of another) whether to have a predictive test should also be supported to allow them to make an autonomous and informed decision. Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies or other medical interventions in the immediate future. Where symptoms are likely to develop in childhood, in the absence of options to implement surveillance or risk reduction measures, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make their own autonomous and informed decision.

Giving adolescents a voice: the types of genetic information adolescents choose to learn and why.

PURPOSE: The American College of Medical Genetics and Genomics supports parents' opting in or out of secondary analysis of 59 genes when their child has clinical exome/genome sequencing. We explored the reasons adolescents choose to learn certain types of results and the reasons they want to involve or not involve parents in decision-making. METHODS: Adolescents recruited without clinical indication were offered independent, followed by joint choices with a parent to learn genomic results. After making independent choices, adolescent/parent dyads were interviewed to explore the reasons for their choices. Interviews were audio-recorded and transcribed. The constant comparative method was used to analyze 64 purposefully selected transcripts that included 31 from adolescents who excluded some or all potential results. RESULTS: Three major themes informed adolescents' choices: (1) actionability of information, (2) knowledge seeking, and (3) psychological impact. Of adolescents who independently excluded some conditions (n=31), 58% changed their initial choices during the joint interview due to parental influence or improved understanding. Nearly all adolescents (98%) wanted to be involved in the decision-making process, and 53% wanted to make choices independently. CONCLUSIONS: Our findings contribute empirical evidence to support the refinement of professional guidelines for adolescents' engagement and preferences in genetic testing decisions.

What to Do with a Second Chance in Life? Long-Term Experiences of Non-carriers of Huntington's Disease.

Little is known about how people's lives are influenced when going from a 50% risk status of Huntington's disease (HD) to no risk after performing predictive testing. In this study, 20 interviews were conducted to explore the long-term (> 5 years) experiences after receiving predictive test results as a non-carrier of HD. The results showed a broad variety of both positive and negative reactions. The most prominent positive reaction reported was feelings of relief and gratitude, of not carrying the HD mutation for themselves and for their children. Also, the non-carrier status promoted in some individuals' significant life changes such as a wishing to have (more) children, pursuing a career or breaking up from an unhappy relationship. However, negative reactions on their psychological well-being were also described. Some had experienced psychological pressure of needing to do something extraordinary in their lives; others expressed feelings of guilt towards affected or untested siblings, resulting in sadness or clinical depression. The new genetic risk status could generate a need of re-orientation, a process that for some persons took several years to accomplish. The results of the present study show the importance of offering long-term post-result counselling for non-carriers in order to deal with the psychological consequences that may follow predictive testing.

Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease, affecting the upper and/or lower motor neurons. However, extramotor symptoms can also occur; cognitive deficits are present in more than 40% of patients and 5-8% of ALS patients develop frontotemporal dementia. There is no effective treatment for ALS and median survival is 2-3 years after onset. Amyotrophic lateral sclerosis is a genetically heterogeneous disorder with monogenic forms as well as complex genetic etiology. Currently, complex genetic risk factors are of minor interest for routine diagnostic testing or counseling of patients and their families. By contrast, a monogenic cause can be identified in 70% of familial and 10% of sporadic ALS cases. The most frequent genetic cause is a noncoding hexanucleotide repeat expansion in the C9orf72 gene. In recent years, high-throughput sequencing technologies have helped to identify additional monogenic and complex risk factors of ALS. Genetic counseling should be offered to all ALS patients and their first- and possibly second-degree relatives, and should include information about the possibilities and limitations of genetic testing. Routine diagnostic testing should at least encompass the most frequently mutated disease genes (C9orf72, SOD1, TDP-43, FUS). Targeted sequencing approaches including further disease genes may be applied. Caution is warranted as the C9orf72 repeat expansion cannot be detected by routine sequencing technologies and testing by polymerase chain reaction (PCR) is failure-prone. Predictive testing is possible in families in which a genetic cause has been identified, but the limitations of genetic testing (i. e., the problems of incomplete penetrance, variable expressivity and possible oligogenic inheritance) have to be explained to the families.

Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.

Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a single intestinal medium, FaSSIF, to simulate release in the small intestine, and a "transfer" (two-stage) protocol to simulate the concentration profile when conditions are changed from the gastric to the intestinal environment. The test products chosen were commercially available ibuprofen tablets and zafirlukast tablets. The biorelevant dissolution tests showed a high degree of reproducibility among the participating laboratories, even though several different batches of the commercially available medium preparation powder were used. Likewise, results were almost identicalbetween the commercial biorelevant media and those produced in-house. Comparing results to previous ring studies, including those performed with USP calibrator tablets or commercially available pharmaceutical products in a single medium, the results for the biorelevant studies were highly reproducible on an interlaboratory basis. Interlaboratory reproducibility with the two-stage test was also acceptable, although the variability was somewhat greater than with the single medium tests. Biorelevant dissolution testing is highly reproducible among laboratories and can be relied upon for cross-laboratory comparisons.

[Practical guidelines for genetic testing in cardiovascular diseases]. / Praktische Durchführung der genetischen Diagnostik in der Kardiologie.

In the last decade, genetic testing for cardiovascular disorders has become more and more relevant. Progress in molecular genetics has led to new opportunities for diagnostics, improved risk prediction and could lead to novel therapeutic approaches. Genetic diagnostic testing is relevant for both confirming a diagnosis as well as deciding on therapeutic consequences, if applicable. Furthermore, predictive testing in family members for specific cardiovascular diseases is now a standard procedure in holistic patient management. The process of genetic testing as well as documentation requirements and discussion of test results with patients are subject to legal regulations. These regulations might be confusing for clinical practitioners/cardiologists. The aim of this article is to provide a clinical framework for genetic testing. First, we explain the legal and ethical background. Second, we illustrate the process of genetic testing step by step and present updates on remuneration. Finally, we discuss the significance of genetic testing and specific disease indications in cardiology.

The Confluence of Psychiatric Symptoms and Neurodegenerative Disease: Impact on Genetic Counseling.

Hereditary neurodegenerative diseases can present with a psychiatric prodrome that overlaps with psychiatric symptoms that are not primary to these diseases. When individuals present for predictive testing while experiencing such symptoms, clinicians including genetic counselors, must proceed with caution and evaluate each situation on a case-by-case basis. Legitimate reasons may exist for moving forward with testing. Additionally predicting the consequences of testing is unrealistic so that the clinicians must do their best to prepare patients for both positive and negative results. A multidisciplinary team following the Huntington disease protocol remains the gold standard care for predictive testing for such patients. We discuss 3 case histories that demonstrate the complex nature of genetic counseling and testing in the presence of psychiatric symptoms, whether emanating from the disease itself or the results of living in an affected family.

Prospective Evaluation of Predictive DNA Testing for Huntington's Disease in a Large German Center.

We present a prospective study of counselees seeking predictive testing for Huntington's disease at the Huntington Center North Rhine-Westphalia (Bochum, Germany) between 2010 and 2012. The aim was to observe the decision-making process of at-risk individuals and explore their experiences following the decision as well as the impacts of positive and negative mutation results. Data were collected using two standardized questionnaires as well as via a semi-standardized telephone interview one year after the initial counseling session. Seventy-two  individuals participated in at least one of the three phases of the survey, including 31 individuals in the telephone interview. Sociodemographic data were in accordance with previous reports. The process of predictive testing was generally perceived in a positive manner, with almost all interviewees reporting a balanced emotional state one year after initial counseling, regardless of the decision for or against the test. The most important reasons named in favor of or against testing were assembled as well as different aspects regarding the satisfaction with the reached decision. In line with and expanding previous observations on gender-related differences in decision-making, our results suggest that gender-related aspects should be more strongly taken into account in genetic counseling during the predictive testing and counseling processes.

Genetic counseling and testing for Huntington's disease: A historical review.

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. © 2016 Wiley Periodicals, Inc.

Impact of Huntington Disease Gene-Positive Status on Pre-Symptomatic Young Adults and Recommendations for Genetic Counselors.

Huntington disease (HD) is an autosomal dominant, progressive neurodegenerative disorder for which there is no cure. Predictive testing for HD is available to asymptomatic at-risk individuals. Approximately half of the population undergoing predictive testing for HD consists of young adults (≤35 years old). Finishing one's education, starting a career, engaging in romantic relationships and becoming a parent are key milestones of young adulthood. We conducted a qualitative study to explore how testing gene-positive for HD influences young adults' attainment of these milestones, and to identify major challenges that pre-symptomatic young adults face to aid the development of targeted genetic counseling. Results of our study demonstrate that 1) knowing one's gene-positive status results in an urgency to reach milestones and positively changes young adults' approach to life; 2) testing positive influences young adults' education and career choices, romantic relationships, and family planning; 3) young adults desire flexible and tailored genetic counseling to address needs and concerns unique to this population. Findings of this study contribute to the understanding of the impact of predictive testing for HD on young adults, and highlight issues unique to this population that call for further research, intervention and advocacy.

Experiences of Women Who Underwent Predictive BRCA 1/2 Mutation Testing Before the Age of 30.

This qualitative interview study focuses on the experiences of a sample of British female BRCA 1/2 carriers who had predictive testing before the age of 30, which is the minimum age for breast screening in the UK. Following appropriate informed consent procedures participants were recruited through the Cancer Genetics Service for Wales. Semi-structured interviews were conducted face-to-face with seven participants, transcribed in full and analyzed using thematic analysis. The motives for testing and perceived advantages described by participants were similar to those identified in previous studies with older participants, such as increased awareness and knowledge and feeling more in control. However some of the perceived disadvantages were specific to younger women, including feeling pressured to make important life decisions earlier than they would have liked, such as about family planning and risk reducing surgery. Participants also reported feeling abandoned or forgotten because of lack of ongoing clinical contact, or feeling "stuck waiting" for screening to begin. However, none felt that these disadvantages were a reason to regret having testing. Findings in this small study suggest that having BRCA 1/2 predictive testing can have positive outcomes for young women even though they may be unable to access interventions such as breast screening. However it may be helpful to encourage young women during pre-test counseling to explore the decisions and choices they may face. These young women could benefit from ongoing support and follow up and increased interaction with healthcare professionals.

Rheumatoid arthritis patient perceptions on the value of predictive testing for treatments: a qualitative study.

BACKGROUND: Rheumatoid arthritis (RA) is a long term condition that requires early treatment to control symptoms and improve long-term outcomes. Lack of response to RA treatments is not only a waste of healthcare resources, but also causes disability and distress to patients. Identifying biomarkers predictive of treatment response offers an opportunity to improve clinical decisions about which treatment to recommend in patients and could ultimately lead to better patient outcomes. The aim of this study was to explore the understanding of and factors affecting Rheumatoid Arthritis (RA) patients' decisions around predictive treatment testing. METHODS: A qualitative study was conducted with a purposive sample of 16 patients with RA from three major UK cities. Four focus groups explored patient perceptions of the use of biomarker tests to predict response to treatments. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis by three researchers. RESULTS: Data were organised within three interlinking themes: [1] Perceptions of predictive tests and patient preference of tests; [2] Utility of the test to manage expectations; [3] The influence of the disease duration on take up of predictive testing. During consultations for predictive testing, patients felt they would need, first, careful explanations detailing the consequences of untreated RA and delayed treatment response and, second, support to balance the risks of tests, which might be invasive and/or only moderately accurate, with the potential benefits of better management of symptoms. CONCLUSIONS: This study provides important insights into predictive testing. Besides supporting clinical decision making, the development of predictive testing in RA is largely supported by patients. Developing strategies which communicate risk information about predictive testing effectively while reducing the psychological burden associated with this information will be essential to maximise uptake.

Ethical aspects of a predictive test for Huntington's Disease: A long term perspective.

BACKGROUND: A predictive genetic test for Huntington's disease can be used before any symptoms are apparent, but there is only sparse knowledge about the long-term consequences of a positive test result. Such knowledge is important in order to gain a deeper understanding of families' experiences. OBJECTIVES: The aim of the study was to describe a young couple's long-term experiences and the consequences of a predictive test for Huntington's disease. RESEARCH DESIGN: A descriptive case study design was used with a longitudinal narrative life history approach. PARTICIPANTS AND RESEARCH CONTEXT: The study was based on 18 interviews with a young couple, covering a period of 2.5 years; starting 6 months after the disclosure of the test results showing the woman to be a carrier of the gene causing Huntington's disease. ETHICAL CONSIDERATIONS: Even though the study was extremely sensitive, where potential harm constantly had to be balanced against the benefits, the couple had a strong wish to contribute to increased knowledge about people in their situation. The study was approved by the ethics committee. FINDINGS: The results show that the long-term consequences were devastating for the family. This 3-year period was characterized by anxiety, repeated suicide attempts, financial difficulties and eventually divorce. DISCUSSION: By offering a predictive test, the healthcare system has an ethical and moral responsibility. Once the test result is disclosed, the individual and the family cannot live without the knowledge it brings. Support is needed in a long-term perspective and should involve counselling concerning the families' everyday life involving important decision-making, reorientation towards a new outlook of the future and the meaning of life. CONCLUSION: As health professionals, our ethical and moral responsibility thus embraces not only the phase in direct connection to the actual genetic test but also a commitment to provide support to help the family deal with the long-term consequences of the test.