This article presents a set of moral arguments regarding the selective abortion of fetuses on the basis of prenatal screening for late onset genetic diseases only, and for Huntington's Disease* in particular. After discussion of human suffering, human perfection and the distinctive features of the lives of people confronting late onset genetic disease, the author concludes that selective abortion is difficult to justify ethically, although it must remain a matter of personal choice.

ABSTRACT The objective of the study was to identify future lawyers’ and physicians’ views on testing children for Huntington’s disease (HD) against parents’ wishes. After receiving general information about HD, patient autonomy and confidentiality, law students and advanced medical students were shown an interview with a mother suffering from HD who is opposed to informing and testing her two children (aged 10 and 16) for HD. Students then filled out questionnaires concerning their agreement with testing. No significant differences were (...) found between medical and law students or between students from different courses concerning the adolescent son. Three quarters of students thought that he should be told about his mother’s disease, and 91% thought the adolescent son should have the opportunity of genetic testing for HD for himself. However, significant differences were found concerning the 10‐year old son, with 44% of law students and 30% of medical students in favour of testing the child for HD. Students raised some important ethical issues in their elective comments. In conclusion, we found highly positive attitudes towards informing a 16‐year old of his mother’s HD and offering to test him. These attitudes were not in tune with guidelines. Students did not consider several practical and ethical issues of genetic testing of children and adolescents. Specific education should ensure that attitudes are based on sufficiently detailed knowledge about all aspects of genetic testing of children to discourage pressures on persons at risk of HD. (shrink)

What ethical justification can be found for informing a person that he or she will later develop a lethal disease for which no therapy is available? This question has been discussed during the past twenty years by specialists concerned with the prevention of Huntington's Disease, an incurable late-onset hereditary disorder. Many of them have played an active role in developing experimental testing programmes for at-risk persons. This paper is based on a corpus of 119 articles; it reviews (...) the development of their reflection and includes an outline of the ethical problems identified and the solutions adopted in pre-clinical protocols. Seen in a broader perspective, the experience of presymptomatic testing for Huntington's Disease has given medical geneticists the opportunity to clarify their ethical position in the as yet little explored field of predictive medicine. (shrink)

Activating the ERK pathway (extracellular signal‐regulated kinase pathway) has proven beneficial in several models of Huntington's disease (HD), and drugs that are protective in HD models have recently been found to activate ERK. Thus, the ERK cascade may be a potential target for therapeutic intervention in this currently untreatable disorder. HD is caused by an expanded polyglutamine repeat in the huntingtin (Htt) protein that actuates a diverse set of pathogenic mechanisms. In response to mutant Htt, ERK is activated (...) and directs a protective transcriptional response and inhibits caspase activation. Paradoxically, Htt also interferes with several signaling events of the ERK pathway. Mutant Htt compromises the ERK‐dependent transcriptional response to corticostriatal BDNF signaling. Mutant Htt also hinders glutamate uptake from the synaptic cleft by down‐regulating ERK‐dependent expression of glutamate transporters, leaving cells vulnerable to excitotoxicity. Some of this cellular complexity can be capitalized on to achieve selective activation of ERK, which can be protective. (shrink)

Ghosn, Mariam Huntington's disease (HD) is an inherited disorder. Sufferers usually develop symptoms in midlife between the ages of 30 and 50 years. HD causes neurodegeneration resulting in the progressive development of physical, cognitive and emotional symptoms. The impact on sufferers worsens over time with the final stage of the disease resulting in the need for professional assistance in a long-term care facility. More rarely HD develops in children and young adults, with less than 5% of HD (...) sufferers being affected by Juvenile HD. This article considers the ethical aspects of such testing. (shrink)

Ghosn, Mariam Predictive genetic testing Part 2 will examine the issues and ethical aspects that must be considered when adolescents below the age of majority make a request to undergo predictive genetic testing for Huntington's disease.

SummaryThe incidence of family breakdown and stress has been examined in an unselected group of 92 South Wales families, each containing a patient suffering from Huntington's chorea, and related to the onset and duration of the disease, age of the patient, and behavioural symptoms shown. The frequency of actual and attempted suicide is analysed and the effects of the disorder on the primary care agent for the patient discussed. Some of the effects on children and the needs of (...) the families for support and practical help are outlined. It is concluded that family support is an essential factor in any programme aimed at the long-term alleviation and prevention of Huntington's chorea. (shrink)

The right not to know is underappreciated in policy-making. Despite its articulation in medical law and ethics, policy-makers too easily let other concerns override the right not to know. This observation is triggered by a recent decision of the Dutch government on embryo selection for Huntington’s disease. This is a monogenetic debilitating disease without cure, leading to death in early middle age, and thus is a likely candidate for preimplantation genetic diagnosis. People possibly affected with the Huntington gene (...) do not always want to know their genetic status themselves, which is very burdensome knowledge. For prospective parents, this creates a difficulty in having unaffected children through embryo selection without knowing their own genetic status. A solution is provided by the exclusion test: it allows embryo selection while honouring the parents’ right not to know. The Dutch government however disallowed the exclusion test and chose to allow PGD on Huntington only for parents who test themselves first. To avoid “unnecessary” in-vitro fertilisation procedures for unaffected parents, prospective parents are “forced to know” before they can conceive through embryo selection. This article analyses the scope of the right not to know in the context of embryo selection against Huntington’s disease. It concludes that the right not to know implies that PGD against Huntington should be allowed by means of the exclusion test. (shrink)

This paper recognizes the complexity of the debate on informed consent and discusses the importance of the ongoing process of consent for people affected by Huntington's disease (HD). Although written information may not be the most appropriate form of obtaining informed consent in qualitative research, it remains an important part of the ethical approval process for health research in the UK. This paper draws on a study in which the information sheet and consent form were specifically designed to (...) help obtain consent from people who may be impaired by the cognitive and physical effects of HD. The forms were developed by drawing on expert opinion and relevant literature and fall in line with recommendations from the Mental Capacity Act 2005 to encourage people to make their own decisions. The paper describes the feasibility of a method for obtaining consent as an ongoing process with patients affected by HD using information sheets and consent forms specifically designed for people with potential cognitive and/or physical impairments. In conclusion, this paper adds a pragmatic approach to the debate on informed consent by describing the development of a written information sheet and consent form being used in a current social research study. Particular emphasis is placed on the importance of written information being adapted according to the needs of potential participants. (shrink)

A 62-year-old female with Huntington’s disease presented after a suicide attempt. Her advance directive stated that she did not want intubation or resuscitation, which her family acknowledged and supported. Despite these directives, she was resuscitated in the emergency department and continued to state that she would attempt suicide again. Her suicidality in the face of a chronic and advancing illness, and her prolonged consistency in her desire to take her own life, left careproviders wondering how to provide ethical, respectful (...) care to this patient. Tension between the ethical principles of autonomy and beneficence is central in this case. The patient’s narrative demonstrated that her suicide was an autonomous decision, free from coercion or disordered thinking from mental illness. Beneficence then would seem to necessitate care aligned with the patient’s desire to end her life, which created ethical uneasiness for her family and careproviders. The case highlights several end-of-life ethical considerations that have received much recent attention. With ongoing discussions about the legalization of aid in dying across the country, caregivers are challenged to understand what beneficence means in people with terminal illnesses who want a say in their death. This case also highlights the profound moral distress of families and careproviders that arises in such ethically challenging scenarios. (shrink)

Presymptomatic testing for Huntington's disease has given rise to several ethical problems relating to such issues as confidentiality, the privacy of the individual, the testing of minors and informed consent in connection with blood sample donation. A multidisciplinary conference of staff from genetic centres involved with presymptomatic testing was organised in Cardiff to discuss these and other problems. Recommendations on good practice are described under four headings: pre- and post-test counselling; confidentiality in relation to test results; collection and (...) storage of DNA, and criteria for testing. (shrink)

Family carers of individual’s living with Huntington’s Disease (HD) manage a distinct and unique series of difficulties arising from the complex nature of HD. This paper presents the validation of the definitive measure of quality of life for this group. The Huntington’s Disease Quality of Life Battery for carers (HDQoL-C) was expanded and then administered to an international sample of 1716 partners and family carers from 13 countries. In terms of the psychometric properties of the tool, exploratory analysis (...) of half of the sample, demonstrated good internal consistency and reliability. Some items on the full version did not meet psychometric thresholds and a short version (HDQoL-Cs) was developed based on more stringent criteria. Confirmatory Factor Analysis of the model structure showed a good fit for all Factors and, indicated that the HDQoL-C and HDQoL-Cs are psychometrically robust measures of quality of life. We found that carers who lived with and looked after their spouse/partner had reduced sense of coping, hope for the future and overall quality of life. Carers with children who were at risk, carried the gene or were symptomatic also had poorer quality of life outcomes. Findings indicated the HDQoL-C and HDQoL-Cs are valid in multiple languages and across varied cultures as measures of self-reported quality of life in family carers of individual’s living with HD. These psychometrically validated tools can aid and guide the implementation of therapeutic interventions to improve life quality in this population. (shrink)

Several studies have reported impairment in the recognition of facial expressions of disgust in patients with Huntington's disease (HD) and preclinical carriers of the HD gene. The aim of this study was to establish whether impairment for disgust in HD patients extended to include the ability to express the emotion on their own faces. Eleven patients with HD, and 11 age and education matched healthy controls participated in three tasks concerned with the expression of emotions. One task assessed (...) the spontaneous production of disgust-like facial expressions during the smelling of offensive odorants. A second assessed the production of posed facial expressions during deliberate attempts to communicate emotion. The third task evaluated HD patients’ ability to imitate the specific facial configurations associated with each emotion. Foul odours induced fewer disgust-like facial reactions in HD patients than in controls, and patients’ posed facial expressions of disgust were less accurate than the posed disgust expressions of controls. The effect was selective to disgust; patients had no difficulty posing expressions of other emotions. These impairments were not explained by compromised muscle control: HD patients had no difficulty imitating the facial movements required to display disgust. Viewed together with evidence of difficulty in other aspects of disgust in HD, the findings suggest that a common substrate might participate in both the processing and the expression of this emotion. (shrink)

Euthanasia and physician-assisted suicide (PAS) by request and/or based on an advance directive are legal in The Netherlands under strict conditions, thus providing options for patients with Huntington's disease (HD) and other neurodegenerative diseases to stay in control and choose their end of life. HD is an inherited progressive disease characterised by chorea and hypokinesia, psychiatric symptoms and dementia. From a qualitative study based on interviews with 15 physicians experienced in treating HD, several ethical issues emerged. Consideration (...) of these aspects leads to a discussion about the professional role of a physician in relation to the personal autonomy of a patient. Such a discussion can raise awareness that talking about end-of-life wishes with an HD patient is part of the legal, professional and moral responsibility of the physician, and that a letter of intent on behalf of the physician can improve active participation in the process. Discussion of these issues can help to advance the debate on euthanasia and PAS in HD and other neurodegenerative diseases. (shrink)

The Benefits and Potential Harms of Genetic Testing for Huntington's Disease: A Case Study Content Type Journal Article Pages 14-19 Authors Kathryn Edge, BSC, Rheumatic Diseases Centre, CSB, Hope Hospital, The University of Manchester, Stott Lane, Salford M6 8HD, England Journal Human Reproduction & Genetic Ethics Online ISSN 2043-0469 Print ISSN 1028-7825 Journal Volume Volume 14 Journal Issue Volume 14, Number 2 / 2008.

The aim of this study was to describe the experiences of undergoing a presymptomatic genetic test for the hereditary and fatal Huntington’s disease, using a case study approach. The study was based on 18 interviews with a young woman and her husband from the decision to undergo the test, to receiving the results and trying to adapt to them, which were analysed using a life history approach. The findings show that the process of undergoing a presymptomatic test involves several (...) closely connected ethical and medical questions, such as the reason for the test, the consequences of the test results and how health-care services can be developed to support people in this situation. (shrink)

The aim of this study was to describe the experiences of undergoing a presymptomatic genetic test for the hereditary and fatal Huntington’s disease, using a case study approach. The study was based on 18 interviews with a young woman and her husband from the decision to undergo the test, to receiving the results and trying to adapt to them, which were analysed using a life history approach. The findings show that the process of undergoing a presymptomatic test involves several (...) closely connected ethical and medical questions, such as the reason for the test, the consequences of the test results and how health-care services can be developed to support people in this situation. (shrink)

BackgroundHuntington’s disease has a poor prognosis. For HD patients in the Netherlands, one way of dealing with their poor prognosis is by drawing up an advance euthanasia directive. Little is known about the perspectives of HD patients on their AED.AimTo gain insight into patients’ views on and attitudes towards their AED, and changes over time.MethodsA longitudinal qualitative interview study using 1 to 6 semi-structured interviews over a period of maximum three years. Nine HD patients who either had an AED (...) or were thinking about drawing it up participated in this study.ResultsWe identified two themes that characterize patients’ perspectives on their AEDs: general character of the AED; uncertainty around their AED. Ad The conditions that the participants described in their AED were generally not very specific for the person. Mostly they were general notions of unbearable suffering. Familiarity with HD in the family could play a role in drawing up an AED. Ad Participants generally were aware of the tentative character of their AED and could have doubts concerning their own willingness or the willingness of others in the future. Sometimes these doubts were so great, that it prevented them from drawing up an AED. However, patients did not alter their AED during the follow-up period or changed in their view or attitude on their AED.ConclusionHD patients that draw up an AED usually describe general conditions for euthanasia and recognize that these conditions may change as the disease progresses. An AED or the wish to draw one up may be a good conversation starter for conversations about goals and preferences for future care. (shrink)

This chapter considers ethical issues involved in genetic testing and screening for susceptibility to various forms of cancer.

When is commodification acceptable?Preimplantation genetic diagnosis is usually restricted to couples who are eligible for in vitro fertilisation —infertile couples or those with a history of genetic disease. The Human Fertilisation and Embryology Authority in England and the Infertility Treatment Authority in Australia have both given permission for PGD with tissue typing to detect human leucocyte antigen compatibility in order to save an existing sibling with a life threatening condition. The procedure has also been carried out in the United (...) States.1Heavy criticism followed the February 2002 ruling of England’s HFEA to allow a family to try for a child who is free of thalassaemia and a “perfect match” for a sick sibling.2 Then in August …. (shrink)

Research and clinical trial development for rare diseases pose unique bioethical challenges. Much of the literature on rare diseases focuses on patient advocacy and drug development to manage or cu...

Until approximately twenty years ago, advances in the study of human genetics had little influence on the practice of medicine. In the 1980s, this changed dramatically with the mapping of the altered genes that cause cystic fibrosis and Huntington disease. In just a few years, these discoveries led to DNA-based tests that enabled clinicians to determine whether prospective parents were carriers of CF or whether an individual carried the Huntington gene and, as a result, would almost certainly develop the (...) disease.Observers interested in the social and economic implications of genetic technology realized that such genetic tests could be used by insurance companies to predict which insurance applicants were likely to become ill or even die from these diseases. (shrink)