A theoretical psychological perspective on predictive testing for late onset hereditary diseases.

Because of the burden of serious late onset hereditary diseases, psychological counselling is commonly included in the predictive testing procedure. We discuss the components of psychological counselling in the context of neurodegenerative disorders such as Huntington's disease, some hereditary cancers and some hereditary heart diseases. Psychological counselling should be tailored to the specific characteristics of the disease: penetrance and expression of the mutation, variability of the age at onset and efficacy of prevention and treatment, if available. Finally theories that have already been used for the psychological framing of counselling in the context of predictive testing or to formulate research hypotheses (e.g. Transactional Model of Stress and Coping, Common Sense Model of Self-regulation) are discussed.

Predictive testing for hereditary breast and ovarian cancer: a psychological framework for pre-test counselling.

Since the identification of two breast-ovarian cancer susceptibility genes (BRCA1/2), predictive testing for hereditary breast/ovarian cancer (HBOC) has been available. Given the complexity and uncertainties of HBOC and the potential impact of predictive testing on psychological well-being, we offer the test applicants a combination of information-oriented and psychological counselling. In this paper, we describe the multidisciplinary approach for predictive testing for HBOC as a clinical service in Leuven, hereby focusing on psychological and decision counselling practice. Attention is paid to the theoretical framework used for pre-test psychological counselling in Leuven. We discuss three important interacting dimensions of psychological counselling: individual emotional support, decision counselling and support of the family communication process. Decision counselling consists of an evaluation of the cognitive and the emotional processing of the information given and strategies and resources for coping. This serves as a starting point to facilitate free informed decision making. Scenario development is used as a decision aid.

Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?).

Huntington's disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = -0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (-0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.

Adolescents' attitude towards carrier testing for cystic fibrosis and its relative stability over time.

Attitudes towards cystic fibrosis (CF) carrier testing, benefits of and barriers to having such a test were assessed within a randomly selected group of high school students in Flanders, after they had received sufficient basic information about the nature and the mode of inheritance of CF. Attitudes towards carrier testing for CF were not negative, but the majority preferred to wait to have a test. This result changed little after 6 months. A hypothetical testing offer from the Medical School Health Service elicited positive answers from nearly two thirds, suggesting that such an offer may function as a cue to action. Nevertheless, the appropriateness of such an offer may be questioned, considering the disadvantages of testing adolescents. Concern about a negative impact of the carrier status on self-image was reported by 10% of the students. These findings suggest that education about genetics is not only a prerequisite for allowing more informed decisions about CF carrier testing, but also for avoiding negative psychosocial effects of such a test.

Non-participation in predictive testing for Huntington's disease: individual decision-making, personality and avoidant behaviour in the family.

Subjective risk perception, perceived impact of Huntington's disease (HD), perceived benefits and barriers of predictive testing and personality characteristics of persons withdrawing from the predictive test programme for HD and of siblings of test applicants were studied in a mailed survey. The belief that important decisions do not need to depend on a test result and the anticipated inability to cope with a bad result played an important role in the decision not to be tested. Nevertheless half of the group who ever considered testing, still planned to undergo a test in the future. A comparison of tested and untested persons revealed that the first group is more likely to overestimate the risk than the second group, but that both groups did not significantly differ from each other regarding anxiety, ego strength and coping strategies. An intrafamilial analysis of tested and untested siblings confirmed these findings. The problems during data collection and the reasons for the dropout are an illustration of the avoidant behaviour regarding HD and the predictive test in many individuals and families.

Personality profile in adult female fragile X carriers: assessed with the Minnesota Multiphasic Personality Profile (MMPI).

To assess if the higher incidence of psychiatric morbidity in fragile X carriers is related to a particular pathological personality profile, we obtained a Minnesota Multiphasic Personality Profile from 11 normally intelligent (female) fragile X carriers. The sample mean for the clinical and validity scales all fell within the normal range. Although no pathological profile was found, some unexpected results emerged: low scores for the scales "schizophrenia" and "social introversion" and a so-called faking-good profile on the validity scales. This combination suggests that the subjects might not be aware of some personality characteristics in these areas. Implications for further research are discussed.

Triple Test Screening for Down Syndrome: Looking Back on a False-Positive Result and Having or Not Having a Triple Test in Subsequent Pregnancies.

Objectives: It was the main aim of the present retrospective study carried out in Flanders to evaluate how women with a false-positive triple test result look back on their experience and decision making and how many of them make use of the triple test in subsequent pregnancies. Methods: All 508 women tested in the Centre for Human Genetics in Leuven in 1995 who had a positive triple test result followed by a normal amniocentesis outcome were invited to participate in a mailed questionnaire study with open and multiple choice questions in 1998. The response rate was 68%. Results: The answers to the multiple choice question assessing how they look back on their initial expectations regarding the exact meaning of the triple test revealed that less than one half reported that it concerned the identification of 'a higher risk of carrying a child with Down syndrome (DS)'. Reporting correct initial expectations was significantly associated with a higher education level. The same holds for indecisiveness regarding pregnancy termination should the amniocentesis have detected a fetus with DS. As expected, a large majority of the women reported a high level of distress or worry after the communication of the positive triple test result. Overall the findings show that retrospectively most women had the feeling that the decision to have amniocentesis was their own decision rather than a professional's. Of the subgroup with one or more subsequent pregnancies 70% had another triple test. Conclusions: The overall results of this study clearly reveal a need for a systematic approach aimed at better informing and counselling pregnant women about the implications and limitations of the triple test. Notwithstanding the reported high level of distress caused by a positive triple test result, a large majority of the women with subsequent pregnancies had another triple test; they represent a clearly higher percentage than in another recent study. Copyright 2001 S. Karger AG, Basel

The psychological complexity of predictive testing for late onset neurogenetic diseases and hereditary cancers: implications for multidisciplinary counselling and for genetic education.

Increasing knowledge about the human genome has resulted in the availability of a steadily increasing number of predictive DNA-tests for two major categories of diseases: neurogenetic diseases and hereditary cancers. The psychological complexity of predictive testing for these late onset diseases requires careful consideration. It is the main aim of the present paper to describe this psychological complexity, which necessitates an adequate and systematic multidisciplinary approach, including psychological counselling, as well as ongoing education of professionals and of the general public. Predictive testing for neurogenetic diseases--in an adequate counselling context--so far elicits optimism regarding the short- and mid-term impact of the predictive test result. The psychosocial impact has been most widely studied for Huntington's disease. Longitudinal studies are of the utmost importance in evaluating the long-term impact of predictive testing for neurogenetic diseases on the tested person and his/her family. Given the more recent experience with predictive DNA-testing for hereditary cancers, fewer published scientific data are available. Longitudinal research on the mid- and long-term psychological impact of the predictive test result is essential. Decision making regarding health surveillance or preventive surgery after being detected as a carrier of one of the relevant mutations should receive special attention. Tailoring the professional approach--inside and outside genetic centres--to the families' needs is a continuous challenge. Even if a continuous effort is made, several important questions remain unanswered, last but not least the question regarding the best strategy to guarantee that the availability of predictive genetic testing results in a reduction of suffering caused by genetic disease and in an improvement of the quality of life of families confronted with genetic disease.

Predictive testing for Huntington's disease: a challenge for persons at risk and for professionals.

About a decade ago the introduction of predictive testing for Huntington's disease (HD) was an important milestone in medical history. The aim of the present paper concerning predictive DNA-testing for HD is fourfold. First of all it describes the professional challenge of elaborating an adequate test protocol and of permanently using a multidisciplinary approach to deal with predictive test requests. Secondly the paper is aimed at unraveling the factors that play a part in uptake and decision making regarding predictive testing. Hereby the Health Belief Model is used as a framework for understanding differences between tested and untested persons. Thirdly the impact of the test result on psychological well-being is reviewed. Finally this paper assesses the utilisation of prenatal diagnosis after predictive testing for HD and reflects on the psychological and ethical implications of different types of prenatal tests, including preimplantation genetic diagnosis.

Predictive testing for Huntington's disease: risk perception, reasons for testing and psychological profile of test applicants.

In the Center for Human Genetics in Leuven, predictive DNA-testing for Huntington's disease is available as a clinical service since November 1987, initially by DNA-linkage and since mid 1993 by direct mutation analysis. The multidisciplinary approach as well as the detailed test protocol are described. The present paper gives a sociodemographic description of the test applicants, their subjective evaluation of the risk and their motives for requesting the predictive test. Major attention is paid to the personality profile of the applicants who proceeded with testing. Psychometric testing revealed that this group of test applicants did not differ significantly from the general population for most characteristics and even had a number of more positive characteristics e.g. a higher ego-strength. The latter may reflect a self-selection of a more resourceful and emotionally healthier subgroup of at-risk persons. Nevertheless psychological evaluation also has identified a number of applicants with extremely high anxiety levels and other problems, who needed extra pretest and posttest counseling. The relatively high number of withdrawals from the test programme is another indication of the importance of adequate pretest counseling.

Diagnostic potential of open lung biopsy in mechanically ventilated patients with diffuse pulmonary infiltrates of unclear aetiology.

Acute respiratory failure with bilateral pulmonary infiltrates is a clinical problem with a wide differential diagnosis. We evaluated whether open lung biopsy offered a diagnosis and therapeutic guidance in cases of unclear diagnosis after non-invasive tests. For this purpose, we reviewed 60 cases of open lung biopsy performed between 2002 and 2009 in patients with acute respiratory failure and bilateral infiltrates at the intensive care unit of Ghent University Hospital. Pathological diagnosis was classified as specific or non-specific and its contribution to therapy and decision-making was evaluated by a panel of three intensive care unit physicians. We found that a specific pathological diagnosis was present in 39 open lung biopsy patients (65%; 95% confidence interval 52 to 76%): idiopathic interstitial pneumonia in 24 patients, malignancy in four patients, pulmonary infectious disease in nine patients, and a combination of specific diagnoses in two patients. Open lung biopsy contributed to patient management in 53 cases (88%) as it led to the initiation, modification or discontinuation of therapeutic drugs in 36, and contributed to the decision to continue or withdraw ventilator support in 17. Complications of open lung biopsy were noted in 14 patients (23%). We conclude that open lung biopsy was a useful diagnostic intervention in of a selected group of patients with acute respiratory failure and bilateral infiltrates of unclear clinical diagnosis, as it offered a specific diagnosis in 65%.

Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.

This prospective study evaluates emotional functioning and illness representations in 68 unaffected women (34 carriers/34 noncarriers) 1 year after predictive testing for BRCA1/2 mutations when offered within a multidisciplinary approach. Carriers had higher subjective risk perception of breast cancer than noncarriers. Carriers who did not have prophylactic oophorectomy had the highest risk perception of ovarian cancer. No differences were found between carriers and noncarriers regarding perceived seriousness and perceived control of breast and ovarian cancer. Mean levels of distress were within normal ranges. Only few women showed an overall pattern of clinically elevated distress. Cancer-specific distress and state-anxiety significantly decreased in noncarriers from pre- to posttest while general distress remained about the same. There were no significant changes in distress in the group of carriers except for ovarian cancer distress which significantly decreased from pre- to posttest. Our study did not reveal adverse effects of predictive testing when offered in the context of a multidisciplinary approach.

Perception of predictive testing for Huntington's disease by young women: preferring uncertainty to certainty?

Opinions on the implications of predictive testing for Huntington's disease were evaluated in a group of 169 women (aged 21-35 years) with interest in psychosocial issues, but with no special pre-existing knowledge or training in genetics. Predictive testing for Huntington's disease (HD) is considered to be a test case for predictive testing for other late onset diseases, monogenic as well as multifactorial disorders. In the hypothetical situation of having a 50% risk for developing HD, about half of the group expressed interest in a predictive test. As to the question of giving results of predictive tests to third parties, the group would be very reluctant to inform the employer or the insurer, but not their own family. Prenatal testing for late onset diseases was considered acceptable by half of the women; only one quarter of the total group would terminate a pregnancy of a child that might develop a late onset disease. The assessment of attitudes towards predictive testing was carried out within the context of a global evaluation of perceived advantages and disadvantages of genetic counselling. The attitudes towards predictive testing were systematically associated with perceiving 'having more certainty about the future' as an advantage of genetic counselling and with rejecting 'knowing everything in advance' as a disadvantage.

Uptake and impact of carrier testing for cystic fibrosis. A review and a theoretical framework about the role of knowledge, health beliefs and coping.

The first aim of the paper is to review research into the uptake of carrier testing for cystic fibrosis and into the impact of carrier testing on self-esteem, risk perception and reproductive decisions. The second aim is to connect the most important findings to psychological theories and concepts. Thirdly, we infer practical suggestions for genetic counselling. The uptake of genetic testing for CF could be explained by at least three (complementary) interrelated psychological concepts: the (lack of) genetic information, the individual's health beliefs and the concept of coping with a health threat. Cognitive and/or emotional coping mechanisms played also an important role in preserving self-esteem after a positive carrier test and in the subjective evaluation of the residual risk after a negative test result. Suggestions are given regarding genetic counselling in general and regarding free informed decision making.

Cystic fibrosis: community knowledge and attitudes towards carrier screening and prenatal diagnosis.

The rate of technical advance in genetics contrasts sharply with the slow diffusion of information on this subject to the general population. In this paper, we investigate the initial knowledge about cystic fibrosis of a group of adults with increased interest in psychosocial issues, but with no special pre-existing knowledge or training in genetics. Attitudes towards carrier screening and prenatal diagnosis for CF were also evaluated, after brief written information had been given on this disease. We found that the studied group had only a poor knowledge of the nature of CF and an even more limited awareness of its inheritance. This knowledge was mainly associated with educational level. Most respondents had no objections to population-wide carrier screening for CF, at least if the test was proposed and not systematically imposed by the government. It is striking that a smaller proportion were interested in knowing their own carrier status. The majority of the group were in favour of prenatal diagnosis for CF. Factors associated with knowledge and attitudes are described. In the discussion, special attention is paid to the psychosocial complexity of mass screening.

Cognitive representations of breast cancer, emotional distress and preventive health behaviour: a theoretical perspective.

Individuals at high risk for developing breast and/or ovarian cancer are faced with difficult decisions regarding genetic testing, cancer prevention and/or intensive surveillance. Large interindividual differences exist in the uptake of these health-related services. This paper is aimed at understanding and predicting how people emotionally and behaviourally react to information concerning genetic predisposition to breast/ovarian cancer. For this purpose, the self-regulation model of illness representations is elaborated. This model suggests that health-related behaviour is influenced by a person's cognitive and emotional representation of the health threat. These representations generate coping behaviour aimed at resolving the objective health problems (problem-focussed coping) and at reducing the emotional distress induced by the health threat (emotion-focussed coping). Based on theoretical considerations and empirical studies, four interrelated attributes of the cognitive illness representation of hereditary breast/ovarian cancer are described: causal beliefs concerning the disease, perceived severity, perceived susceptibility to the disease and perceived controllability. The paper also addresses the complex interactions between these cognitive attributes, emotional distress and preventive health behaviour.

Longitudinal study evaluating neuropsychological changes in so-called asymptomatic carriers of the Huntington's disease mutation after 1 year.

OBJECTIVES: To determine (1) whether the battery of neuropsychological tests was sufficiently sensitive to find differences between symptomatic patients with Huntington's disease (HD) and clinically asymptomatic individuals carrying the HD gene (AGC) and individuals without the HD gene (NGC) and (2) whether increasing cognitive impairment is found in AGC as compared with NGC. METHODS: A case-control, single-blind study comparing subjects with clinically manifest HD (n=21), AGC (n=12) or NGC (n=11) and a 1-year follow-up of AGC and NGC. Genotype for the HD gene was determined by molecular testing. A large battery of neuropsychological tests measuring several cognitive domains was performed. RESULTS: On most neuropsychological tasks, HD patients perform significantly worse than AGC and NGC. At baseline and follow-up examination, compared with NGC, AGC had lower scores on the symbol digit modalities test. Scores on a block span task declined more rapidly among AGC than among NGC. CONCLUSION: Cognitive impairments in HD patients are found when compared with clinically asymptomatic individuals carrying the HD mutation. Furthermore, our results suggest that subtle cognitive deficits are present in asymptomatic persons who have inherited the HD gene.

Predictive testing for Huntington's disease: relationship with partners after testing.

This study focuses on the partner relationship of tested persons, 5 years after their predictive test result for Huntington's disease (HD). We describe changes in marital status, quality of the relationship, and perceived changes in the relationship. Twenty-six carriers, 14 of their partners, 33 non-carriers, and 17 of their partners participated in the study. Qualitative and quantitative methods were used. For the majority of tested persons (about 70%), the marital status was unchanged 5 years post test. Overall, carriers rated the quality of the relationship higher than their partners did and they perceived more positive changes. Qualitative data show that a test result leading to changed roles may induce significant marital distress. Another consequence of the test may be the changes in dynamics in asymptomatic carrier couples. A pre-test discussion of the possible impact of the test result on the relationship should result in a better preparation for and more understanding of the reactions after testing. Counselling after testing should stimulate an open communication between partners with consideration of needs and anxieties of both partners.