Attitudes toward presymptomatic testing in Huntington disease

One hundred thirty-one individuals at 50% risk of inheriting Huntington disease (HD) responded to a survey to study their attitudes toward taking a genetic test based on the identification of a genetically linked DNA polymorphism. Ninety-six percent of the respondents believe that presymptomatic testing should be available, and 66% say they will use it themselves. Fewer married individuals, in comparison to those single, separated, and divorced, intend to take the test. Many respondents (40%) said their primary reason for wanting to be tested is to end the uncertainty in their lives. Results suggest that there will be self-selection in test use, with many individuals who believe they will be depressed or possibly suicidal with a positive test result deciding not to be tested or unsure about testing. However, 15% of those who want to be tested acknowledge that they may be at risk for suicide if they are probable gene carriers. Only 12% of all respondents say they will be likely to use prenatal testing, suggesting that initial demand may be low in New England. Implementation of presymptomatic testing challenges health care providers to develop strategies to care for otherwise healthy persons who will be given a diagnosis years before the onset of illness.     

Long-term outcome of presymptomatic testing in Huntington disease

Our study on long-term outcome of presymptomatic testing for Huntington disease had two aims: the comparison of the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and the identification of psychological determinants to improve care/support of testees. We performed a cross-sectional study of 351 persons who underwent presymptomatic testing. Those who had motor signs were excluded from the comparison of asymptomatic carrier and non-carriers. A structured interview including five self-report scales and the MINI (Mini International Neuropsychiatric Inventory) was proposed to detect a psychopathology or problem with social adjustment.We interviewed 119 testees (53%), 62 non-carriers and 57 carriers after a mean delay of 3.7 years (range: 0.32 to 8.9) after their result. Depression was frequent in asymptomatic carriers (58%). Interestingly, the self reported impact of the test showed that 27% of non-carriers did not cope well with a favourable result, and a significant percentage of non-carriers (24%) were depressed during follow-up. Multivariate analysis showed that only a previous episode of depression was predictive of depression after genetic testing in both carriers and non-carriers of the HD mutation (P<0.0001).Psychological support is necessary for all testees regardless of the result of their presymptomatic test, because psychiatric care is often needed by both carriers and non-carriers.     

Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families

One hundred and thirty-six individuals with a family history of X-linked adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN) were given a questionnaire surveying their sociodemographic characteristics, knowledge of X-linked inheritance, and attitudes toward prenatal, presymptomatic, and carrier testing. Of the respondents, 68% indicated that they would use prenatal testing. Of these, 57.1% would terminate a pregnancy of a male fetus hemizygous for the ALD gene and 13.5% would reportedly choose to terminate a heterozygote female fetus. Presymptomatic testing would be used by 88.7% of respondents to test at-risk sons and carrier testing would reportedly be used by 95.4% of respondents to test their at-risk daughters. Respondents correctly answered an average of 61% of the questions testing understanding of X-linked inheritance. This indicates a strong interest in prenatal, presymptomatic, and carrier testing and a need for genetic counselors to provide information about these available tests and X-linked inheritance.     

Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families.

One hundred and thirty-six individuals with a family history of X-linked adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN) were given a questionnaire surveying their sociodemographic characteristics, knowledge of X-linked inheritance, and attitudes toward prenatal, presymptomatic, and carrier testing. Of the respondents, 68% indicated that they would use prenatal testing. Of these, 57.1% would terminate a pregnancy of a male fetus hemizygous for the ALD gene and 13.5% would reportedly choose to terminate a heterozygote female fetus. Presymptomatic testing would be used by 88.7% of respondents to test at-risk sons and carrier testing would reportedly be used by 95.4% of respondents to test their at-risk daughters. Respondents correctly answered an average of 61% of the questions testing understanding of X-linked inheritance. This indicates a strong interest in prenatal, presymptomatic, and carrier testing and a need for genetic counselors to provide information about these available tests and X-linked inheritance.     

Attitudes of persons at risk for Huntington disease toward predictive testing

Attitudes of 69 persons at risk for Huntington disease (HD) were obtained by means of semistructured interviews and questionnaires. About 79% of the individuals said that they would use a presymptomatic predictive test if it were available. All believed that the test should be made available even though there was no cure for HD. Nearly 2/3 of subjects would use the test for prenatal diagnosis, and of these 71% would terminate a pregnancy if the fetus was found to carry the HD gene. Most subjects believed that pretest counseling should be mandatory and many said that testing should be withheld from persons who were psychologically unstable or were threatening self-harm. The data suggest that about 2-6% of persons at risk for HD may have severe psychiatric or suicidal responses to a positive outcome of predictive testing. This underscores the need for adequate pretest counseling and the availability of professional and community resources to deal with the impact of predictive testing on individuals and their relatives.     

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.     

"You have shown me my end": attitudes toward presymptomatic testing for familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a lethal degenerative motor neuron disease. Approximately, 5-10% of cases of ALS are familial (FALS), inherited primarily as an autosomal dominant trait. Recently, mutations in Cu/Zn superoxide dismutase (SOD1) have been identified; 15-20% of familial cases carry this mutation, providing a marker for diagnosis, carrier testing, and prenatal detection. We assessed understanding of genetics of FALS in relatives of patients cared for at the Forbes Norris MDA/ALS Research Center in San Francisco. A total of 25 participants completed a questionnaire and semistructured interview. Of these, 60% would have gene testing for themselves; 36% believed testing of children or adolescents was a good idea. Overall knowledge of genetics of FALS was limited. Also, 24% of respondents understood the inheritance pattern of FALS; 64% were aware that not all individuals who had the gene would show symptoms in their lifetime. Families were confused about whether they would receive results from linkage studies. We recommend that: (1) physicians refer relatives of newly diagnosed individuals for genetic counseling and possibly psychological counseling; (2) investigators ensure that participants comprehend the purpose of gene identification is for research, not disclosure of individual results; (3) families be helped to understand how to keep abreast of medical and genetic advances; (4) following the model of Huntington disease (HD), consensus guidelines for FALS genetic counseling and testing be developed.     

Presymptomatic,prenatal, and exclusion testing for Huntington disease using seven closely linked DNA markers

Presymptomatic testing, prenatal diagnosis, or exclusion testing are now available for persons at risk for Huntington disease. These tests will reduce uncertainty, assist in life planning, and prevent the birth of potentially affected children. We present the results of presymptomatic tests for 37 applicants including two prenatal and one exclusion test in 23 families. We initially used the markers G8, H5.52, F5.53, and pTV20 (D4S10), p8 (D4S62), and pRB1.6 (D4S81) and extended the informativity of the test at a later stage with the markers pKP1.65, C4H, S1.5 (D4S43), 674 (D4S95), 157.9 (D4S111), and YNZ32 (D4S125). Applicants with an unsuitable family structure were not admitted to the test. Of the 37 applicants, 33 were informative. In our hands the most efficient strategy is first to use the markers H5.52 (D4S10), pRB1.6 (D4S81), 674 (D4S95), pKP1.65 (D4S43), 157.9 (D4S111), YNZ32 (D4S125), and 252.3 (D4S115). The overall informativity in our data set was 84% and in the most recent test we achieved a 90–95% informativity. The other markers are used only when the first set is not informative.     

Long-term impact of Huntington disease linkage testing

We performed a long-term follow-up of Huntington disease (HD) predictive testing (an average of 6 years post-test) for 16 of 20 people who received informative linkage test results. Although no pre-test or baseline psychological differences were noted between those with an increased versus a decreased risk of HD, the long-term impact was dramatically different in these two groups. The low-risk group reported less uncertainty, anxiety or worry, fear, and worry about children's risk, whereas the high-risk group reported either the same or increased concern in these areas. Those at low risk also acknowledged an increased sense of control and self-esteem, whereas those at high risk reported decreases or no changes. One high-risk individual reported chronic depression that had occurred since the testing. Additionally, those at low risk reported greater reliance and faith in spiritual or religious beliefs than those at high risk. The emotional impact of HD genetic testing justifies the continued utilization of pre- and post-test counseling protocols. Pre-test counseling should include discussion of the known risks and benefits of predictive testing, with special emphasis on the participant's expectations for future change and improvement. Although the psychological impact appears mostly favorable for those with decreased risk, there is risk for a decline in psychological well-being over time for those with an increased risk for HD. Am J. Med. Genet. 70:365–370, 1997. © 1997 Wiley-Liss, Inc.     

Presymptomatic, prenatal, and exclusion testing for Huntington disease using seven closely linked DNA markers.

Presymptomatic, testing, prenatal diagnosis, or exclusion testing are now available for persons at risk for Huntington disease. These tests will reduce uncertainty, assist in life planning, and prevent the birth of potentially affected children. We present the results of presymptomatic tests for 37 applicants including two prenatal and one exclusion test in 23 families. We initially used the markers G8, H5.52, F5.53, and pTV20 (D4S10), p8 (D4S62), and pRB1.6 (D4S81) and extended the informativity of the test at a later stage with the markers pKP1.65, C4H, S1.5 (D4S43), 674 (D4S95), 157.9 (D4S111), and YNZ32 (D4S125). Applicants with an unsuitable family structure were not admitted to the test. Of the 37 applicants, 33 were informative. In our hands the most efficient strategy is first to use the markers H5.52 (D4S10), pRB1.6 (D4S81), 674 (D4S95), pKP1.65 (D4S43), 157.9 (D4S111), YNZ32 (D4S125), and 252.3 (D4S115). The overall informativity in our data set was 84% and in the most recent test we achieved a 90-95% informativity. The other markers are used only when the first set is not informative.     

Counseling needs and attitudes toward prenatal diagnosis and abortion in fragile-X families

The genetic counseling need of 32 women of normal intelligence at-risk for having children with the fragile-X syndrome (FXS) were determined by a questionnaire study which included assessment of their attitudes toward prenatal diagnosis and the option of pregnancy termination. Eighteen (56%) of the women had one or more children with the FXS and 14 (44%) had no affected children. Twenty-six (81%) of the subjects stated that they would choose to have prenatal diagnosis and 9 (28%) indicated they would terminate an affected pregnancy. There was no significant difference between women who had affected children and those who did not have affected children, nor between Catholics and non-Catholics regarding acceptance of prenatal diagnosis. Catholic women were less likely to consider pregnancy termination than non-Catholics, but the majority of subjects (56%) were unsure what they would do if a fetus they were carrying was found to be affected. Issues the subjects considered most important for discussion with a genetic counselor included: 1) availability of treatment, 2) risk for having an affected grand child, 3) expectations for future functioning of affected children, and 4) availability of prenatal diagnosis.     

Autism spectrum disorders: a qualitative study of attitudes toward prenatal genetic testing and termination decisions of affected pregnancies

In the United States, prenatal genetic testing (PGT) for Autism Spectrum Disorders (ASD) is currently available via clinical genetic services. Such testing may inform parents about their unborn child's risk for ASD, prepare parents for the birth of an affected infant, and allow them to arrange for early interventions. Although PGT for autism has potential benefits, the associated ethical, legal, and social implications (ELSI) should be considered. This first qualitative study employed a hypothetical scenario to explore the attitudes toward PGT and termination decisions of 42 parents of children with ASD. Over half of the participants expressed willingness to undergo PGT for autism. Reasons included better preparation for birth, early and better treatment, termination of affected pregnancy, contribution to research, and curiosity. Of the 31 parents who were either willing or unsure about undergoing the PGT, approximately three‐fourths would continue their hypothetical affected pregnancies. Explanations included preparation for birth of the child, bonding or acceptance of existing ASD‐affected children, apprehensions about test limitations, and religious concerns. Parents who reported they would terminate the affected pregnancy in this hypothetical situation were primarily Asians. This study contributes to the growing understanding of the ELSI aspects of PGT in clinical practice.     

Predictive testing for Huntington disease in a developing country

Predictive testing for Huntington disease (HD), by means of direct mutation analysis, has been offered at the Division of Human Genetics, University of Cape Town, from 1995. The aim of this study was to compile a comprehensive profile of the participants who had undergone predictive testing in the Western Cape from 1995 to 2005. The sociodemographic data, uptake and outcome of tests were analyzed to inform changes to improve the current genetic counseling services. A retrospective cross-sectional design using a 'multi-method' approach of both qualitative and quantitative methods was used. Data were gathered from the participants' hospital files and genetic database. Psychosocial data were obtained by face-to-face interviews with the participants in their homes or venues of choice. A total of 36 predictive tests were performed. The uptake for predictive testing was approximately 4.5% of the estimated at-risk population. The cohort of 27 individuals comprised 16 females and 11 males. Their mean age was 35.3 years; 6 were mixed ancestry and 21 were White people (European ancestry); 11 tested gene positive, 15 gene negative and 1 was in the reduced penetrance range. The most important issue identified was that the uptake of individuals classified as mixed ancestry was substantially lower than that of the White people possibly due to limited access to the predictive testing program because of the low levels of income and education in the general population of families with HD. Strategies to address these aspects have been incorporated into the program and will be reassessed after 1 year.     

Predictive testing for Huntington disease: social characteristics and knowledge of applicants, attitudes to the test procedure and decisions made after testing

An investigation has been made of the social characteristics and knowledge and experience of Huntington disease (HD) for the first 80 individuals considering presymptomatic testing (applicants) at the medical genetics centres in Edinburgh and Glasgow and of attitudes to the test procedure and decisions made after testing for those who received a result. Sixty-one percent of applicants were female and 31% were over 40 years old. Almost all had a symptomatic parent but 38% did not know HD was in their family until they were over 25 years old and 48% had never received genetic counselling. Thirty-eight percent of applicants first heard of the test at the genetic clinic, 20% from a relative and 20% from the media, but none had received information from their GP. Thirty-one applicants did not have the test because they voluntarily withdrew (17 individuals), their family structure was unsuitable or no informative result was possible (11 individuals), or they were diagnosed clinically as being affected (3 individuals). Those who voluntarily withdrew did not differ significantly from the 49 who received a result in social characteristics or knowledge and experience of HD. Twenty-two individuals were found to be at increased risk (IR) (>50% of becoming affected) and 27 to be at decreased risk (DR) (< 50% of becoming affected). There was a median period of 9 months between entering the test procedure and receiving a result and the main criticism of the procedure was that it took too long to complete and several individuals experienced considerable anxiety while awaiting their result. One year after receiving their result, almost 40% of individuals had made major life decisions, mainly in the areas of personal relationships, career and financial matters and over a third of fecund individuals in both IR and DR groups had changed their decision about future childbearing. Eighty-five percent of the IR group and 53% of the DR group requested continued follow up after the 1-year follow-up visit. The majority wanted follow up by the genetic clinician, but we have found that in practice many individuals do not attend when offered clinic appointments after this time.