Journal of Genetic Counseling, Vol. 4, No. 2, 1995
CF Carrier Testing: Experience of Relatives Nancy P. Callanan, 1,4 Diane Bloom, 2 James R. Sorenson, 3 Brenda M. DeVellis, 3 and Brian Cheuvront 3
Consensus exists that genetic counseling and CF carrier testing should be offered to individuals with a positive family history of CE To learn more about their experience with genetic counseling and testing we conducted a series of structured telephone interviews and focus group discussions with individuals and couples who had undergone genetic counseling and carrier testing because of a family history of CE Traditional genetic counseling appears to have been effective for this population. Subjects generally report having a positive counseling experience and few difficulties upon learning their carrier status. Subjects were quite knowledgeable about CF and their carrier risk and were highly motivated to seek testing. They may not be representative of all individuals with a family history of CF however. For carriers, concerns about whether and when to have children tested, and concerns about insurance implications of carrier status may emerge sometime after the initial counseling. Strategies for addressing these concerns and for providing efficient and effective education and genetic counseling for people with a family history of CF need to be developed. KEY WORDS: CF; carrier testing.
1Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 2Bloom Research, Chapel Hill, North Carolina. 3Department of Health Behavior and Health Education, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4Correspondence should be directed to Nancy Callanan, Division of Genetics and Metabolism, CB # 7250 BSRC, UNC-Chapel Hill, Chapel Hill, North Carolina 27599. 83 1059-7700/95/0600-0083507.50/1© 1995NationalSocietyof Genetic Counselors, Inc.
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INTRODUCTION Cystic fibrosis (CF) is one of the most common genetic disorders in the North American Caucasian population with an incidence of 1 in 2500 live births. Approximately 1 in 25 Caucasians are CF gene carders (Boat, 1989). The currently available CF carrier testing by analysis of the common CF mutation (delta F508) and 6-12 additional mutations can identify 8595% of Caucasian CF gene carriers (U.S. Congress, Office of Technology Assessment, 1992a). Although general population carrier screening for CF is controversial, there is consensus that individuals with a family history of CF should be offered genetic counseling and CF carrier testing (Caskey et al., 1990; Weinblatt, 1993). We conducted a series of telephone interviews and focus groups to learn about the genetic counseling and CF carrier testing experiences of individuals with a family history of CE Focus groups and structured interviews are methods that can be used to gather qualitative data about subjects values, beliefs, attitudes, and preferences (Basch, 1987). We chose these methods because we were interested in learning about the subjects' personal experience with CF, the factors that influenced the decision to request genetic counseling and carrier testing, and their experience with the testing process. We were also interested in learning about any difficulties they had experienced as a result of CF carrier testing and how they coped with these difficulties. The information was used to help develop educational and counseling strategies for a CF Carrier Pilot Study targeted at individuals with a positive family history of CF.
BACKGROUND
CF carrier testing for relatives of an affected individual is highly accurate especially if both of the proband's CF mutations can be identified. If one or both mutations cannot be identified, or if the proband is unavailable for study, carrier testing for relatives can be accomplished by a combination of direct mutation analysis for the most common CF mutations and linkage analysis of closely linked gene markers (Beaudet, 1990). If an individual with a positive family history of CF is identified as a CF gene carrier, CF carrier testing is offered to the spouse or partner. Carrier testing by DNA analysis for the most common CF mutations can, depending on ethnicity, identify approximately 85-95% of Caucasian CF gene carriers. If the partner is also identified as a CF gene carder the couple faces a 1 in 4 risk with each pregnancy for having a child affected with CE Ge-
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netic counseling for these couples addresses the reproductive risk and options, including the availability of accurate prenatal diagnosis. If the partner has a negative CF carrier analysis (no CF mutation detected) the risk that the partner is a CF gene carrier is generally reduced to less than 1 in 150. The carder by "noncarrier" couple's risk of having a child with CF can be estimated to be less than 1 in 600 chances. The specific risk for any couple depends on the family history, ethnic background, and the type of testing performed. Because currently available CF carder testing is not 100% sensitive, some carder by "non-carrier" (+/-) couples are actually carder by carder (+/+) couples who remain undetected. Therefore genetic counseling about CF carrier testing for any individual or couple, regardless of family history requires a discussion of the limitations of the testing. Concerns about general population CF carder testing center on issues of test sensitivity, the need for effective pre-screening education, informed consent, and the availability of genetic counseling for individuals who test positive. The 1992 Office of Technology Assessment (OTA) survey of genetic counselors and nurses in genetics examined these and other issues including concerns about access to health insurance and the potential for discrimination and/or stigmatization of carriers identified by screening (U.S. Congress, Office of Technology Assessment, 1992b). These issues are important considerations not only for general population CF carder screening but also for carrier screening for individuals with a family history of CE
METHODS Recruitment
Thirteen couples who had a family history of CF and who had requested genetic counseling and/or carder testing at three University Medical Genetics Centers (University of North Carolina at Chapel Hill, Duke University Medical Center, Bowman Gray School of Medicine) within the past three years were contacted by their genetic counselor and asked to participate in small group discussion about their experience with CF counseling and testing. Three of the thirteen couples contacted had moved and could not be located. At least one member of each of the remanding ten couples agreed to participate. Three couples agreed to attend a 2-hour small discussion group. Each participant signed a consent form and was paid $25.00 for participation.
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Five couples and two individuals were unable to travel to attend the discussion group but agreed to be interviewed by telephone. These participants also signed a consent form and were paid $25.00 for participation. Description of Participants
1. Focus Groups Three couples participated in the focus groups. One member of each couple had a family history of CE In the first couple the woman had a brother with CF who was deceased. She was found by direct mutation analysis to be a CF gene carrier. Her husband had a negative CF mutation analysis. This couple was counseled that the risk for CF in their future children is about 1 in 600 chances. In the second couple, the man had a living brother with CE Carrier testing was done by a combination of direct mutation analysis and linkage testing and reduced this man's risk of being a CF gene carrier to less than 1%. His spouse was not tested. This couple's risk for having a child with CF is estimated to be about 1 in 10,000 chances. In the third couple, the man had a brother and a sister, both deceased, affected with CE He did not want to be tested. His spouse requested testing without his knowledge, though later told him of her test results. She had a negative CF mutation analysis. Based on the spouse's test results, this couple's risk of having a child with CF is estimated to be about 1 in 900 chances.
2. Telephone Interviews Five couples and two individuals were interviewed. One member of each of the five couples (three males and two females) had a living relative with CF (niece or nephew in four couples, sibling in one couple). Four of these individuals were found to be CF gene carders by direct mutation analysis. One individual, who was tested before the availability of direct mutation analysis, was found to be a CF gene carder by linkage analysis (99% accuracy). All five spouses were tested. Four spouses were tested by direct mutation analysis and three of these do not carry a common CF mutation (negative mutation analysis). The fourth spouse, however, was found to be a CF gene mutation carder. The fifth spouse who was tested prior to the availability of direct mutation analysis was tested by a linkage disequilibrium study which lowered the risk of being a carder to less than 1% (1 in 173 chances).
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All five couples had received genetic counseling prior to testing. The one couple who were both CF gene carriers returned for additional counseling regarding their reproductive risks and options. The remaining four couples did not return for additional counseling after learning their test results. One unmarried woman was also interviewed. She had both a sister and a niece with CE She did not have genetic counseling prior to testing. Direct mutation analysis revealed that she was a CF gene carrier, Her fiancee was tested and did not carry a common CF mutation. The couple received genetic counseling about their test results. At the time of the interview this woman was no longer engaged to the partner who had been tested. One married woman was interviewed. She had three relatives (one aunt and two uncles, all deceased) affected with CE She was identified as a CF gene carrier by direct mutation analysis. Her husband had a negative CF mutation analysis. He did not agree to be interviewed.
Topic Guide A topic guide for the focus groups and telephone interviews was developed in consultation with an experienced focus group facilitator. The subjects were first asked to describe their personal experience with and reactions to cystic fibrosis. Factors that influenced the decision to be tested, including risk perceptions, were explored. Subjects were asked to describe their questions and concerns prior to testing, their expectations for genetic counseling, their actual experience with the counseling and testing, their concerns while waiting for the test results, and their reactions, and the reactions of their spouses and relatives to the test results. Subjects were also asked to evaluate the counseling and testing process and to make recommendations for improving genetic counseling for individuals and couples with a family history of cystic fibrosis. Finally, all were asked how they would describe the process to others, and under what circumstances they would encourage others to seek genetic counseling.
Procedures 1. Focus Groups Two focus groups, one with three men and the other with three women were conducted simultaneously by experienced focus group facilitators following the topic guide. Each focus group included both carriers and non-
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carders. The groups lasted about 2 hours and were tape recorded with the subjects' consent.
2. Telephone Interviews The telephone interviews of 12 subjects were conducted by one of the focus group facilitators using the same topic guide with minor modifications to make it relevant for a one-on-one interview. These interviews lasted approximately 30 minutes and were recorded with the subjects' consent.
RESULTS The responses of subjects who participated in focus groups and those who were interviewed by telephone were similar and are summarized below. The intent of the focus groups and interviews was to probe in depth personal experiences with carrier testing and genetic counseling and reactions to them. Accordingly, our analysis of the transcripts followed established qualitative guidelines in identifying key themes and issues that emerged from the data rather than quantitative summaries of specific responses to direct probes or questions.
Knowledge of CF The first series of questions explored the subjects' knowledge of CF and their impressions of the disorder. Most reported significant knowledge of the disorder because of their exposure to the affected relative. Several had read about CF. When asked what words came to mind when they thought about CF, subjects' most frequent responses were "lung disease," "difficulty breathing," "digestive problems .... frequent illness," "suffering" and "early death." Spouses most frequently reported first learning about CF when they met their partner and his or her family. A few of the spouses had no direct contact with the affected relative because the person had died before they met the family. When asked about CF carders, subjects responded that they were "normal," or "healthy," but that they "could possibly have children with CE"
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Risk Perceptions
All subjects except one thought that the partner with an affected relative was likely to be a CF gene carder. "High chance," "50%," and "25%" were used to describe the risk. One man who had an affected niece thought that his chance of being a CF carrier was low. This man's wife, however, thought that his chance of being a carder was 50%. All subjects stated that the partner with no family history of CF had a low chance of being a CF carder. "Low," "1%," and "4%" were used to describe the partner's risk. Decision to Be Tested
When asked what factors contributed to the decision to be tested all subjects said they were tested because they were considering having a child. One couple was already pregnant at the time of testing. Most couples reported no disagreement between spouses regarding the decision to be tested. Two men, however, both with affected relatives, did not wish to be tested. One of these men was tested, to "satisfy his wife." The second man had not been tested. His wife was tested and had a negative mutation screen. He was "almost certain that he is a carrier" but thought that testing for him was not necessary since, based on his wife's testing he perceived their risk for having an affected child to be low. Prior to testing, subjects reported being concerned about having a child with CE They wondered if they were carders and if their partners were carriers. They also reported having questions about the availability of testing, how the testing was accomplished and the accuracy of the results. Furthermore, they had questions about what options would be available if both members of the couple were identified as CF carriers. Experience with Counseling and Testing
All subjects reported having a positive experience with genetic counseling. They reported that the counselor was knowledgeable and gave clear explanations. Subjects commented that pictures and diagrams used by the counselor were helpful. Subjects also reported that they had ample opportunity to ask questions and that their questions were answered; a few mentioned receiving a summary letter following counseling. Subjects expressed confidence in their genetic counselor; one man stated that the counselor made him feel "safer." The subjects saw the role of the genetic counselor as an educator, presenting information and options. They recognized the counselor's neu-
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trality in any decision making and thought that this was appropriate. The counselor helped identify important issues and questions that had not been raised. No subject reported being unduly anxious while waiting for the test result. Several mentioned that they were not anxious because the results came back within the expected time. Subjects reported that they learned their results either by telephone or letter and that this was appropriate. Given the opportunity to return for additional counseling after receiving the results, all but two couples declined. These couples attributed their declining further counseling to having the information they needed (carrier status) and not having additional questions. Notable exceptions were the couple who were both identified as gene carriers who returned for counseling to discuss reproductive options, and a woman who had not received counseling prior to testing. Reaction to Results
Subjects with a family history of CF reported that they were disappointed but not surprised to learn that they were CF gene carders. Their spouses' reactions were similar. With one exception, subjects did not report any long-term negative effects of learning that they or their spouse was a CF gene carrier. One female carrier described being "shocked and upset" upon learning her carrier status. She was uncertain about what to do next. She was concerned about the effect of being a CF carrier on her own health and wondered if she could develop CF in the future. This woman was engaged at the time of testing and felt that her carrier status may have contributed to the breakup of this relationship. She stated that her carrier status had "pushed her partner off" and "scared him." She mentioned that although it "eased his mind" to learn that they both needed to be carriers in order to have an affected child, they still broke up. It is of note that this woman did not receive genetic counseling prior to testing although she and her partner did have counseling after she learned the results of her testing. She told the interviewer that the counseling had helped resolve most of her questions and concerns. Understanding of Test Limitations
Subjects whose partners had a negative CF carder test reported being relieved to learn that the partner was most likely not a carrier. With few exceptions, the subjects understood the limitations of the carder testing. Expressions such as "low," "less than 1%," "virtually not a carrier," and
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"low, but no 100% guarantee" were used to describe the chance that a person with a negative test result could still be a CF gene carder. A few subjects responded even more specifically that the "test recognizes only 85% of CF genes" or that "the test could be wrong if the person carries a gene that could not be identified." Two subjects did not understand that a person with a negative mutation analysis still has a small chance of being a CF carder. In general, couples could accurately report their risk of having a child with CE A few stated that although they could not remember the exact number, they recall that the risk was "low" or "very low." Several volunteered that the risk seemed so low that they dismissed it altogether. Compared to the 1 in 4 risk for having a child affected with CF if they were both identified as carders this risk seemed inconsequential. Subjects also tended to compare the risk of having a child with CF to other risks, for example the general population risk for having a child with any birth defect. Reproductive Issues No subject reported any reproductive uncertainty as a result of the carrier testing. Although not asked about this directly, several subjects, mostly females, volunteered that they would not abort a pregnancy for CE One woman commented that she would have decided not to have children if both she and her husband were found to be CF carriers. Another woman commented that she worried during pregnancy that the test might have been wrong. One couple had both of their children tested for CF after delivery, even though they thought that their risk for having a child affected with CF was very low.
Other Concerns Several subjects expressed concern about their children's risk of being a CF gene carrier. A few mentioned their intention to tell their children about CF and to "have them tested." Subjects reported feeling disappointed and sad that their children would have to confront the issue of CF carder testing. Several had concerns and questions about the optimal timing for doing this. A few subjects raised concerns about the insurance implications of carrier testing, especially for their children, although no one had personally experienced any difficulties with this. No concerns were raised about employment discrimination.
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Subjects reported little difficulty sharing their test results with relatives. A few subjects, however, were reluctant to share the results with the parents of an affected relative. Generally, the women reported discussing carrier status more openly than the men. Recommendations for Others
Most subjects would recommend genetic counseling to others who had concerns about CF or other genetic conditions in the family, especially if they were planning on having children. When asked directly, subjects reported no disadvantages to CF carrier testing and described the value of the counseling and testing as providing knowledge and information and removing doubts.
DISCUSSION All of the participants in our study had requested genetic counseling and carrier testing themselves or specifically asked their doctor for a referral. They were also willing to participate in a focus group or be interviewed about their experience. Thus, they represent a group of individuals who were knowledgeable about CF and their carder risk and motivated to seek testing. Therefore, they may not be representative of all individuals with a family history of CE The reported positive experience with genetic counseling and CF carrier testing and the fact that few difficulties were encountered following testing may be due to factors such as a prior knowledge of CF, positive family adjustment to the diagnosis and family acceptance of genetic counseling in general. It is also possible that these subjects were more willing to talk about their experience because it had been positive. Several subjects raised concerns about their children's risk of being CF carriers. Questions were raised about whether and when to have the children tested. In this group of subjects there was no consensus about this issue. A few subjects also raised concerns about insurance implications of carrier testing, especially for their children. Most of our subjects requested testing because they were considering having a child. At the time of counseling the focus was generally on the potential risk of having a child affected with CE In our experience, couples rarely express any significant concern during counseling about the possibil-
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ity that their children will be CF gene carriers. Similarly, couples infrequently express concerns about the potential for insurance discrimination based on their or their children's carrier status. It is possible that these types of issues are more likely to emerge after counseling, especially for couples in which only one member is definitely identified as a CF gene carrier. There are limited data to guide genetic counselors on how to respond to these concerns (Billings, 1992). With the exception of the couple with both members who were identified as CF gene carriers and the unmarried woman who had not met with a genetic counselor prior to testing, the subjects elected not to return for additional counseling after learning their results. All couples who did not return for follow-up genetic counseling had counseling prior to testing; they reported having no additional questions or concerns upon learning their test results. It appears that genetic counseling prior to testing for individuals and couples with a positive family history of CF is a successful model for providing effective education and counseling. Subjects consistently reported a positive counseling experience and few difficulties upon learning their test results. The recent OTA survey of genetic counselors and nurses in genetics revealed that while many recognize the appropriateness of offering CF carrier screening to individuals with a positive family history, few counselors have routine contact with CF families. Although 55% of the survey participants responded that a CF Treatment Center exists at their institution, 86% reported that they do not provide genetic counseling through that facility. Furthermore, only 24% reported a large increase in the number of requests for CF carrier testing since the gene was isolated (U.S. Congress, Office of Technology Assessment, 1992b). At our institution genetic counseling is routinely provided for most parents of newly diagnosed CF children. The counseling includes a discussion of the carrier risks for relatives and the availability of accurate carrier testing. The family is encouraged to talk with their relatives about the risks and to have them contact the genetic counselor for more information. Despite these efforts we had only a small increase in requests for testing from relatives of affected individuals followed in our CF center. We recently completed a three year CF Carrier Screening Pilot Project in which we actively recruited subjects by requesting that CF patients (or their parents) provide us with information so that we could directly contact relatives to offer CF carrier testing. Approximately 54% of those contacted agreed to provide this information. Details of this study are reported elsewhere (Sorenson et al., 1994).
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In comparison to general population carder screening, testing relatives of affected individuals, or kinship-based testing, has several advantages. Individuals within a family have a higher prior risk of being o r d e r s . They also may have prior knowledge of and exposure to the disorder and therefore be more concerned and motivated to seek testing. It is important to develop efficient and effective models for providing CF carrier education and counseling for this population.
CONCLUSIONS This study employed focus group discussions and structured interviews to learn more about the experience of individuals who had requested CF carder testing and genetic counseling because of a positive family history of CE It was reassuring to learn that traditional genetic counseling appears to have been effective for this population. We were surprised to learn that for carriers, concerns about their children's carrier status and concerns about insurance implications of their carder status developed sometime after learning their results. Because most couples seek genetic counseling and carder testing for CF because of reproductive concerns, these issues might not routinely be addressed during the initial counseling. However, since many couples do not return for additional counseling after learning their test results it is important to address these issues at the time of the initial counseling. Genetic counselors strive to meet the needs of their clients by addressing their concerns and answering their questions. Focus groups and structured interviews are good techniques for identifying key issues to determine if current practices are meeting client needs.
ACKNOWLEDGMENTS The authors wish to thank A~yn McConkie-Rosell and Christina Ruiz for their help in recruiting subjects for this project. Supported in part by grant 5R01HG00643-02 from the National Center for Human Genome Research, Dr. Sorenson Principle Investigator.
REFERENCES Basch CE (1987) Focus group interview: An underutilized research technique for improving theory and practice in health education. Health Educ Quarterl 14(4):411-448.
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Beaudet AL (1990) Carrier screening for cystic fibrosis. Am J Hum Genet 47:603-605. Billings PR, Kohn MA, de Cuevas M, Beckwith J, Alper JS, and Natowiez MR (1992) Discrimination as a consequence of genetic testing. Am J Hum Genet 50:476-482. Boat "IT, Welsh MJ, Beaudet AL (1989) Cystic Fibrosis. In: Seriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic Basis of Inherited Disease. New York: McGraw Hill, pp 2649-2680. Caskey CT, Kaback MM, Beaudet, AL (1990) The American Society of Human Genetics Statement on cystic fibrosis screening. Am J Hum Genet 46:393. Sorenson JR, Cheuvront B, Brtming A, Talton S, DeVellis B, Koch G, Callanan N, Femald G (submitted) Proband and parent cooperation in an extended family cystic fibrosis carrier testing program. Am J Med Genet. U.S. Congress, Office of Technology Assessment (1992a) Cystic Fibrosis and DNA Tests: Implications of Carrier Screening. Washington, D.C.: US Government Printing Office. U.S. Congress, Office of Technology Assessment (1992b) Cystic Fibrosis and Genetic Screening: Policies, Practices and Attitudes of Genetic Counselors--Results of a Survey. Washington D.C.: US Government Printing Office. Weinblatt V (1993) Recommendations on Cystic Fibrosis Screening added to Society's Position Statements. Perspect Genet Counsel 15(2):9.
CF Carrier Testing: Experience of Relatives Nancy P. Callanan, 1,4 Diane Bloom, 2 James R. Sorenson, 3 Brenda M. DeVellis, 3 and Brian Cheuvront 3
Consensus exists that genetic counseling and CF carrier testing should be offered to individuals with a positive family history of CE To learn more about their experience with genetic counseling and testing we conducted a series of structured telephone interviews and focus group discussions with individuals and couples who had undergone genetic counseling and carrier testing because of a family history of CE Traditional genetic counseling appears to have been effective for this population. Subjects generally report having a positive counseling experience and few difficulties upon learning their carrier status. Subjects were quite knowledgeable about CF and their carrier risk and were highly motivated to seek testing. They may not be representative of all individuals with a family history of CF however. For carriers, concerns about whether and when to have children tested, and concerns about insurance implications of carrier status may emerge sometime after the initial counseling. Strategies for addressing these concerns and for providing efficient and effective education and genetic counseling for people with a family history of CF need to be developed. KEY WORDS: CF; carrier testing.
1Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 2Bloom Research, Chapel Hill, North Carolina. 3Department of Health Behavior and Health Education, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 4Correspondence should be directed to Nancy Callanan, Division of Genetics and Metabolism, CB # 7250 BSRC, UNC-Chapel Hill, Chapel Hill, North Carolina 27599. 83 1059-7700/95/0600-0083507.50/1© 1995NationalSocietyof Genetic Counselors, Inc.
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INTRODUCTION Cystic fibrosis (CF) is one of the most common genetic disorders in the North American Caucasian population with an incidence of 1 in 2500 live births. Approximately 1 in 25 Caucasians are CF gene carders (Boat, 1989). The currently available CF carrier testing by analysis of the common CF mutation (delta F508) and 6-12 additional mutations can identify 8595% of Caucasian CF gene carriers (U.S. Congress, Office of Technology Assessment, 1992a). Although general population carrier screening for CF is controversial, there is consensus that individuals with a family history of CF should be offered genetic counseling and CF carrier testing (Caskey et al., 1990; Weinblatt, 1993). We conducted a series of telephone interviews and focus groups to learn about the genetic counseling and CF carrier testing experiences of individuals with a family history of CE Focus groups and structured interviews are methods that can be used to gather qualitative data about subjects values, beliefs, attitudes, and preferences (Basch, 1987). We chose these methods because we were interested in learning about the subjects' personal experience with CF, the factors that influenced the decision to request genetic counseling and carrier testing, and their experience with the testing process. We were also interested in learning about any difficulties they had experienced as a result of CF carrier testing and how they coped with these difficulties. The information was used to help develop educational and counseling strategies for a CF Carrier Pilot Study targeted at individuals with a positive family history of CF.
BACKGROUND
CF carrier testing for relatives of an affected individual is highly accurate especially if both of the proband's CF mutations can be identified. If one or both mutations cannot be identified, or if the proband is unavailable for study, carrier testing for relatives can be accomplished by a combination of direct mutation analysis for the most common CF mutations and linkage analysis of closely linked gene markers (Beaudet, 1990). If an individual with a positive family history of CF is identified as a CF gene carrier, CF carrier testing is offered to the spouse or partner. Carrier testing by DNA analysis for the most common CF mutations can, depending on ethnicity, identify approximately 85-95% of Caucasian CF gene carriers. If the partner is also identified as a CF gene carder the couple faces a 1 in 4 risk with each pregnancy for having a child affected with CE Ge-
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netic counseling for these couples addresses the reproductive risk and options, including the availability of accurate prenatal diagnosis. If the partner has a negative CF carrier analysis (no CF mutation detected) the risk that the partner is a CF gene carrier is generally reduced to less than 1 in 150. The carder by "noncarrier" couple's risk of having a child with CF can be estimated to be less than 1 in 600 chances. The specific risk for any couple depends on the family history, ethnic background, and the type of testing performed. Because currently available CF carder testing is not 100% sensitive, some carder by "non-carrier" (+/-) couples are actually carder by carder (+/+) couples who remain undetected. Therefore genetic counseling about CF carrier testing for any individual or couple, regardless of family history requires a discussion of the limitations of the testing. Concerns about general population CF carder testing center on issues of test sensitivity, the need for effective pre-screening education, informed consent, and the availability of genetic counseling for individuals who test positive. The 1992 Office of Technology Assessment (OTA) survey of genetic counselors and nurses in genetics examined these and other issues including concerns about access to health insurance and the potential for discrimination and/or stigmatization of carriers identified by screening (U.S. Congress, Office of Technology Assessment, 1992b). These issues are important considerations not only for general population CF carder screening but also for carrier screening for individuals with a family history of CE
METHODS Recruitment
Thirteen couples who had a family history of CF and who had requested genetic counseling and/or carder testing at three University Medical Genetics Centers (University of North Carolina at Chapel Hill, Duke University Medical Center, Bowman Gray School of Medicine) within the past three years were contacted by their genetic counselor and asked to participate in small group discussion about their experience with CF counseling and testing. Three of the thirteen couples contacted had moved and could not be located. At least one member of each of the remanding ten couples agreed to participate. Three couples agreed to attend a 2-hour small discussion group. Each participant signed a consent form and was paid $25.00 for participation.
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Five couples and two individuals were unable to travel to attend the discussion group but agreed to be interviewed by telephone. These participants also signed a consent form and were paid $25.00 for participation. Description of Participants
1. Focus Groups Three couples participated in the focus groups. One member of each couple had a family history of CE In the first couple the woman had a brother with CF who was deceased. She was found by direct mutation analysis to be a CF gene carrier. Her husband had a negative CF mutation analysis. This couple was counseled that the risk for CF in their future children is about 1 in 600 chances. In the second couple, the man had a living brother with CE Carrier testing was done by a combination of direct mutation analysis and linkage testing and reduced this man's risk of being a CF gene carrier to less than 1%. His spouse was not tested. This couple's risk for having a child with CF is estimated to be about 1 in 10,000 chances. In the third couple, the man had a brother and a sister, both deceased, affected with CE He did not want to be tested. His spouse requested testing without his knowledge, though later told him of her test results. She had a negative CF mutation analysis. Based on the spouse's test results, this couple's risk of having a child with CF is estimated to be about 1 in 900 chances.
2. Telephone Interviews Five couples and two individuals were interviewed. One member of each of the five couples (three males and two females) had a living relative with CF (niece or nephew in four couples, sibling in one couple). Four of these individuals were found to be CF gene carders by direct mutation analysis. One individual, who was tested before the availability of direct mutation analysis, was found to be a CF gene carder by linkage analysis (99% accuracy). All five spouses were tested. Four spouses were tested by direct mutation analysis and three of these do not carry a common CF mutation (negative mutation analysis). The fourth spouse, however, was found to be a CF gene mutation carder. The fifth spouse who was tested prior to the availability of direct mutation analysis was tested by a linkage disequilibrium study which lowered the risk of being a carder to less than 1% (1 in 173 chances).
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All five couples had received genetic counseling prior to testing. The one couple who were both CF gene carriers returned for additional counseling regarding their reproductive risks and options. The remaining four couples did not return for additional counseling after learning their test results. One unmarried woman was also interviewed. She had both a sister and a niece with CE She did not have genetic counseling prior to testing. Direct mutation analysis revealed that she was a CF gene carrier, Her fiancee was tested and did not carry a common CF mutation. The couple received genetic counseling about their test results. At the time of the interview this woman was no longer engaged to the partner who had been tested. One married woman was interviewed. She had three relatives (one aunt and two uncles, all deceased) affected with CE She was identified as a CF gene carrier by direct mutation analysis. Her husband had a negative CF mutation analysis. He did not agree to be interviewed.
Topic Guide A topic guide for the focus groups and telephone interviews was developed in consultation with an experienced focus group facilitator. The subjects were first asked to describe their personal experience with and reactions to cystic fibrosis. Factors that influenced the decision to be tested, including risk perceptions, were explored. Subjects were asked to describe their questions and concerns prior to testing, their expectations for genetic counseling, their actual experience with the counseling and testing, their concerns while waiting for the test results, and their reactions, and the reactions of their spouses and relatives to the test results. Subjects were also asked to evaluate the counseling and testing process and to make recommendations for improving genetic counseling for individuals and couples with a family history of cystic fibrosis. Finally, all were asked how they would describe the process to others, and under what circumstances they would encourage others to seek genetic counseling.
Procedures 1. Focus Groups Two focus groups, one with three men and the other with three women were conducted simultaneously by experienced focus group facilitators following the topic guide. Each focus group included both carriers and non-
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carders. The groups lasted about 2 hours and were tape recorded with the subjects' consent.
2. Telephone Interviews The telephone interviews of 12 subjects were conducted by one of the focus group facilitators using the same topic guide with minor modifications to make it relevant for a one-on-one interview. These interviews lasted approximately 30 minutes and were recorded with the subjects' consent.
RESULTS The responses of subjects who participated in focus groups and those who were interviewed by telephone were similar and are summarized below. The intent of the focus groups and interviews was to probe in depth personal experiences with carrier testing and genetic counseling and reactions to them. Accordingly, our analysis of the transcripts followed established qualitative guidelines in identifying key themes and issues that emerged from the data rather than quantitative summaries of specific responses to direct probes or questions.
Knowledge of CF The first series of questions explored the subjects' knowledge of CF and their impressions of the disorder. Most reported significant knowledge of the disorder because of their exposure to the affected relative. Several had read about CF. When asked what words came to mind when they thought about CF, subjects' most frequent responses were "lung disease," "difficulty breathing," "digestive problems .... frequent illness," "suffering" and "early death." Spouses most frequently reported first learning about CF when they met their partner and his or her family. A few of the spouses had no direct contact with the affected relative because the person had died before they met the family. When asked about CF carders, subjects responded that they were "normal," or "healthy," but that they "could possibly have children with CE"
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Risk Perceptions
All subjects except one thought that the partner with an affected relative was likely to be a CF gene carder. "High chance," "50%," and "25%" were used to describe the risk. One man who had an affected niece thought that his chance of being a CF carrier was low. This man's wife, however, thought that his chance of being a carder was 50%. All subjects stated that the partner with no family history of CF had a low chance of being a CF carder. "Low," "1%," and "4%" were used to describe the partner's risk. Decision to Be Tested
When asked what factors contributed to the decision to be tested all subjects said they were tested because they were considering having a child. One couple was already pregnant at the time of testing. Most couples reported no disagreement between spouses regarding the decision to be tested. Two men, however, both with affected relatives, did not wish to be tested. One of these men was tested, to "satisfy his wife." The second man had not been tested. His wife was tested and had a negative mutation screen. He was "almost certain that he is a carrier" but thought that testing for him was not necessary since, based on his wife's testing he perceived their risk for having an affected child to be low. Prior to testing, subjects reported being concerned about having a child with CE They wondered if they were carders and if their partners were carriers. They also reported having questions about the availability of testing, how the testing was accomplished and the accuracy of the results. Furthermore, they had questions about what options would be available if both members of the couple were identified as CF carriers. Experience with Counseling and Testing
All subjects reported having a positive experience with genetic counseling. They reported that the counselor was knowledgeable and gave clear explanations. Subjects commented that pictures and diagrams used by the counselor were helpful. Subjects also reported that they had ample opportunity to ask questions and that their questions were answered; a few mentioned receiving a summary letter following counseling. Subjects expressed confidence in their genetic counselor; one man stated that the counselor made him feel "safer." The subjects saw the role of the genetic counselor as an educator, presenting information and options. They recognized the counselor's neu-
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trality in any decision making and thought that this was appropriate. The counselor helped identify important issues and questions that had not been raised. No subject reported being unduly anxious while waiting for the test result. Several mentioned that they were not anxious because the results came back within the expected time. Subjects reported that they learned their results either by telephone or letter and that this was appropriate. Given the opportunity to return for additional counseling after receiving the results, all but two couples declined. These couples attributed their declining further counseling to having the information they needed (carrier status) and not having additional questions. Notable exceptions were the couple who were both identified as gene carriers who returned for counseling to discuss reproductive options, and a woman who had not received counseling prior to testing. Reaction to Results
Subjects with a family history of CF reported that they were disappointed but not surprised to learn that they were CF gene carders. Their spouses' reactions were similar. With one exception, subjects did not report any long-term negative effects of learning that they or their spouse was a CF gene carrier. One female carrier described being "shocked and upset" upon learning her carrier status. She was uncertain about what to do next. She was concerned about the effect of being a CF carrier on her own health and wondered if she could develop CF in the future. This woman was engaged at the time of testing and felt that her carrier status may have contributed to the breakup of this relationship. She stated that her carrier status had "pushed her partner off" and "scared him." She mentioned that although it "eased his mind" to learn that they both needed to be carriers in order to have an affected child, they still broke up. It is of note that this woman did not receive genetic counseling prior to testing although she and her partner did have counseling after she learned the results of her testing. She told the interviewer that the counseling had helped resolve most of her questions and concerns. Understanding of Test Limitations
Subjects whose partners had a negative CF carder test reported being relieved to learn that the partner was most likely not a carrier. With few exceptions, the subjects understood the limitations of the carder testing. Expressions such as "low," "less than 1%," "virtually not a carrier," and
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"low, but no 100% guarantee" were used to describe the chance that a person with a negative test result could still be a CF gene carder. A few subjects responded even more specifically that the "test recognizes only 85% of CF genes" or that "the test could be wrong if the person carries a gene that could not be identified." Two subjects did not understand that a person with a negative mutation analysis still has a small chance of being a CF carder. In general, couples could accurately report their risk of having a child with CE A few stated that although they could not remember the exact number, they recall that the risk was "low" or "very low." Several volunteered that the risk seemed so low that they dismissed it altogether. Compared to the 1 in 4 risk for having a child affected with CF if they were both identified as carders this risk seemed inconsequential. Subjects also tended to compare the risk of having a child with CF to other risks, for example the general population risk for having a child with any birth defect. Reproductive Issues No subject reported any reproductive uncertainty as a result of the carrier testing. Although not asked about this directly, several subjects, mostly females, volunteered that they would not abort a pregnancy for CE One woman commented that she would have decided not to have children if both she and her husband were found to be CF carriers. Another woman commented that she worried during pregnancy that the test might have been wrong. One couple had both of their children tested for CF after delivery, even though they thought that their risk for having a child affected with CF was very low.
Other Concerns Several subjects expressed concern about their children's risk of being a CF gene carrier. A few mentioned their intention to tell their children about CF and to "have them tested." Subjects reported feeling disappointed and sad that their children would have to confront the issue of CF carder testing. Several had concerns and questions about the optimal timing for doing this. A few subjects raised concerns about the insurance implications of carrier testing, especially for their children, although no one had personally experienced any difficulties with this. No concerns were raised about employment discrimination.
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Subjects reported little difficulty sharing their test results with relatives. A few subjects, however, were reluctant to share the results with the parents of an affected relative. Generally, the women reported discussing carrier status more openly than the men. Recommendations for Others
Most subjects would recommend genetic counseling to others who had concerns about CF or other genetic conditions in the family, especially if they were planning on having children. When asked directly, subjects reported no disadvantages to CF carrier testing and described the value of the counseling and testing as providing knowledge and information and removing doubts.
DISCUSSION All of the participants in our study had requested genetic counseling and carrier testing themselves or specifically asked their doctor for a referral. They were also willing to participate in a focus group or be interviewed about their experience. Thus, they represent a group of individuals who were knowledgeable about CF and their carder risk and motivated to seek testing. Therefore, they may not be representative of all individuals with a family history of CE The reported positive experience with genetic counseling and CF carrier testing and the fact that few difficulties were encountered following testing may be due to factors such as a prior knowledge of CF, positive family adjustment to the diagnosis and family acceptance of genetic counseling in general. It is also possible that these subjects were more willing to talk about their experience because it had been positive. Several subjects raised concerns about their children's risk of being CF carriers. Questions were raised about whether and when to have the children tested. In this group of subjects there was no consensus about this issue. A few subjects also raised concerns about insurance implications of carrier testing, especially for their children. Most of our subjects requested testing because they were considering having a child. At the time of counseling the focus was generally on the potential risk of having a child affected with CE In our experience, couples rarely express any significant concern during counseling about the possibil-
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ity that their children will be CF gene carriers. Similarly, couples infrequently express concerns about the potential for insurance discrimination based on their or their children's carrier status. It is possible that these types of issues are more likely to emerge after counseling, especially for couples in which only one member is definitely identified as a CF gene carrier. There are limited data to guide genetic counselors on how to respond to these concerns (Billings, 1992). With the exception of the couple with both members who were identified as CF gene carriers and the unmarried woman who had not met with a genetic counselor prior to testing, the subjects elected not to return for additional counseling after learning their results. All couples who did not return for follow-up genetic counseling had counseling prior to testing; they reported having no additional questions or concerns upon learning their test results. It appears that genetic counseling prior to testing for individuals and couples with a positive family history of CF is a successful model for providing effective education and counseling. Subjects consistently reported a positive counseling experience and few difficulties upon learning their test results. The recent OTA survey of genetic counselors and nurses in genetics revealed that while many recognize the appropriateness of offering CF carrier screening to individuals with a positive family history, few counselors have routine contact with CF families. Although 55% of the survey participants responded that a CF Treatment Center exists at their institution, 86% reported that they do not provide genetic counseling through that facility. Furthermore, only 24% reported a large increase in the number of requests for CF carrier testing since the gene was isolated (U.S. Congress, Office of Technology Assessment, 1992b). At our institution genetic counseling is routinely provided for most parents of newly diagnosed CF children. The counseling includes a discussion of the carrier risks for relatives and the availability of accurate carrier testing. The family is encouraged to talk with their relatives about the risks and to have them contact the genetic counselor for more information. Despite these efforts we had only a small increase in requests for testing from relatives of affected individuals followed in our CF center. We recently completed a three year CF Carrier Screening Pilot Project in which we actively recruited subjects by requesting that CF patients (or their parents) provide us with information so that we could directly contact relatives to offer CF carrier testing. Approximately 54% of those contacted agreed to provide this information. Details of this study are reported elsewhere (Sorenson et al., 1994).
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In comparison to general population carder screening, testing relatives of affected individuals, or kinship-based testing, has several advantages. Individuals within a family have a higher prior risk of being o r d e r s . They also may have prior knowledge of and exposure to the disorder and therefore be more concerned and motivated to seek testing. It is important to develop efficient and effective models for providing CF carrier education and counseling for this population.
CONCLUSIONS This study employed focus group discussions and structured interviews to learn more about the experience of individuals who had requested CF carder testing and genetic counseling because of a positive family history of CE It was reassuring to learn that traditional genetic counseling appears to have been effective for this population. We were surprised to learn that for carriers, concerns about their children's carrier status and concerns about insurance implications of their carder status developed sometime after learning their results. Because most couples seek genetic counseling and carder testing for CF because of reproductive concerns, these issues might not routinely be addressed during the initial counseling. However, since many couples do not return for additional counseling after learning their test results it is important to address these issues at the time of the initial counseling. Genetic counselors strive to meet the needs of their clients by addressing their concerns and answering their questions. Focus groups and structured interviews are good techniques for identifying key issues to determine if current practices are meeting client needs.
ACKNOWLEDGMENTS The authors wish to thank A~yn McConkie-Rosell and Christina Ruiz for their help in recruiting subjects for this project. Supported in part by grant 5R01HG00643-02 from the National Center for Human Genome Research, Dr. Sorenson Principle Investigator.
REFERENCES Basch CE (1987) Focus group interview: An underutilized research technique for improving theory and practice in health education. Health Educ Quarterl 14(4):411-448.
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Beaudet AL (1990) Carrier screening for cystic fibrosis. Am J Hum Genet 47:603-605. Billings PR, Kohn MA, de Cuevas M, Beckwith J, Alper JS, and Natowiez MR (1992) Discrimination as a consequence of genetic testing. Am J Hum Genet 50:476-482. Boat "IT, Welsh MJ, Beaudet AL (1989) Cystic Fibrosis. In: Seriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic Basis of Inherited Disease. New York: McGraw Hill, pp 2649-2680. Caskey CT, Kaback MM, Beaudet, AL (1990) The American Society of Human Genetics Statement on cystic fibrosis screening. Am J Hum Genet 46:393. Sorenson JR, Cheuvront B, Brtming A, Talton S, DeVellis B, Koch G, Callanan N, Femald G (submitted) Proband and parent cooperation in an extended family cystic fibrosis carrier testing program. Am J Med Genet. U.S. Congress, Office of Technology Assessment (1992a) Cystic Fibrosis and DNA Tests: Implications of Carrier Screening. Washington, D.C.: US Government Printing Office. U.S. Congress, Office of Technology Assessment (1992b) Cystic Fibrosis and Genetic Screening: Policies, Practices and Attitudes of Genetic Counselors--Results of a Survey. Washington D.C.: US Government Printing Office. Weinblatt V (1993) Recommendations on Cystic Fibrosis Screening added to Society's Position Statements. Perspect Genet Counsel 15(2):9.
