Perceptions of reproductive risk and carrier testing among adolescent sisters of males with chronic granulomatous disease†
This article was prepared by a group consisting of both United States Government employees and non-United State Government employees, and as such is subject to 117 U.S.C.Sec.105.
Abstract
Although recent research has investigated the attitudes of parents, professionals, and adult siblings toward carrier testing of minors, no studies have focused on the experiences of minor siblings of individuals with X-linked and autosomal recessive conditions. To explore adolescent sisters' perceptions of their reproductive risks, attitudes toward carrier testing, and resources for information and support, we interviewed 14 parents and 9 sisters (ages 12–15) of males with chronic granulomatous disease (CGD), a primary immunodeficiency disorder inherited in both an X-linked recessive and autosomal recessive fashion. Our semistructured telephone interviews were audiotaped, transcribed, and subjected to template analysis (a common qualitative methodology). Girls were all aware that CGD is an inherited condition and each had made an assessment of her reproductive risk. All girls considered their parents to be their best source of information and support, but girls had trouble initiating discussions for fear of upsetting their parents. All girls and parents considered eventual carrier testing vital for reproductive decision-making and relationship-building. However, girls favored carrier testing at a later age and expressed more concerns about psychological risks associated with testing than did their parents. When faced with the hypothetical situation of being offered carrier testing “tomorrow,” half of the parents and untested daughters disagreed on the desirability of the test, with parents more likely to favor testing. Including adolescent sisters in family-based genetic counseling that provides an opportunity for age-appropriate discussion of inheritance and the timing, risks, and benefits of carrier testing would be beneficial to them. Published 2003 Wiley-Liss, Inc.
INTRODUCTION
Testing minors for carrier status of X-linked and autosomal recessive conditions is a controversial issue among parents, physicians, and genetics professionals that has generated considerable attention over the past 5 years. Professional organizations and policy-making bodies have published recommendations opposing childhood carrier testing, arguing that there are no proven psychosocial benefits to testing that outweigh the foreclosure of a child's autonomy and merit exposing a child to potential adverse psychological and social consequences of testing, including impaired self-esteem, stigmatization, and insurance or employment discrimination [Clarke, 1994; American Society of Human Genetics Board of Directors and the American College of Medical Genetics Board of Directors, 1995; World Health Organization, 1995; Task Force on Genetic Testing, 1997; Nelson et al., 2001].
Professional organizations and policy-making bodies have published recommendations opposing childhood carrier testing, arguing that there are no proven psychosocial benefits to testing that outweigh the foreclosure of a child's autonomy and merit exposing a child to potential adverse psychological and social consequences of testing, including impaired self-esteem, stigmatization, and insurance or employment discrimination.
Despite these positions, carrier testing for minors is available. A study of DNA diagnostic laboratories that requested the age of the patient showed that the majority had provided carrier testing to minors for fragile X syndrome, muscular dystrophy, adrenoleukodystrophy, hemophilia, and cystic fibrosis [Wertz and Reilly, 1997].
Parents often favor carrier testing of minors, arguing that the potential harms of carrier testing have been overstated and that parents have both the right and the ability to make decisions about carrier testing that are in their child's best interest.
Parents often favor carrier testing of minors, arguing that the potential harms of carrier testing have been overstated and that parents have both the right and the ability to make decisions about carrier testing that are in their child's best interest.
They contend that learning one's carrier status while young is beneficial as it allows parents to help children integrate carrier status into their identity [McConkie-Rosell et al., 1997, 1999; Gillott, 1998]. Parents seem to be acting on these beliefs and testing their children [Lavery, 1998; McConkie-Rosell et al., 1999].
What has been largely left out of this debate, despite publications emphasizing the need for research [Clarke, 1998; Michie and Marteau, 1998; Nelson et al., 2001], is the experiences and opinions of the minors most likely to be offered and undergo carrier testing: the siblings of individuals with X-linked and autosomal recessive conditions. Studies of adult sisters and brothers of individuals with cystic fibrosis, ataxia-telangiectasia, and X-linked severe combined immunodeficiency (SCID) have generated information regarding adult siblings' feelings about reproductive risks, carrier status, and carrier testing and have provided insight into family communication [Fanos and Johnson, 1995a, 1995b; Fanos, 1999; Fanos and Gatti, 1999; Fanos and Puck, 2001; Fanos et al., 2001], but only touched lightly on the experiences of adolescents retrospectively, from an adult perspective. Studies of adult siblings of individuals with Duchenne muscular dystrophy, hemophilia A, and aspartylglucosaminuria who were tested prior to age 18 indicate the majority were satisfied with carrier testing in childhood [Jarvinen et al., 1999a, 2000] and that their emotional, social, and physical wellbeing was not statistically different from that of controls [Jarvinen et al., 1999b, 2000]. Research into adolescents' attitudes toward carrier testing has been limited to individuals without a family history of a genetic condition who typically have little experience with the condition for which they are being tested [Childs et al., 1976; Decruyenaere et al., 1995; Welkenhuysen et al., 1996]. Without information on the experiences and attitudes of adolescent siblings, our ability to counsel them is compromised.
We developed a study to explore qualitatively the attitudes and experiences of adolescent sisters (ages 12–17) and parents of males with chronic granulomatous disease (CGD), a primary immunodeficiency disorder inherited in both an X-linked [gp91phox (Xp21.1)] and an autosomal recessive manner [p47phox (7q11.23), p67phox (1q25), p22phox (16p23)] [Malech and Nauseef, 1997]. CGD was chosen to allow us to explore the experiences of sisters in families with the same disease but different modes of inheritance. Brothers were not interviewed because carrier testing for them is relevant only in autosomal recessive families. CGD is a rare condition (incidence, 1/200,000) characterized by recurrent life-threatening infections, with the skin, lungs, bone, lymph nodes, and liver particularly susceptible to infections [Winkelstein et al., 2000]. Mortality in CGD is 2–5% per year, concentrated in young children [Malech and Nauseef, 1997; Winkelstein et al., 2000]. Biochemical carrier testing is available, and in families in which the mutation is known, carrier testing can be performed on a molecular basis. The aims of the study were to explore adolescent sisters' understanding of the genetic nature of CGD in their family, to explore sisters' and parents' attitudes toward CGD carrier testing, and to explore sisters' resources for information and support.
MATERIALS AND METHODS
Recruitment
The study population was drawn from two sources: participants in NIH Clinical Center studies on CGD and enrollees in the Registry of U.S. Residents Affected by Chronic Granulomatous Disease of the Immune Deficiency Foundation. Since members of the registry may only be contacted through the physician who enrolled them, we mailed letters requesting the enrolling physician's assistance in inviting their patients to participate in our study by either obtaining permission from the families for us to contact them directly or forwarding letters of invitation we had enclosed (Fig. 1). The letters of invitation were accompanied by a family response form for families to return, indicating their interest in participating and providing information that allowed us to determine eligibility.
Recruitment process.
Participants or parents of participants in intramural NIH CGD research were directly mailed letters of invitation accompanied by a family response form. Nonrespondents were mailed reminder letters 3 weeks after the initial mailing (Fig. 1).
Responding families that included an adolescent sister (aged 12–17) of at least one male (living or deceased) with CGD were called and asked if they would be willing to be interviewed. Those expressing interest were sent consent forms for adults and assent forms for minors. If a consent form had not been received within 3–4 weeks of mailing, a follow-up telephone call was made. If the forms were not returned within 6–8 weeks, a second set of forms was mailed. Upon receipt of completed forms interviews were scheduled.
Interviews
One of the investigators (C.A.J.) conducted semistructured interviews that ranged from 20 to 90 minutes. Interview topics included family and medical history of CGD, impact of the diagnosis and disease on the family, perceptions of the genetics of CGD, perceptions of the girl's reproductive risks, attitudes toward and experiences with carrier testing of minors, and family communication about CGD. Prenatal diagnosis and selective termination of pregnancy were not discussed. The interviews were tailored for type of participant (father, mother, sister) and some flexibility was allowed to enable participants to discuss topics of particular interest and to account for specific family experiences, but each topic in the guide was discussed with each participant. Prior to interviewing an adolescent girl at least one parent was interviewed. At the end of the parents' interviews, we described the questions we would be asking their daughter and gave the parent the option to eliminate questions they felt were inappropriate or problematic for their daughter. No questions were eliminated through this process. In order to minimize anxiety for the adolescent interviewees, we posed questions we anticipated to be sensitive, as what advice they would give to another sister prior to asking how the topic affected them.
Analysis
Audiotapes of the interviews were transcribed and subjected to template analysis, a commonly used qualitative analysis methodology [Crabtree and Miller, 1992]. As is customary in template analysis, prior to conducting interviews a code book was developed that contained codes for anticipated responses derived from and based on prior research and existing theories on adolescent development. Upon reading transcripts from the interviews, these codes were modified and expanded to better incorporate the data. Each transcript was coded by two of the investigators (C.A.J. and D.W.H.) independently. Following the initial coding, the investigators met to discuss any inconsistencies in coding and the sufficiency of the code book. Through an iterative process we developed a final code book with which the transcripts were coded. After the coding was finalized, we entered the codes into NUD*IST, a qualitative analysis program that facilitates the grouping of similarly coded text. Responses to questions about the best age for carrier testing were divided into categories of under age 18 or as an adult and tested for association with type of respondent (parent or girl) using the chi-square test.
RESULTS
Response Rates
Seventy-six percent (67/88) of registry physicians agreed to invite their patients to participate in the study. Physicians reported that 39 patients (21.5%) had been lost to follow-up. They also chose not to contact 23 (12.6%). They forwarded our invitation letter to 109 patients (59.9%) and indicated we should contact 11 (6.0%) directly. The most common reason given for choosing not to contact a family was that the affected individual was deceased. Physicians also sent invitations to or gave us permission to contact an additional eight families they had not yet enrolled in the registry. Among the 128 parents or patients contacted, 52 (40.6%) mailed back the family response form expressing interest in participating.
Of the 102 patients or parents of patients enrolled in NIH protocols on CGD who had not already responded to our invitation through their enrollment in the CGD registry, 53 (52.0%) mailed back a family response form indicating interest in participating. Of the 105 interested respondents, 14 families included an adolescent sister of an affected male and were therefore eligible to take part in the interviews. Three of these families did not return informed consent forms and one family declined the interview.
Description of Participants
We interviewed 23 individuals in l0 families (10 mothers, 4 fathers, 9 adolescent sisters). The adolescent sisters in two families did not participate. The mother of one 12-year-old who had lost a brother to CGD did not think her daughter was emotionally ready for an interview. Another 16-year-old sister lived separately from her mother and, according to the latter, refused to participate on account of familial conflict. As noted in Table I, none of the girls who participated were known to be carriers.
| Participating families (n = 10) | |
| Mode of inheritance | |
| X-linked | 7 (70%) |
| Likely X-linked | 1 (10%) |
| Autosomal recessive | 2 (20%) |
| Child/children with CGDa | |
| Living | 8 (80%) |
| Deceased | 3 (30%) |
| Male | 11 (100%) |
| Female | 0 (0%) |
| Race/ethnicity | |
| Caucasian | 8 (80%) |
| African American | 2 (20%) |
| Participating adolescents (n = 9) | |
| Age | |
| 12 | 2 (22%) |
| 13 | 2 (22%) |
| 14 | 2 (22%) |
| 15 | 3 (33%) |
| Affected sibling(s)a | |
| Younger | 6 (67%) |
| Older | 4 (44%) |
| Living | 8 (89%) |
| Deceased | 2 (22%) |
| Carrier status | |
| Carrier | 0 (0%) |
| Not a carrier | 3 (33%) |
| Unknown | 6 (67%) |
- a One family had two sons with CGD (one living, one deceased).
Understanding of Inheritance and Reproductive Risks
Inheritance of CGD
The girls we interviewed were all (9/9) aware that CGD is inherited. Most had a correct basic understanding of how CGD was inherited in their family. Almost all understood that unless a person was a carrier it was unlikely that they would have an affected child. Examples of how girls expressed their understanding follow.
“[My mom] says that she's a carrier and that it was passed down from her mom … and sometimes she'll say, well, you know, you could possibly be a carrier. … My mom had passed it on to my brother, and that's how he got it” (2002; age 12; X-linked).
“My brother got CGD when his dad and his mom—they don't have it, but when they gave him his genes, when they mixed together, it made CGD” (2035; age 13; autosomal).
Some girls were confused about how CGD was inherited. Parents that were most confused about the inheritance of CGD had daughters who were similarly uncertain.
Personal reproductive risks
All the girls (9/9) had thought about the possibility of having a child with CGD and each had made an assessment of her reproductive risk. The girls did not consider what they knew about the inheritance of CGD to arrive at a conclusion about their reproductive risk. Rather, they based their responses on family experience with CGD, gut feelings, and, in three cases, the results of carrier testing.
All the girls had thought about the possibility of having a child with CGD and each had made an assessment of her reproductive risk. The girls did not consider what they knew about the inheritance of CGD to arrive at a conclusion about their reproductive risk. Rather, they based their responses on family experience with CGD, gut feelings, and, in three cases, the results of carrier testing.
Three of six girls who did not know whether they were carriers guessed about their carrier status and likelihood of having an affected child based on their family's experiences with CGD.
“I guess I'd say it [being a carrier] is pretty likely. Because I don't think it's just going to skip me. And I figure if my grandmother had it and she passed it on to her son, and my mom had it and she passed it on to my brother, then it's pretty likely that I may pass it on to my kids” (2002; 12 years old; X-linked).
“I think I might [be a carrier] because my mom every now and then says, like, carriers do get little symptoms. … I think there could be a higher chance [of being a carrier] since I do have some other symptoms. … I think my [chance of having a child with CGD] is more in the line of a 50-50 chance, because, like, my mom's mother is a carrier and she had five kids, three girls, and two boys, and the two boys they didn't get it and my mom was the only one that is a carrier, so there is a possibility that if I am a carrier, and I do have a boy, that he won't get it” (2061A; age 13; X-linked).
The three other girls who did not know whether they were carriers acknowledged their uncertainty but still estimated their reproductive risks. The three girls who knew they were not carriers understood they had an extremely small chance of having an affected child.
Implications of reproductive risks
Some of the girls struggled with whether they would have children if they were carriers. A girl who didn't know her carrier status contemplated: “Hopefully I'm not a carrier for my kids and I don't have to worry about passing it on. … If I am I know that's going to be in the back of my mind that, you know, possibly it's going to get on to my kids. But I'm not going to let that affect when, if I do have kids. I mean, I know that I don't want to see [a child] go though pain like that, but I know that I can't totally block off the idea of having kids” (2002; age 12; X-linked).
Other girls thought carrier status would not affect their reproductive decision-making but worried about practical aspects of having a child with CGD, including the impact an affected child would have on healthy siblings: “I worry if I am a carrier, too, because then my son could possibly get it and it would be kind of like a complication—I'd have to deal with a son being sick all the time. … I would have to be really careful and cautious and it might be kind of hard if I had other children, too. My mother knows a lot—she's a nurse, so she knows a lot about how to take care of him [her brother] and stuff, and I would be, like, afraid I wouldn't really know how, like what to do to take care of him” (2061B; age 15; X-linked).
For three girls, having a family was a decision for the remote future: “I'm not too fond about having children. … I'm kind of like the person that would go to school for 10 years, then try to work from there” (2035; age 13; autosomal).
Attitudes Toward Carrier Testing
Parents and girls universally believed carrier testing was important for reproductive decision-making, preparing for the future, and being honest in building romantic relationships. All untested girls wanted to have carrier testing someday, and all parents thought carrier testing was important for their daughters. However, there was considerable variability in what participants believed to be the appropriate age for carrier testing. Girls favored carrier testing at an older age than parents (Table II).
| Best age for carrier testing | Parents (n = 14) | Girls (n = 9)a |
|---|---|---|
| As young as possible | 4 (29%) | 0 (0%) |
| Puberty | 8 (57%) | 3 (33%) |
| Mildteens | 1 (7%) | 1 (11%) |
| Eighteen or olderb | 1 (7%) | 4 (44%) |
- a One girl thought there was no ideal age for testing.
- b Parents were significantly more likely than girls to favor carrier testing before age 18 (P < 0.05).
Risks and benefits of carrier testing: parents
The age for carrier testing favored by parents was associated with their perceptions of the risks and benefits of carrier testing. Parents who favored testing prior to adolescence believed that health information is important and a good parent should know as much as possible and that it is to the emotional benefit of the child to grow up knowing their carrier status.
“I would want to offer [information about carrier status] as part of my upbringing and as part of ensuring their mental … wellbeing. Knowing that [carrier status] at 18, it's like finding out you're adopted at 18. I would want to cultivate a positive attitude about that news as early as possible” (2035; mother; autosomal).
Parents who favored carrier testing around puberty or during the teen years thought the following:
• One, it was vital that a girl know her carrier status before becoming sexually active. Some parents though that knowing her carrier status would enable a girl to make better choices about being sexually active.
“If a girl knows that at 14—'hey, I could get mixed up with the wrong guy and end up with a child of my own, like my brother'—maybe she would think twice, you know” (245; mother; autosomal).
• Two, at this age many girls are mature enough to understand both intellectually and emotionally the meaning of test results.
“I'm thinking that the perfect age might be when a child starts menstruating, because there's so many different things going on at that time … they're more of a woman now and not a child. They're getting emotionally ready to hear those things” (190; mother; X-linked).
• Three, adolescents have the right to know their carrier status.
“They grow up with CGD in the family; it's their right to know whether they are carriers” (2061; mother; X-linked).
• Four, although there could be psychological risks of testing, the benefits of knowing carrier status supercede this risk.
“It may make [my daughters] feel inferior in some way, that they have this thing inside them … without really knowing or understanding what that is. On the upside, I think it gives them a chance to get more educated” (2061; father; X-linked).
The mother who believed carrier testing of minors was inappropriate considered the emotional risks to testing substantial.
Risks and benefits of carrier testing: adolescents
Like their parents, many of the girls believed it was important that adolescents have access to carrier testing for reproductive decision-making. Unlike their parents, they believed this was only important if a girl was sexually active or actively planning children.
“No one needs to be having a kid before 18 anyway … but if they're going to ‘do it’ [have sex] at that age, I think that it [carrier testing] should be made available. … If they weren't ‘doing it,’ I don't see why it shouldn't be, like, past 18” (245; age 14; autosomal).
“Some girls, you know, when they graduate they could not want to go to college or she might want to start a family right away. … She could still find out after she's 18, but she might want to find out before if she wants to get pregnant” (371; age 14; X-linked).
Girls were more cognizant of the potential psychological risks of carrier testing, particularly if done at a young age, than were their parents. Even the girls who believed carrier testing of minors is appropriate expressed more concerns about the potential psychosocial risks of testing than did their parents.
Girls were more cognizant of the potential psychological risks of carrier testing, particularly if done at a young age, than were their parents. Even the girls who believed carrier testing of minors is appropriate expressed more concerns about the potential psychosocial risks of testing than did their parents.
The girls believed that carrier testing, particularly at a young age, can create a lot of worry and stigma and can negatively alter plans for the future.
“I don't think they should do it when they are real young. I think about my age [15] or so would kind of be good … if, like, they are young and they found out about it then, they will worry about it a whole lot” (71; age 15; likely X-linked).
“Some kids might overreact, worry a lot” (2061A; age 13; X-linked).
“Other girls my age, if they found out they were a carrier they might worry about it, and they would be afraid to have kids” (2061B; age 15; X-linked).
“Around 18, because when you're younger it's probably harder to take the news and you'd be worried about ever having a husband because you'd be [like], ‘Oh, what would he think if we had a child like that? Would he still like me?’” (190; age 12; X-linked).
Girls' desire to have carrier testing
All but one of the girls who did not know her carrier status had very clear ideas on whether she would want testing were it hypothetically offered “tomorrow”; two of the six girls who had not been tested (both 12-year-olds) would definitely not want testing yet for fear of it being stigmatizing or emotionally overwhelming. In addition to being the youngest participants, these girls were also the only two who had lost brothers to CGD.
“Not really at this age. I'd probably want to wait until I'm older. I'd probably be able to understand it more. … [Also], you should really think about your relationships with people. You might be telling your family about it, that you're positive. And younger siblings [of which she has three] when they say stuff, they're not really sure what they're saying, they might just be repeating things they've heard. If you have friends over and they say that, it could make your relationships sort of uncomfortable with people who know you have this thing that affects you” (190; age 12; X-linked).
Conversely, three of six untested girls would definitely want carrier testing, mostly because they have been thinking about their carrier status, believe it has relevance for their future, believe they can handle the results emotionally, and would like to have an answer. These three girls all identified potential risks of carrier testing, but felt these risks were not substantial for them.
“I want to find out, kind of to be prepared. It's something to think about for the future. It's just being able to find out if there is a possibility [of having a child with CGD]” (71; age 15; likely X-linked).
One 14-year-old did not know whether she would be interested in testing since the prospect of having children was remote to her.
Discordance between parents' and girls' attitudes
Among the nine parents of the six girls who had not undergone carrier testing, four had discordant views from their daughters about whether it would be desirable for the girl to have carrier testing were it hypothetically offered tomorrow. Of the four parents of the two girls who said they would not want to be tested, one mother would want her daughter to be tested. One mother (of two) of the three girls who would want testing tomorrow, were it hypothetically offered, would not want her daughters tested as minors due to concerns about insurance discrimination. Both parents of the girl who was unsure whether she would want carrier testing strongly favored it.
The nine parents made 11 predictions (2 each for the couple with two daughters) about whether their daughters would want carrier testing prior to age 18. Five of these predictions (four made by fathers) were incorrect. In four cases, parents predicted their daughters would be interested in carrier testing during adolescence when the girls said they would not.
One father believed: “I would think she would [want carrier testing], yes. She's an extrovert to start with, and she's not bashful about those things. And I think she'd want to know once she understood the magnitude of being a carrier and what it could mean to her in the long run” (2002; father; X-linked).
His daughter understood the implications of being a carrier and because of that was concerned that a positive test result would be overwhelming: “I want to know for myself, but I don't think I want to know now. I don't want it to overpower my life. I don't want to stay up nights thinking, you know, okay, from this point on I'm not going to have kids. … I want to know eventually but I don't think I want to know now. I don't want to think of it like that. I don't want to think about it at school and worrying all day long” (2002; age 12; X-linked).
In one case, a father believed his daughter would have no interest in testing when she did.
Sources of Information and Support
Communicating with parents
The girls believed their parents, particularly their mothers, were their best sources for information and support. However, some had concerns about upsetting their parents with questions and had difficulties communicating with their parents during emotionally stressful times. One girl whose brother died from CGD described the conflict she experienced when deciding whether to discuss CGD with her parents:
“I don't want to say weird, but it's a different position when you're trying to talk about it. Like, if I try and bring it up, I just don't want to make my parents, I guess, sad. And I don't want them to think back to the bad times when he was in the hospital and what they were going through. But I guess it's okay for me to talk to my parents. It's not like they'd get mad … it's not like I can't talk to them about it but it's definitely hard to ask them questions about it. … I know they're there and I know that they're open to anything that I have to ask them or I have to say about it but it's just hard because they get upset and I just don't like seeing that” (2002; age 12; X-linked).
Despite these difficulties, girls were confident their mothers understood CGD and could accurately answer any questions they might have. They also thought that their parents' experience dealing with CGD and knowledge of the girls themselves made them capable of providing emotional support.
Communicating with peers
The girls were skeptical about the value of talking to their peers. They were particularly concerned about the potential for stigmatization resulting from such conversations.
“If you tell the wrong people they'll just spread it and then everybody will know. … It would be spread around and it's like, ‘Oh, stay away!’ … because they don't quite understand the disease yet and I'm sure you wouldn't either. So, you can't go telling, like, all your friends” (245; age 14; autosomal).
“Make sure you're talking to an open-minded person … [otherwise] they'll probably make fun of you, like, ‘Ooh, your brother is this’ and he is that” (2102; age 15; X-linked).
“Well, like, with friends at school or kids in the classroom, you shouldn't really talk about [it] very much, because you don't know if they might go blabbing off to kids and you might be teased” (190; age 12; X-linked).
Girls also doubted that their peers had sufficient information about CGD or experiences with chronic illness to understand their feelings.
Communicating with health professionals
The girls considered doctors good sources of information about CGD. Many said they would suggest that another sister with questions about CGD ask her brother's doctor about them. However, few had actually talked to a physician or another health professional about CGD.
DISCUSSION
This is the first study investigating how adolescent siblings of individuals with an inherited condition view their reproductive risks, options for carrier testing, and resources for information and support regarding these issues. Many of our findings are consistent with those of others, but ours elicited minors' views directly.
Perception of Reproductive Risk
Siblings of individuals with a chronic illness begin to worry about whether they will have children with the same disease as their sibling when they start to conceptualize severe illness and disability as having external causality, typically around age 10 [Powell and Ogle, 1985; Wertz et al., 1994].
Siblings of individuals with a chronic illness begin to worry about whether they will have children with the same disease as their sibling when they start to conceptualize severe illness and disability as having external causality, typically around age 10.
Thus, our interviewees, who had all considered reproductive risks, had likely been thinking about their chances of someday having a child with CGD for several years. Family experiences with a genetic disorder and the proportion of affected individuals in a family influence risk perception among adults [Shiloh and Saxe, 1989; Palmer and Sainfort, 1993]. Based on our findings, these factors appear to have a similar influence on the perception of adolescent sisters. The development of “gut feelings” in approximately half of the girls about their carrier status is similar to what adult siblings of individuals with cystic fibrosis and X-linked SCID have reported [Fanos, 1997; Fanos et al., 2001].
Our interviewees' concerns about stigmatization appear to be the basis for their reluctance to discuss CGD with their peers. Due to the premium placed on interpersonal desirability during adolescence, teenagers may also be especially likely to feel stigmatized by a positive carrier test.
Attitudes Toward Carrier Testing
Parents' reasons for supporting testing prior to age 18 were similar to the most frequently cited reasons for carrier testing of children [Fanos and Mackintosh, 1999; McConkie-Rosell et al., 1999; Fanos et al., 2001]. Parents' less frequent concerns about psychological and social risks associated with testing were also consistent with past findings [McConkie-Rosell et al., 1997, 1999]. In this study, we queried only adults who are currently parents of unaffected adolescent girls and are therefore actually faced with the prospect of their daughters' reproductive risks and the possibility of carrier testing.
Adolescent sisters' concerns about carrier testing—that it will cause anxiety and stigmatization and negatively alter their plans for the future—are among the potential harms identified by the American Society of Human Genetics/American College of Medical Genetics report on the implications of genetic testing in children and adolescents [American Society of Human Genetics Board of Directors and the American College of Medical Genetics Board of Directors, 1995]. The girls' concerns that a positive carrier test result could create anxiety may be well founded. In a study of adolescents who had undergone population screening for Tay-Sachs carrier status, nearly half of carriers were worried about their heterozygosity following disclosure of their test results [Childs et al., 1976], and 20% of carriers were still worried 8 years later [Zeesman et al., 1984]. A retrospective study of young adults who had undergone carrier testing for either Duchenne muscular dystrophy or hemophilia A prior to age 18 reported that about two-thirds of carriers and individuals with inconclusive results were worried about the test results [Jarvinen et al., 1999b].
The interviewees' concerns about stigmatization are also valid. Stigmatization, defined as a societally constructed perception of “undesired differentness” [Goffman, 1963], is a common experience among families with a member who has a chronic illness or disability. As adolescence is a time when conformity is a prerequisite to peer group membership [Hofmann, 1997], adolescent siblings are particularly susceptible to stigmatization [Powell and Ogle, 1985]. Our interviewees' concerns about stigmatization appear to be the basis for their reluctance to discuss CGD with their peers. Due to the premium placed on interpersonal desirability during adolescence [Hofmann, 1997], teenagers may also be especially likely to feel stigmatized by a positive carrier test. Even adult siblings have perceived themselves as less desirable as a mate due to their carrier status [Fanos and Puck, 2001].
That the girls were able to think through the implications of carrier testing and provide an opinion about whether they would want it is consistent with adolescent intellectual development. The capacity for abstract reasoning emerges around age 11–12 and improves during the next few years as adolescents become increasingly able to imagine hypothetical situations and make logical deductions [Petersen and Leffert, 1995]. At this age, children begin to be able to understand the implications of genetic testing [Wertz et al., 1994]. By around age 14, decision-making and reasoning ability is as good as that seen in adulthood. However, adolescents may make different decisions from adults in a similar situation because adolescents may be aware of different consequences or weigh consequences differently than adults [Petersen and Leffert, 1995]. Although the older adolescents we interviewed presumably had a reasoning ability comparable to that of their parents, they frequently held discordant opinions from their parents about whether it was desirable for them to have carrier testing. This discordance was likely partially the result of parents and girls considering the risks and benefits of testing differently.
Resources for Information and Support
In families with seriously ill children, communication about the disease and its implications tends to be limited [Fanos, 1997]. Secrecy seems particularly pervasive when the illness has a genetic etiology and parental guilt and blame over the transmission of the illness and the desire to protect siblings from painful information hamper discussion [Fitzpatrick and Barry, 1986; Fanos and Johnson, 1995b; Fanos, 1999; Fanos and Puck, 2001].
In families with seriously ill children, communication about the disease and its implications tends to be limited. Secrecy seems particularly pervasive when the illness has a genetic etiology and parental guilt and blame over the transmission of the illness and the desire to protect siblings from painful information hamper discussion.
Although some girls had difficulty initiating conversations, our interviewees discussed CGD with family members. In contrast to other genetic conditions about which family communication has been studied (Duchenne muscular dystrophy, cystic fibrosis, and X-linked SCID at the time), CGD is not perceived by most parents as a terminal progressive condition. Instead, parents thought it possible for their son to have a reasonably healthy adulthood. Perhaps these parents therefore feel less of a need to protect their healthy children from information about the disease. Additionally, preventive behavioral measures can be taken to decrease the chance a person with CGD will get seriously ill. Parents often enlisted the aid of older sisters in ensuring their affected son(s) was not exposed to nonchlorinated water, mulch, leaves, etc. In order to do this, parents needed to discuss CGD with their daughters.
Study Limitations
The findings of this study are limited by several factors. While having a sufficiently large population to enable the researcher to draw statistically significant conclusions is not relevant to qualitative research, it is important to have enough interviewees to cover the range of experiences of individuals in the population of interest. This point is reached when no new themes are uncovered in the interviews, a situation known as saturation. While saturation was reached for the parents, it was not for the adolescent interviewees, possibly because of their range of ages and carrier testing experiences. Additionally, it is possible that the families who participated are different in some way from those who did not. Participants may have been more comfortable discussing CGD with their daughters, resulting in the girls' having a better understanding of their reproductive risks than girls in nonrespondent families. Finally, untested girls and parents were asked whether they would want testing were it hypothetically offered tomorrow. Their responses may not reflect the choices they would make if actually offered carrier testing.
Recommendations
The results of this study strongly support the inclusion of adolescent sisters of those with CGD in genetic counseling sessions and provide insight into how such sessions may be effectively conducted. The results also provide insight into the basis for policy-making regarding carrier testing for adolescent sisters of those with CGD and other X-linked and autosomal recessive conditions. Based on the results of this study, we make the following recommendations.
One, including adolescent sisters in a genetic counseling session integrating a discussion of their perceptions of their reproductive risks, their family experiences, and information about how CGD is inherited in their families would be beneficial. As adolescents have typically entered the stage of abstract thought, most will be able to understand basic information about their reproductive risks. Since girls have thought about their reproductive risks, it is unlikely such a session would cause a girl to be faced with an issue she has never considered before.
Two, as the girls viewed their parents as good sources of information and support and believed talking to health professional might be helpful, a joint genetic counseling session with parents and girls may be appropriate. Facilitating a discussion between parents and daughters during a genetic counseling session could provide a model for future conversations within the family about the daughter's reproductive risks and her options for testing.
Three, as most girls held strong opinions about whether they were currently interested in carrier testing and were capable of understanding the nature of carrier testing, discussion of carrier testing is appropriate for most adolescent girls and actual testing may be appropriate for some. Due to potential psychological risks (identified by the adolescents themselves), testing should not be undertaken without substantial discussion and consideration. It may be useful for the genetic counselor or physician to have ongoing discussions with the family about the timing, risks, and benefits of carrier testing.
Four, a private counseling session with an adolescent without her parents present may be important. Under no circumstances should adolescents be tested without an independent opportunity to explore the meaning of test results and voice questions and concerns. Girls and their parents frequently hold discordant opinions about the desirability of testing and have different perceptions of its risks and benefits. While girls' reliance on their parents, particularly their mothers, for information and support is beneficial in other areas, it probably increases the chance that adolescent girls will be unduly influenced by their mothers' opinions. Although girls' opinions may change with development and life experience, their concerns about carrier testing creating anxiety and stigmatization are valid and should be respected.
Acknowledgements
The authors thank Drs. Jerry Winkelstein and Katherine DeVet of Johns Hopkins University for generously sharing their wealth of experience that guided development of the study; Drs. Harry Malech, Steve Holland, and John Gallin of the National Institute of Allergy and Infectious Diseases for inviting their patients to participate in the study and providing technical information about carrier testing for CGD; Ms. Barbara Biesecker of the National Human Genome Research Institute for providing advice throughout the study; the Immune Deficiency Foundation for allowing us to use their Registry of U.S. Residents Affected by Chronic Granulomatous Disease; as well as the parents and girls who were so gracious in sharing their experiences and opinions.
