Effect of family history on disclosure patterns of cystic fibrosis carrier status

INTRODUCTION

Historically, most reproductive genetic risk counseling for cystic fibrosis (CF) was offered based on family history. In the early 1990s, CF mutation analysis became available to individuals with a family history, and since the late 1990s, genetic carrier testing has been available to a wider population. In 1997, a National Institutes of Health (NIH) consensus statement recommended offering CF carrier screening to Caucasian individuals of reproductive age regardless of family history [National Institutes of Health, 1997]. In 2001, the American College of Obstetrics and Gynecology (ACOG) and the American College of Medical Genetics (ACMG) jointly issued a similar recommendation [American College of Obstetrics and Gynecology and American College of Medical Genetics, 2001; Grody et al., 2001].

One of the main barriers to carrier testing is lack of public awareness about CF and what CF carrier testing can and cannot do.

One of the main barriers to carrier testing is lack of public awareness about CF and what CF carrier testing can and cannot do.

While the consensus statements seek to detect CF carriers in the general population, first- and second-degree relatives of those already known to be CF carriers are themselves at higher risk of being carriers. In order to counsel these patients accurately about their risk of being a CF carrier, they must be aware of their relative's CF carrier status and inform the clinician of this information. Barriers to information dissemination include lack of information about CF [Suhr et al., 1994; Fanos and Johnson, 1995a]; the perception that relatives would not be interested in carrier screening [Suhr et al., 1994; Sorenson et al., 1996; Williams and Schutte, 1997]; and gender (studies show that men are less likely than women to inform family members of their genetic risks [Callanan et al., 1995; Fanos and Johnson, 1995a]).

Even when individuals know that they are at increased risk for carrying a genetic abnormality, many choose not to undergo testing. In studies that assess individuals at risk for carrying a disease mutation or a balanced chromosome translocation based on family history, testing uptake has been low [Ayme et al., 1993; Suhr et al., 1994], and first-degree relatives are significantly more likely to undergo carrier testing than more distant (second- and third-degree) relatives [Suslak et al., 1985]. Studies that specifically addressed the interest in and acceptance of CF screening in individuals with a family history of CF [Callanan et al., 1995; Sorenson et al., 1997; Henneman et al., 2001] and in nonpregnant individuals in the general population [Clayton et al., 1996] demonstrate significantly lower screening uptake by individuals without a family history of CF.

Studies that specifically addressed the interest in and acceptance of CF screening in individuals with a family history of CF and in nonpregnant individuals in the general population demonstrate significantly lower screening uptake by individuals without a family history of CF.

Awareness of and personal experience with CF has been associated with both increased [Sorenson et al., 1997; Wake et al., 1997] and decreased [Botkin and Alemagno, 1992] uptake of carrier screening, suggesting that the perceived burden of CF may play a role in whether testing is pursued [Fanos and Johnson, 1995b]. There may also be logistical barriers to uptake of testing such as cost, accessibility to facilities offering testing, the desire to avoid phlebotomy, and family myths about who is at risk for carrying a disease mutation [Suhr et al., 1994; Fanos and Johnson, 1995b; Clayton et al., 1996; Sorenson et al., 1997].

Given the current NIH, ACMG, and ACOG recommendations, more CF carriers without a family history are likely to be detected. Our study addresses whether the presence of a family history of CF affects carrier status information dissemination patterns and the uptake of carrier testing in at-risk relatives; and which factors facilitate or hinder information dissemination.

MATERIALS AND METHODS

RESULTS

Thirty-five surveys were returned from group A (parents of children with CF), with five responses excluded because either a parent (n = 2) or the affected child (n = 2) was adopted, or because the survey was not adequately completed (n = 1). The total response rate was 30/95 (33%). For group B, 51 surveys were sent, but 3 surveys were returned as undeliverable. Of the remaining 48, 18 were returned (38%). Therefore, a total of 48 valid surveys make up the study data: 30 from group A (family history of an individual affected with CF) and 18 from group B (no family history of an individual affected with CF).

Subject demographics are reported in Table II. There were no significant differences between the two groups with regards to age, gender, or percent in a married or committed relationship. There were, however, significant differences between the groups with regards to educational level and religious affiliation. With regards to education, 85% of the overall population had at least a college education, with fewer in group A reporting college education or higher (t-test, P = 0.001). Religious affiliation was notable for a high percentage of group B reporting Jewish affiliation (∼65%), while group A was almost exclusively of Christian affiliation, with no respondents of Jewish descent.

Consistent with our study design, 100% of group A reported knowing someone affected with CF; somewhat surprisingly, no individual in the general population screening group knew anyone with CF (chi-square, P < 0.001). On a Likert scale of 1 (not severe) to 4 (severe), 48% of respondents stated that CF was severe, 30% moderate, 18% mild, and 2% not severe. There were significant differences between groups such that all individuals in group B (who did not know an individual with CF) ranked CF as moderate to severe (mean, 3.71), while individuals in group A, with a family history of CF, reported a broader range of perceived severity (mean, 3.00; ANOVA, P = 0.004). Because of the direct association between group affiliation and knowledge of a person affected with CF, it was impossible to determine whether the family history or overall knowledge of CF was the major factor underlying the difference in perceived severity of CF.

Seventy percent of respondents stated they would consider prenatal diagnosis for CF; 6% stated they were against it; 14% stated that testing should be available, although they would not undergo testing themselves; 8% were undecided about prenatal diagnosis for CF; and 2% had not thought about it. There were significant differences between groups, with 100% of the general population screening group stating that they would consider prenatal diagnosis for CF, versus approximately 50% of the obligate carrier group (P = 0.004).

DISCUSSION

There are numerous reasons why some carriers of genetic abnormalities do not share carrier information: altered self-concept [McConkie Rosell and DeVellis, 2000], misunderstanding of genetic risk, the perception that their relatives would not be interested in undergoing genetic testing [Surh et al., 1994; Sorenseon et al., 1996], or because of their own personal feelings about disease severity and/or about the use of testing and prenatal diagnosis.

There are numerous reasons why some carriers of genetic abnormalities do not share carrier information: altered self-concept, misunderstanding of genetic risk, the perception that their relatives would not be interested in the information, or because of their own personal feelings about disease severity and/or about the use of testing and prenatal diagnosis.

Studies that address the psychosocial aspects of carrier status focus primarily on self-concept and do not necessarily measure how disclosing carrier status impacts family dynamics. It is likely that such disclosures alter family relationships in both positive and negative ways, which also may vary depending on the mode of inheritance (e.g., autosomal recessive vs. sex-linked vs. translocations).

Our study indicates that in both groups CF carriers are more likely to share information about their carrier status with those relatives who are more closely related genetically and with those relatives with whom there is a close social bond; CF carriers favor telling one side of the family (more often the maternal relatives than paternal ones) of their status, suggesting personal or social factors play a greater role in motivating carriers to share their status than genetic factors; and disclosure of carrier status usually occurs within 6 months of receiving the diagnosis of being a carrier, often in the context of explaining an affected child's condition or as a means of soliciting social support. Individuals with a family history of CF (e.g., an affected child) are more likely to share carrier status with relatives of all degrees, primarily because they are sharing other health information about their child.

Even if one assumes some selection bias, i.e., those individuals returning questionnaires were more comfortable with sharing their carrier status, it is clear from our study that the presence of an affected family member significantly influences the disclosure pattern of CF carrier status within the family. Yet the method of identifying CF carrier status does not impact the risk assessment; relatives of CF carriers, whether identified via general population screening or due to a positive family history, have the same risks (e.g., a third-degree relative to a CF carrier has a one-in-eight chance of also being a carrier, regardless of whether there is an affected individual in the family). While this may become less significant as CF carrier screening becomes routine in the prenatal setting, it does prevent fully informed decision-making for those who do not seek counseling or testing prior to conception. Thus, without knowledge of a family history, individuals may be less likely to undergo counseling or carrier testing themselves because they do not view themselves at increased risk when in fact they are.

One possible explanation for the difference in disclosure frequencies between those with and those without family history of an affected family member is the impact of personal experience with CF.

One possible explanation for the difference in disclosure frequencies between those with and those without family history of an affected family member is the impact of personal experience with CF.

The literature of disability studies supports the concept that personal experience with a disorder (e.g., CF) is related to more positive attitudes toward disability [Yuker, 1994], which is consistent with our study data regarding perceived severity of CF and the influence of personal experience. And yet, although carriers without exposure to CF report higher perceived severity rankings, such that one might expect that they would be more motivated to share information about reproductive risks, they were less likely to disclose. An alternate hypothesis to explain this lower disclosure rate is that nondisclosers perceive a decreased sense of the reality of risk. Many individuals who have never experienced the occurrence of an affected child in the family may perceive it to be unlikely that the event could ever happen, regardless of how they perceive severity, while individuals with personal experience may feel an increased awareness of vulnerability [Livneh, 1982].

An alternate hypothesis to explain this lower disclosure rate is that nondisclosers perceive a decreased sense of the reality of risk. Many individuals who have never experienced the occurrence of an affected child in the family may perceive it to be unlikely that the event could ever happen, regardless of how they perceive severity, while individuals with personal experience may feel an increased awareness of vulnerability.

A second possible explanation for the difference in disclosure frequencies may be that many obligate carriers did most of their telling in the context of explaining their child's diagnosis, making carrier status an inadvertent disclosure, rather than the primary one. This mode of disclosure may be useful to some relatives, but it assumes an understanding of the complexities of recessive inheritance, that relatives can determine that they are at risk, and that relatives are aware of genetic screening availability. While prenatal population screening may identify these people, it would be preferable for health care providers to encourage their patients to share this information with relatives even when they are not pregnant to give their relatives greater time to adjust to and appreciate the significance of the information and to make informed decisions about what to do with this information (e.g., whether or not to undergo carrier testing and how such information would influence reproductive plans).

Finally, very few of our respondents in either group reported that their relatives had pursued carrier testing. This may suggest that very few relatives sought testing, as has been observed in other studies (e.g., Suhr et al. [1994]), or that relatives did not tell the study subjects whether or not they had testing. In part, there was no informational utility in reporting testing decisions back to study subjects who already knew their carrier status. Relatives who underwent testing may have chosen not to reveal their status for reasons of privacy or to avoid creating a “have/have not” dichotomy within the family. Additionally, relatives who did undergo testing and learned that they were carriers may have sought social support from someone other than study participants in an effort to avoid increasing the perceived burden on study participants.

Limitations of this study include the small population size, a relatively low response rate in both groups, and differences in education and religious affiliations between groups A and B. The relatively low response rate may be due in part to the complexity and the amount of information the surveys were intended to solicit. The differences in education and religious affiliations between the groups may represent the geographic regions from which the participants were recruited. It also reflects the participation of Northwestern Memorial Hospital in an outreach program aimed at educating AJ individuals about their reproductive risks for a number of genetic conditions for which carrier screening is available. Although we hypothesized that the existence of an affected proband is the most significant factor to explain disclosure patterns, our data may not be generalizable given these confounding demographics.

Another limitation of this study is that the data regarding the subjects' disclosure to relatives and genetic testing by relatives were not independently verified in that we did not contact the relatives. It would be very informative to know what relatives understand about their own risks and their reasons for choosing to undergo or forego genetic testing. Several studies have addressed how to contact the relatives without intruding on the privacy of the proband and his or her relatives [Winter et al., 1996; Wilcke et al., 1999].

Finally, our study only assessed the dissemination of information from known carriers. We did not assess differences in the genetic counseling provided in the CF clinic versus that provided in the prenatal genetic counseling clinics, and what role these differences may have had on disclosure patterns. Nor did we question individuals in group B regarding the utility of sample letters for disclosure. Clearly, further research needs to be done to understand familial obstacles to information disclosure.

Our study documents that the frequency of and reasons for disclosing CF carrier status to relatives differ between individuals with and without an affected family member despite the fact that the reproductive risks for their relatives are the same. This has significant implications for health care professionals who counsel women and couples regarding reproductive decision-making, because accurate risk assessment is not possible for individuals who have incomplete family history information because they are uninformed or misinformed. While encouraging health care professionals to counsel all Caucasian individuals of reproductive age about CF carrier screening regardless of family history (as recommended by ACOG, ACMG, and NIH) may make this less relevant, it remains unclear how widely accepted community-based CF carrier screening will become. Additional research is needed to assess ways that health care providers can promote and encourage patients to communicate with all of their relatives in order to increase informed reproductive decision making.