Parental Knowledge and Attitudes Toward Hypertrophic Cardiomyopathy Genetic Testing
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- Fitzgerald-Butt, S.M., Byrne, L., Gerhardt, C.A. et al. Pediatr Cardiol (2010) 31: 195. doi:10.1007/s00246-009-9583-2
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Hypertrophic cardiomyopathy (HCM) is a common autosomal dominant condition with an increased risk of sudden cardiac death. Although clinical genetic testing can be used for confirmation of a clinical diagnosis as well as a predictive test, based on our clinical experience it is underutilized. Therefore, we developed and administered a questionnaire to assess potential determinants of parental interest in this testing. Of the 30 adult caregivers who participated, 80% had heard of genetic testing, whereas only 30% knew about genetic testing specifically for HCM. Once informed of the availability, 62% said they would consider testing in the future and 28% would consider it in the next year. Participants’ younger age, higher education level, knowledge of carrier testing, and positive view of genetic testing were significantly associated with the participant considering HCM genetic testing for their child (p ≤ 0.05). Based on a logistic regression model, age, education level, and knowing that HCM is an inherited disease were the best predictors of who would consider genetic testing. This study provides healthcare providers with a framework to understand caregivers’ knowledge and views of genetic testing, which can be used to improve clinical care for pediatric HCM patients.
KeywordsHypertrophic cardiomyopathyGenetic screeningGenetic counselingPediatricHealth knowledge attitudes practice
Left ventricular hypertrophy is a clinical sign associated with a number of disease states in both pediatric and adult patients. When no other cause can be determined, a patient is said to have idiopathic hypertrophic cardiomyopathy (HCM). Idiopathic HCM is known to be a common genetic disease that has been estimated to affect 1/500 people in the general population . It is a frightening diagnosis for most patients due to the risk of sudden cardiac death. For relatives this diagnosis should also be alarming because it is inherited in an autosomal dominant manner, thus putting all first-degree relatives (siblings, parents and children) at a 50% chance of also carrying the disease causing mutation. Because the phenotype (e.g., asymptomatic, syncope, heart failure) and the age at presentation (infancy to old age) are both highly variable  all relatives are at risk regardless of age or lack of symptoms. Therefore, regular clinical screening consisting of a physical examination by a cardiologist, electrocardiogram, and echocardiography is recommended . Because this screening only captures the current clinical state, it must be completed regularly starting in childhood and continuing throughout adulthood. This may impose a financial and emotional strain on the individual and their family when this screening is realistically necessary for only 50% of those screened. Genetic testing is the only method currently available to determine specifically which relatives have a disease-causing mutation and therefore require clinical screening.
HCM genetic testing has been clinically available since 2005, and testing panels that are currently available include 3 to 17 genes. Nine of these genes (MYH7, MYBPC3, TNNT2, TNNI3, TNNC1, TPM1, MYL2, MYL3, and ACTC) code for cardiac sarcomere proteins, whereas the rest are metabolic disorders that can cause left ventricular hypertrophy. Mutations are identified in approximately 40% of unselected individuals with HCM [26, 29], and in >60% of those with a family history of HCM or sudden cardiac death . Most mutations in the cardiac sarcomere genes are inherited  and private  with few mutations are found in multiple families. Although some genotypes are associated with an increased risk of sudden death, genotype is not predictive of phenotype or age of onset in most cases . A succinct review of clinical care  and an extensive review of molecular pathogenesis  are available.
With the exception of an ethical debate article that included a parental narrative on their decision to test their infant for HCM , we were unable to identify literature addressing whether patients or parents are aware of HCM genetic testing or the determinants of interest in HCM genetic testing. From a clinical perspective, a recent survey of Dutch cardiologists showed that <60% informed all of their HCM patients of the genetic nature of HCM, and <40% informed all HCM patients of the need for familial screening . Likewise, in an unselected ovarian cancer patient population, 55% were not aware of genetic testing for hereditary breast and ovarian cancer . These studies begin to establish that there is a general lack of knowledge of the genetic basis and availability of genetic testing among patients with multifactorial diseases.
Due to this lack of knowledge and our own clinical observation that patients do not seem to be informed of the availability of genetic testing for HCM, we undertook this study to determine (1) whether adult caregivers of pediatric HCM patients are aware that HCM is inherited and that genetic testing is available and (2) their attitudes toward genetic testing and determinants of pursuing genetic testing.
This study was approved by the Institutional Review Board at Nationwide Children’s Hospital, a pediatric tertiary care hospital. To identify participants, the Division of Pediatric Cardiology echocardiography database was queried for patients with cardiomyopathy (per ICD-9 codes 425.1 or 425.4) evaluated between June 2, 2004, and June 20, 2007. Their medical records were then reviewed to identify those without a known cause of HCM and therefore a diagnosis of primary idiopathic HCM. The parents of these patients were sent a letter introducing the research study and informing them that they could decline to be contacted. Multiple attempts were made to contact all parents, and all questionnaires were completed between August 13 and September 20, 2007.
The telephone questionnaire consisted of demographic information on the adult caregiver participant (“participant/s” hereafter) and the patient (7 questions), HCM diagnosis (3 questions), cause of HCM (6 questions, adapted from McLaren et al. ), sources of information about HCM (7 questions), family history of HCM (2 questions), attitudes toward general genetic testing (10 questions, 8 of which were developed by McLaren et al. ), familiarity with genetic testing (7 questions), and whether they had or would consider genetic testing for HCM (3 questions). Most questions were closed-ended and had yes/no or a 4-point Likert scale (0 = strongly disagree to 3 = strongly agree) answers. Two questions were open ended and were scored as correct or incorrect. Participants were asked twice if they or their child had already undergone HCM genetic testing, and we found 100% correlation between answers. After the study, additional information on genetic testing for HCM was sent to all participants who requested it.
The questionnaire data were entered into a relational database and exported to Stata Statistical Software (release 10; StataCorp LP, College Station, TX) for analysis. In addition to descriptive statistical analysis, participants’ responses were analyzed for a relationship with whether they would consider genetic testing. Due to the small sample size, during statistical analysis participants who had already undergone HCM genetic testing were included along with those who would consider genetic testing. Two-sided Student t tests were used for continuous variables, Fisher’s exact test for categoric variables and summed rank test for ranked categories with p ≤ 0.05 were considered statistically significant. Because this was exploratory research with a small sample size, responses with p ≤ 0.10 were tested stepwise (forward and backward) in a logistic regression model. Variables were assessed for colinearity by the magnitude of the SE and calculation of the variance inflation factor during linear regression analysis. The final model was tested with Pearson’s goodness-of-fit test.
Of the 322 patients with cardiomyopathy, 41 had primary idiopathic HCM. Letters were sent to the parents of these patients, and none of them declined to be contacted. Four potential participants were ineligible (three did not have a working phone number, and one patient did not have a living adult caregiver). Despite at least four attempts, we were unable to contact three potential participants. Of the 34 families contacted, 4 declined participation. Therefore, participants included 73% of families who were notified of the study and 88% of those contacted.
Demographics of study participants (n = 30)
Relationship to child
High school diploma or less
Some college or more
HCM Diagnosis, Cause, and Family History
The majority of participants (80%) correctly named their child’s heart condition using a medical (HCM, HOCM, IHSS, cardiomyopathy) or nonmedical (“heart thickening”) term. Patients were diagnosed with HCM at an average age of 6.6 years (range birth to 15; SD 5.9) and it had been, on average, 8.1 years (range 0 to 21; SD 5.0) after diagnosis. Although heart murmur was the symptom that led the majority (70%) of children to be diagnosed with HCM, 13% reported that their family history of HCM was the precipitating factor. Almost half of the participants (43%) had a family history of HCM, and most participants (67%) thought that other relatives might develop HCM.
Sources of Information
Cardiologists were identified as helpful sources of information about HCM by most participants (96%), whereas 53% identified their pediatrician and the Internet as helpful sources. Other healthcare professionals, books or magazines, friends or family members, and other sources were identified as helpful by a minority of participants (24, 33, 24, and 6%, respectively).
Nearly all of the participants (87%) stated that they had heard of genetic testing, and 67% of all participants (80% of those who had heard of genetic testing) were able to correctly describe genetic testing. Those who were unable to accurately describe genetic testing were told the following: “Genetic tests are blood tests that examine genes, which are responsible for physical traits like eye color. Changes in genes can lead to health conditions.”
Family history and familiarity with genetic testing
Relatives will develop HCMa
Relatives with HCM
Heard of genetic testing
Heard of genetic testing for:
Sickle cell disease
Had of genetic testing for:
Sickle cell disease
HCM genetic testing:
HCM Genetic Testing
Participants were also asked if they had heard of and if they or their child had undergone HCM genetic testing. Nine participants (30%) had heard of HCM genetic testing and of these, four participants stated that they or their child had already undergone HCM genetic testing. Once made aware of the availability of HCM genetic testing, 62% said they would consider HCM genetic testing for themselves or their child and 28% would do so in the next year. At the completion of the questionnaire, 83% of participants responded that they would like an information sheet on HCM genetic testing to be sent to them.
Determinants of Consideration of Genetic Testing
Statistical analysis indicated that participants’ age (p = 0.02), education level (p = 0.05), agreement that genetic testing can help one prepare for the future (p = 0.04), agreement that genetic testing can lead to better treatments for disease (p = 0.03), and knowledge of carrier testing (p = 0.03) were significantly related (p ≤ 0.05) to whether the participant would consider genetic testing for HCM. Participants who would consider HCM genetic testing were younger (mean 42.6 and SD 7.2 vs. mean 48.4 and SD 6.6) and had more years of education (mean 14.9 and SD 2.9 vs. mean 13.1 and SD 2.2) than those who would not consider testing. Because only nine participants answered that they would consider having HCM genetic testing in the next year, these data were not analyzed due to a lack of statistical power.
Logistic Regression Model
A multivariate model was constructed to examine which determinants accounted for unique variance in whether participants would consider HCM genetic testing. To build the best model, variables that differentiated these two groups with p ≤ 0.10 were considered as potential predictors. In addition to those with p ≤ 0.05 (as listed previously), this analysis included the following factors: knowing that HCM is inherited (p = 0.06) and having heard of HCM genetic testing (p = 0.10). The best logistic regression model was achieved when age, education level, and knowing that HCM was inherited were included (p = 0.008), with goodness-of-fit p = 0.58 and no obvious collinearity.
Although the first HCM gene was found in 1990 [7, 24] and clinical testing has been available since 2005, there is a complete lack of literature on patient or parent interest in and attitudes toward genetic testing for HCM. The psychosocial literature in inherited cardiac conditions has focused on the quality of life of affected individuals and carriers [2, 17, 23], uptake of clinical screening [5, 25], genetic counseling and testing among relatives  and the benefits of specialty clinics [5, 10, 28]. These are important areas to explore for children and adults who have already undergone genetic testing. Although genetic testing has been recommended for individuals with HCM since 2006 , it has not yet been incorporated into routine practice across the United States. Therefore, many children with HCM have yet to receive genetic testing and/or genetic counseling. To our knowledge there is a lack of published literature addressing parents’ understanding of the inherited nature of their child’s heart condition and awareness of and attitudes toward genetic testing. Therefore, this study examined a new and important area among adult caregivers unselected for genetic counseling, genetic testing, or a family history of HCM.
In our survey of adult caregivers of children diagnosed with idiopathic HCM, we found that although more than three-fourths of the participants were aware that HCM is inherited, less than one-third were aware that genetic testing is available. After being informed of the availability of HCM genetic testing, 62% of participants said they would consider having this test. Although not the purpose of this study, a number of participants learned of the availability of genetic testing for HCM, which may benefit their families. In this population, parental age, education, positive attitude toward genetic testing, and knowledge of carrier testing were each significantly associated with who would consider genetic testing. Parental age, education level, and awareness that HCM is inherited were the best predictors of interest in HCM genetic testing. Due to confidentiality we were not able to determine whether the interested participants did indeed pursue genetic counseling or genetic testing after completing the questionnaire.
In many studies, delineation of risk to children is cited as one of the major reasons individuals are interested in and/or pursue genetic testing. Unfortunately, little research has been focused on parents’ motivation to pursue genetic testing for their children when their child is affected. Parents have been found to have a positive attitude and a general interest in genetic testing in case [18, 21] and cohort studies [3, 19, 22]. Their positive view of genetic testing may be related to the changes in medical management or lifestyle during childhood that can detect, prevent, or treat these diseases (e.g., familial adenomatous polyposis, deafness, childhood cancer, obesity).
A child with HCM may benefit from genetic testing both psychologically and medically. Because pediatric HCM can be caused by inborn errors of metabolism, malformation syndromes, and neuromuscular diseases, we have seen in our clinical practice the benefit provided to parents by knowing that their child is not at risk for multisystem disease and/or having an explanation for their child’s HCM. In addition, genetic testing has been shown to have no impact on the health-related quality of life of children who are carriers of inherited cardiovascular conditions  and adults who have HCM . Furthermore, adult carriers of HCM had a better quality of life and less distress than the general population . In addition, there are genotype–phenotype correlations for patients with troponin T (TNNT2) and certain beta-myosin heavy-chain (MYH7) mutations. Although only 3–5% of HCM patients have TNNT2 mutations, these patients are at increased risk for sudden death with a lesser amount of left ventricular hypertrophy at younger ages. Although mutations in MYH7 are associated with variable but usually moderate to severe disease, individuals with the Arg403Gly and Arg453Cys mutations have a highly penetrant disease with severe left ventricular hypertrophy (LVH) and higher risk for sudden death. Therefore, although a minority of patients will have these malignant genotypes, due to the changes that would be made in their medical management to avoid sudden death, identification of these individuals through genetic testing is important.
When a child with HCM undergoes genetics testing, not only do the results possibly affect their own diagnosis and medical management, they can also lead to screening, genetic testing, and identification of asymptomatic mutation carriers amongst siblings, parents, and other relatives. Studies from The Netherlands have shown that relatives are interested in determining their own risk for HCM. When relatives were informed of the recent diagnosis of HCM in their family by way of a letter, 42% sought consultation with a cardiologist and/or geneticist . Likewise, in response to a letter about the identification of a HCM causing mutation in their family, 39% of relatives received genetic counseling, with 99% of those relatives deciding to pursue genetic testing . Another study found that when asymptomatic relatives undergo genetic testing and are found to have an HCM causing mutation, three quarters of them receive cardiac care . These individuals see their cardiologist, on average, every 16 months and in general receive a sense of reassurance from these visits. Therefore, although a clinical trial has not yet proven that genetic testing in relatives saves lives, it is clear that relatives are interested in determining their own risk of disease and obtaining appropriate medical care. Furthermore, the Heart Failure Society of America, in its recently released guidelines, has recommended that genetic testing be considered for the “most clearly affected person in a family to facilitate family screening and management” . As genetic testing for HCM continues to be incorporated into more professional guidelines, discussing genetic testing with HCM patients and their families will become a routine practice in the United States.
Although genetic testing can be beneficial to pediatric patients and their families, those benefits come at a cost and with some potential risks. First, testing a panel of genes known to cause HCM currently costs a few thousand dollars in the United States. This cost is commonly covered, at least partially, by health insurance, but coverage varies vastly. If a causative mutation is identified, a stepwise method of testing relatives is recommended in which first-degree relatives of the affected individual are tested for that specific mutation at a cost of a few hundred dollars. Then if additional relatives test positive, their first-degree relatives are then tested, and so on. Approximately 40% of individuals with HCM who undergo genetic testing will have a normal result . In this case, the affected individual still has a diagnosis of HCM, but because genetic testing of relatives is not possible, all relatives will need to continue regular clinical screening. Rarely, the result of a HCM genetic test is a variant of unknown significance. Because a genetic mutation has been identified but is not known to be a benign variant or a disease-causing mutation, testing additional affected family members for this genetic mutation may help clarify whether the mutation is causative. Last, patients should be informed of the health insurance and employment protections granted under the Genetic Information Nondiscrimination Act because genetic discrimination is a concern for many. Although genetic testing may not always provide a clear explanation for families, the potential benefits outweigh the risks for most families.
As the results of this study begin to build a foundation of understanding, it is important to consider the results in the context of several limitations. First, our sample included only those parents whose children had an echocardiographic examination within the study period at a single children’s hospital, who had a valid address and phone number, and who were able to be contacted by phone. Therefore, participants may not be representative of the larger population of caregivers of children with HCM. Consequently, this study must be expanded to multiple sites because the attitudes of caregivers and practice of health care professionals are likely to differ by hospital and by geographic location. A larger, more diverse sample may also improve the power to distinguish differences based on race, caregivers’ relationship with the child, and familiarity with genetic testing. In addition, a larger sample size would allow us to investigate the effect of additional characteristics of participants that were not collected as part of this study. As the role of adult caregivers in gathering medical information gathering and making medical decisions changes as the child ages, a larger sample would allow us to further delineate the effect of the child’s age, age at diagnosis, and years since diagnosis. Likewise, the potential influence of whether the adult caregiver had been screened and/or diagnosed with HCM themselves is important to explore. Last, a larger sample size would make it possible to ask participants about diagnostic and predictive HCM genetic testing separately and to determine if their attitudes differed based on the purpose of the testing. Although this study has limitations, it makes an important initial contribution regarding adult caregiver knowledge of HCM genetic testing availability as well as their attitudes and determinants to pursing genetic testing.
Despite these limitations, this study indicates that further research in this area is feasible. We successfully recruited participants for this study, with almost 90% of individuals who were contacted completing the study. In addition, most participants answered all of the questions. Last, a number of the questions used in this study were designed for and used in a large population-based study. Thus, although these questions have not been validated, they have been tested in an ethnically diverse population of >50,000 individuals. These factors led to high-quality data and significant statistical findings despite our small sample size.
Because research in this area is feasible, we would like to expand not only the number and diversity of our participants but also the basic questionnaire. In a future study, we would include additional questions to assess if participants had been screened/diagnosed with HCM themselves, which sources were helpful for information on the genetics of HCM, and their attitude toward HCM diagnostic and predictive genetic testing. With this more detailed knowledge of parents’ knowledge and attitudes, we could begin to address specific informational gaps to ensure that all patients and families are able to access the benefits of genetic testing.
The authors acknowledge Elizabeth Varga for her critical review of this manuscript. Funding for this project was received from The Research Institute at Nationwide Children’s Hospital.