Clinical genetic care in diseases predisposing to sudden cardiac death

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van Langen, I.M.

Publication date

2005

Link to publication

Citation for published version (APA):

van Langen, I. M. (2005). Clinical genetic care in diseases predisposing to sudden cardiac

death.

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Chapter ^ ^

How to survive genetic

counselling and testing in

cardiogenetics?

A survey on characteristics and expectations

of a new category of counsellees compared

with those of existing categories

IM van Langen, E Birnie, E Schuurman, JP van Tintelen, AAM Wilde, GJ Bonsel

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Abstract

Introduction: Genetic counselling and testing for preventable cardiologie disorders

predisposing to premature sudden death is a new area of interest for clinical geneticists and cardiologists. Disease-related and counsellees' characteristics are likely to result in different counselling needs, compared to existing, non-cardiologic patient groups reguiring this type of care. To guide the development of tailored care in this area, we investigated the counselling needs of several client groups, by relating their so called agenda-topics (list of desired items to discuss during the first session) to background characteristics of clients and related to their potential disease.

Patients and methods: A cross-sectional survey among a one year cohort of all eligible

counsellees attending the clinical genetics department. Multiple logistic regression analysis to compare the pattern of agenda-topics between the cardiogenetic (Cg) group and 4 non-Cg groups, and within the non-Cg group among clients with different personal and diagnostic backgrounds.

Results: 134 Cg and 332 non-Cg counsellees participated. Sociodemographic characteristics

were partly comparable to neurogenetic and oncogenetic groups. The majority of Cg-counsellees knew less than a year about the familiar disease (57% vs 29%) and most were referred by the medical specialist (55% vs. 24%) instead of taking the initiative themselves. 27% Of the Cg-group did not list any agenda-topic, compared to 16% of the non-Cg group. On average 2.6 agenda-topics/counsellee were reported (no differences between groups). Cg-counsellees reguired less information on heredity/genetics (46% vs. 74%), more on clinical characteristics and daily living (47% vs. 19%), and they had the same informational needs regarding diagnostics and treatment (39%). Cg-counsellees with a positive attitude towards additional testing more often expressed the need for agenda-topics to be discussed. All differences were statistically significant.

Conclusions: Cg-counsellees clearly differ from existing groups of counsellees in terms of

personal characteristics, propensity to list agenda-topics, and in terms of specific informational needs, overall suggesting more uncertainty, due to lack of (assimilation of) preparatory information. Clinical guidelines are urgently needed, which address the individual trade-off between quick decision-making on preventive options and adequate information exchange (dependent on specific needs) which inevitable requires more time than what is preferable from the first point of view.

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GENETIC C O U N S E L L I N G A N D T E S T I N G IN C A R D I OG E N ETI CS

Introduction

Genetic counselling and testing for cardiogenetic diseases, primary arrhythmias (e.g. the long QT and Brugada syndromes) and cardiomyopathies, is a new area of professional interest of clinical geneticist and cardiologists, facilitated by the recent discoveries of genes for these diseases [1]. Currently, counsellees attending for cardiogenetic diseases account for a quarter of the clinical genetic workload at our department. In other Dutch teaching hospitals, as elsewhere, cardiogenetic counselling is rapidly developing.

Little is known on the specific counselling needs of this patient-group, compared to those of already existing categories of counsellees in clinical genetics, attending for reproductive, predictive (e.g. Huntington's disease, breast/ovary cancer) or diagnostic reasons For these groups specific guidelines for (predictive) genetic testing have been established, usually with international coverage [2,3,4].

When compared to neurological and oncological disorders in particular, the specific features of cardiogenetic diseases are apparent. In cardiogenetics patients often do not experience continuing physical discomfort, but are aware on the risk of fatal arrhythmias, which can be prevented by the use of medication (beta blockers) or be treated by the implantation of an internal defibrillator (ICD), in combination with rules of living such as avoiding competition sports. Compliant with such prophylaxis, life expectancy is probably normal in primary electrical diseases and in many carriers of myocardial diseases. Contrary to this, in neurogenetics the course of disease is chronic and prevention is not yet possible and in oncogenetics disease course is chronic as well and prophylaxis is often associated with major invasive and mutilating surgery. Besides, in reproductive, neurogenetic and oncogenetic counselling, referral of counsellees is most often self-initiated.

Counselling needs partly consist of the need for information on the (genetic) disease concerned and related subjects. Informational needs can be translated into the concept'agenda'. Dedicated research has shown that knowledge of the clients'agenda'(questions and concerns the counsellee wants to discuss) is vital for an effective and efficient counselling process [5,6,7]. Agenda-based counselling improves perceived personal control and contributes to reduced anxiety and increased patient satisfaction [7,8,9,10],

Taking agenda-information as a primary source of information on counsellee's needs, we compared the agendas of cardiogenetic counsellees and of existing non-cardiogenetic groups of clients (who attended for neurological and oncological disorders, mental retardation/multiple congenital anomalies or miscellaneous diseases), aiming to relate differences in agendas, if observed, to characteristics of the counsellees and/or the specific diseases.

Our study addressed the following questions:

1. What are the background characteristics and the agenda topics of counsellees at the cardiogenetic outpatient clinics versus similar data from counsellees from existing groups?

2. Can we predict specific informational needs (in terms of agenda-topics) from background characteristics, in both cardiogenetic and non-cardiogenetic counsellees?

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Patients and methods

Aims and study design

The aim of the study was to investigate the agendas of counsellees, described as The questions you want to be answered'and 'Other topics you would like to discuss'.

The study was designed as a cross-sectional, multi-centre survey during one year among all eligible new counsellees, preceding the first counselling session.

Participants

All new counsellees attending the department of Clinical Genetics were asked to participate. Criteria for participation were: Being a (relative of the) index patient, fluency in the Dutch language and being older than 16 years. If a group of relatives attended the same counselling session, all relatives were eligible for participation and were requested to answer the survey individually. If a couple with only affected offspring, and no other affected relatives, attended the department, then both parents were asked to complete the questionnaire (n=6). If only one member of a couple attended (e.g. during pregnancy), while the disease was present in the spouse and/or his/her relatives, the attending counsellee was invited to participate. Excluded were patients attending the first session for multidisciplinary diagnostic purposes only (cleft lip and/or palate, Marfan syndrome and congenital hand malformations).

Cardiogenetic counsellees were invited for participation in three Dutch clinical genetic centres (Amsterdam, Utrecht and Groningen), representing approximately 85% of the total cardiogenetic population in the Netherlands at the time of the survey. The control group(s) of non-cardiogenetic counsellees all attended the Clinical Genetics Department of the AMC in Amsterdam. All participants gave written informed consent.

Setting

All new cardiogenetic counsellees at the cardiogenetics outpatient clinics were simultaneously seen by the cardiologists and the clinical geneticist in one session. If applicable and desired by the counsellee, and ECG was made and blood was taken for (diagnostic or predictive) DNA-diagnostics afterwards. If indicated, psychosocial care was offered during or (mostly) after the counselling session.

New non-cardiogenetic counsellees were counselled by a clinical geneticist or a genetic counsellor. If indicated, additional investigations were performed or initiated afterwards. Psychosocial care was offered afterwards as part of the 'predictive protocol' (neuro- and oncogenetics) or on indication, following the counselling session.

Instrument

Agendas were investigated using a questionnaire (3 parts), preceded by an explanatory letter. Counsellees were asked to fill in this questionnaire in the waiting room before attending the counselling session. The respondents were aware that their personal agendas would actually be used to guide the counselling sessions.

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G E N E T I C C O U N S E L L I N G A N D T E S T I N G IN CA R D I O G E N ETIC S

agenda topics. The counsellees could tick the option 'I have no questions or topics I would like to discuss'.

Part II of the questionnaire was aimed at collection of the following background characteristics: -The kind or name of the familial disease (if more diseases were mentioned, the one perceived as most important), -Since when the occurrence and the (possible) genetic aspects of the (most important) disease were known to the counsellee, -The number of affected relatives and their respective degrees of relationship to the counsellee, -The way the counsellee had been informed about the (possible) heritabilityofthe disease, and -Who took the initiative to make the appointment for counselling. Added were the following socio-demographic characteristics: age, sex, educational level, number of children and reproductive intentions.

In Part III of the questionnaire, only applicable to cardiogenetic counsellees, counsellees were asked if they wished additional investigations (ECG, DNA-testing) for themselves and/ or their relatives. Counsellees could tick the following options: 'Yes, I would like to undergo additional investigations', 'Today I just want information, no additional investigations', 'I do not want any investigations', and 'I leave the decision about the need for additional investigations to the medical professionals'.

The questionnaire was developed by the researchers, tested in a pilot version (n=10) and adapted accordingly. Filling in took about 15 minutes. The questionnaire is available upon request free of charges from the corresponding author.

Scoring and data management

Counsellees

The respondents were categorised into five groups, based on the (most important) disease they attended for: a cardiogenetic group (Cg, n=134), an oncogenetic group (Og, n=109), a neurogenetic group (Ng, n=31), a mental retardation and/or multiple congenital anomalies and/or dysmorphic features group (Mr/Mca, n=121) and a group with miscellaneous cardiogenetic) diseases (Mi, n=71 ).The last four groups constitute the non-cardiogenetic (non-Cg, n=332). For the description of agenda-profiles of categories of counsellees, the groups were divided into three subgroups: the Cg-group, the (predominantly predictive) Og/Ng-group (n=140) and the (predominantly reproductive) Mr/Mca/Mi Og/Ng-group (n=192).

Agenda topics

Based on the results of the pilot, 28 categories of possible agenda topics, including a category: no topics/questions were composed together with classification criteria. The classification system was validated as follows. In the first pilot two investigators independently scored the agenda topics of 40 respondents, with a third investigator reconciliating the descriptions in case of disagreement. In the second pilot another 40 questionnaires (90 agenda topics) were used to establish the revised scoring system. Seventeen agenda topics were still scored discordantly and scoring rules for these categories were refined.

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could be scored. Two or more topics that fell into the same category were counted separately. Based on very similar contents and small number of questions in these categories in all groups, reduction from 28 to 22 possible topics was performed afterwards for presentation (Table 1).

For analytical purposes these 22 topics were classified further into 3 categories, based on three main categories of questions in genetic counselling: 1. Questions related to the genetics of the disease and to genetics in general 2. Questions related to the clinical characteristics and practical consequences of the disease, 3. Questions on the possibilities and practical aspects of diagnostic or predictive (clinical and molecular) testing (Tabie 1).

Analysis

Data management and statistical analysis was conducted using Microsoft Access 2000 and SPSS for Windows 11.0, respectively.

Comparisons between groups were tested with the Chi-square or Fisher's Exact test, for categorical data and with analysis of variance for quantitative data. Multiple logistic regression analysis was used to investigate the association between the pattern of agenda topics (dependent variable) and the genetic groups (between group comparison), or among

Table 1. Agenda questions/topics and classification

Category 0: No questions

No questions/topics reported in agenda

Category I: (Knowledge or information regarding) heredity/genetics Genetic aspects of the disease (1)

Cause(s) of the disease (2)

Risk of having/getting the disease for counsellee (3) Carrier risk for counsellee or counsellee's spouse (4) Risk of having/getting the disease for children (5)

Risk of having/getting the disease for relatives (other than children) (6) Miscellaneous: genetic, unrelated to the most important disease (8) Category II: Clinical characteristics and consequences for daily living

Symptoms/severity of the disease (7) Practical consequences of the disease (11) Impact of the disease on a child's life (12)

Impact on counsellee's or parent's life if child is affected (13) Contact with other parents or support group (14) Psychosocial aspects (e.g. feelings, anxiety) (15)

Miscellaneous: non-genetic, unrelated to the most important disease (9) Category III: (Decision-making regarding) diagnostics and treatment

Diagnostic and treatment options in future offspring (20)

Options for prenatal diagnosis/prevention of disease in future offspring (18) Further explanation of diagnostic procedures on counsellee's request (16) Alternative ways of getting children (19)

Advice on choices and how to make choices (21)

Options for predictive diagnosis/prevention for counsellee or relatives (17) Treatment options for counsellee or relatives (10)

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G E N E T I C C O U N S E L L I N G A N D T E S T I N G IN C ARD I O G E N ET ICS

counsellees of the same group (within group comparison). For the within cardiogenetics subgroup analysis the following covariables were added: site of clinical genetic department, type of cardiogeneticdisease(LQTS/HCM/other/unknown), preference for immediate additional testing (yes/no/medical specialist should decide) and attending for predictive reasons (yes/no). Variables were not reported if no significant effect was found in any of the five analyses. The outcome was expressed as (adjusted) Odds-ratio's (with 95% confidence-intervals). A two-sided p-value <0.05 was considered statistically significant.

Results

Characteristics of counsellees

501 counsellees were invited for participation. Five cardiogenetic counsellees and 21 counsellees from other groups declined participation (9.7%). Of 475 questionnaires returned, nine were excluded from analysis due to missing data on the (genetic) disease. The questionnaires of the remaining 466 counsellees were categorised into five groups (see Methods): Cg:n=134, Og:n=109, N:ng=31, Mr/Mca:n=121, Mi:n=71. For most analytic purposes the last four groups were combined into the non-cardiogenetics group (non-Cg, n=332). Most counsellees in the Cg group attended for the long QT syndrome (n=73, 55%) and hypertrophic cardiomyopathy (n=25,19%) respectively.

Sociodemographic characteristics (Table 2)

Compared to the non-Cg group, Cg counsellees group more often were men (54% vs 23%), >40 years of age (52% vs. 26%), more often had children (68% vs 47%) and less often desired future children (19% vs 51%). All differences were statistically significant. The Cg group resembled most the Og and, to a lesser extent, the Ng groups.

Background characteristics (Table 3)

The majority of Cg counsellees (56%) was aware less than one year of their potential risk status, compared to 29% in the non-Cg group. Cg counsellees more often received information about the genetic disease from relatives (either orally or by a family letter supplied by the medical team) compared to the non-Cg group. In the Cg group, a medical specialist (cardiologist) (55%) or a family member (18%) usually initiated referral while in the non-Cg group often the counsellee (36%) or GP (19%) took the initiative (overall: p<.001). Cg counsellees were more often self affected (35% vs. 18%). The Cg group usually (74%) attended for predictive (clinical and/or molecular) diagnostic testing for themselves or their child(ren).

Agendas (Figure 1)

Eighty-eight of 466 counsellees (18.9%) did not report any agenda topics prior to the first consultation (Cg 26.9%, Og 20.2%, Ng 22.6%, Mr/Mca 10.7% and Mi 14.1%, p=.015). This proportion was significantly higher in the Cg group (n=134) compared to the non-Cg-group (n=332) (26.9% vs. 15.7%, p<.01).

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Figure 1. Relative frequencies of agenda topics* prior to the first consultation by five groups ofcounsellees

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G E N E T I C C O U N S E L L I N G A N D T E S T I N G IN C ARD I OG E N ETI CS

The remaining 378 counsellees reported 966 questions (mean: 2.6 questions per responding counsellee, range: 1 -5). The mean number of topics per counsellee did not significantly differ between groups.

Figure 1 shows the frequency of the reported agenda topics in the Cg and control groups, based on the nine most prevalent topics in the Cg group . Among the counsellees reporting at least one agenda-topic, the proportions of reported top-9 topics differed significantly between the five groups as well as between the Cg-group and non-Cg group. The Cg-group reported significantly more questions on: Symptoms and severity of the disease (24% vs. 7%);Treatment options (8% vs. 2%); and Practical consequences of the disease (5% vs. 0.3%). The Cg-group reported no questions on: Options for prenatal diagnosis/prevention in future offspring (0% vs. 6%). No counsellee had questions on: The impact on parent's/counsellee's life if their child is affected (item 13, Table 1) or: Contact with other parents/support groups (item 14). Topics on Psychosocial aspects (item 15) were not reported by the Cg-group and only infrequently by non-Cg counsellees (0.5%). Advice on how to make choices (item 21) was also requested infrequently (2% vs. 3%).

Cardiologie and/or genetic testing was offered to the Cg-group at the same consultation. Of the Cg counsellees, 37% preferred decision making and testing the same day while 57% left this choice to the medical specialist(s), The remaining 6% preferred to receive information first and to decide and test later. Data on the other groups were by design unknown.

Description of profiles of agenda topics (Figure 2)

Figure 2 shows a Venn-diagram representation of the informational needs of three categories of counsellees (see Methods), expressed in Category I (=Knowledge or information regarding heredity/genetics), II (=Clinical characteristics and consequences for daily living) and III (=Decision-making regarding diagnostics and treatment, also see Table 1). Cg counsellees

Figure 2. Distribution of agenda topics according to three categories of topics (I: Know-ledge/information regarding heredity/genetics; II: Clinical characteristics /consequences for daily living; III: Decision making regarding diagnostics and treatment) and three groups of counsellees (Cg: cardiogenetics; Og/Ng: oncogenetics/neurogenetics; and MR /Mca/Mi*)

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G E N E T I C C O U N S E L L I N G A N D T E S T I N G IN C A RDI OG EN ETI C S

reported relatively few Category I topics compared to Og/Ng and Mr/Mca/Mi counsellees (61/111, 62% vs. 97/111, 87%, vs. 149/169, 88%) but relatively many Category II topics (63/111, 63% vs. 19/111, 17%, vs. 43/169, 25%) and a similar amount of Category III topics (53/111, 54% vs. 57/111, 51%, vs. 72/169,43%). The majority of counsellees who reported at least one topic from Category I also reported at least one additional topic from Category ll/lll (58%), a proportion being higher in the Cg group than in the Og/Ng and MR/Mca/Mi groups (80% vs. 53% vs. 53%).

Multiple regressions

Associations between groups of counsellees (Table 4)

Table 4 displays the significant results from the five multiple logistic regression analyses. Higher educated counsellees and counsellees who had received information by other means than by a family letter were significantly more likely to report (at least one) agenda topic(s). Cardiogenetic counsellees and younger counsellees in general had broader informational needs. Counsellees who received information by other means than by letter increased the probability of reporting topics from category I. Cardiogenetic counsellees compared to the counsellees of other groups had a lower probability of reporting category I topics as such and a higher probability of reporting category II and III topics and, when mentioning category I topics, had also a higher probability of reporting category II or III topics at the same time.

Associations within the group of cardiogenetic counsellees

There were two significant predictors associated with having at least one agenda-topic within the cardiogenetic group. For all diagnostic cardiogenetic categories this was/Attitudes towards additional diagnostic investigations', with counsellees having positive attitudes also having a greater chance of reporting informational needs. The other one was 'Kind of disease', with counsellees from Hypertrophic Cardiomyopathy families in particular having a greater chance of reporting informational needs. The informational needs of Cg-counsellees did not depend on their centre or on their sociodemographic backgrounds.

Discussion

In our one year cohort of clinical genetic counsellees we demonstrated significantly different informational needs between new and already existing clinical genetics groups (cardiogenetic and non-cardiogenetic: neurogenetic, oncogenetic, mental retardation/multiple congenital anomalies, miscellaneous) and even within the focus group of cardiogenetic counsellees. The cardiogenetic group resembled the onco- and neurogenetic groups most regarding sociodemographic characteristics. In general, cardiogenetic counsellees were informed about their genetic risks more recently than the non-cardiogenetic groups, and typically referral was initiated by a medical specialist more often than by the counsellees themselves, which is different from other groups.

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when they surpassed the threshold for listing their agendas, had in particular broad needs to discuss genetic as well as clinical, practical, diagnostic and therapeutic aspects of the diseases concerned. The non-cardiogenetic groups more often expressed questions on genetics and on diagnostic options only. Disturbingly, 27% of cardiogenetic counsellees showed no informational needs at all this way, while from a clinical point of view it is hard to imagine that laymen by nature are fully informed on cardiogenetic patient-relevant evidence. More probably these counsellees were still overwhelmed by the recently obtained information on their own and their children's risks. This may be even truer for the less educated counsellees and those who were initially informed by a family letter only. Very few counsellees in general, and none from the cardiogenetic group, spontaneously suggested that they wanted to discuss feelings of uncertainty and worry at first consultation or would like to get in touch with support groups. The cardiogenetic counsellees were also not interested in discussing prenatal diagnostic options. Of course, these needs may very well emerge during or after the first consultation.

Literature

Relevant literature for comparison consists of four agenda-papers in oncogenetics (breast/ ovary cancer) and one in general clinical genetic practice [6,11,12,13,14]. In line with the data from our oncogenetics population, these women were initially mainly interested in their own risks in getting cancer (again) and not primarily in the explanation of clinical, preventive and therapeutic options. Hallowel et al report that before attending the first session 28% of counsellees had no questions to ask and viewed their roles as passive. Afterwards they felt that they not obtained optimum benefit because of inadequate preparation. Remarkably, counsellees in a general clinical genetics department considered the discussion of'treatment options' more often important than their genetic counsellors, possibly suggesting that counsellors are less alert in handling these kind of questions than other medical specialists (like cardiologists) and primary care givers.

Limitations

We are well aware of some limitations of our study in this developing area. Genetic counselling and testing is a cyclic consultation process of which we only cross-sectionally investigated the initial informational needs of our counsellees. Also the way in which we gathered the agenda-items, by means of a written questionnaire with open-ended questions, shortly before the first consultation, may have influenced the results. Counsellees were aware on the other hand that their list of agenda-items would actually be used during the consultation, which may have increased validity. The expression of informational needs may have been biased by the fact that cardiogenetic counsellees knew that a cardiologists would be present during the first consultation, possibly inducing different expectations. Offering open-ended questions on informational needs (agendas) requires reflective, educated and active counsellees. The cardiogenetic group seems disadvantaged in these respects, unknown is by which primary mechanism. Comparison of results from cardiogenetic clients and non-cardiogenetic groups may have been hampered by a centre-effect, although we could not demonstrate such an effect within the cardiogenetic group however.

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G E N E T I C C O U N S E L L I N G A N D T E S T I N G IN CA R D I OG E N ETICS

Possible consequences for cardiogenetic counselling and testing

Current clinical guidelines concentrate only on the medical management of cardiogenetic patients [1,15]. Because genetic testing in cardiogenetics is often predictive, the use of guidelines designed for predictive counselling in neurogenetics and oncogenetics has been advocated for this group [2,4,16,17].These guidelines aim to support the patient's autonomy and the self-selection of those applicants with sufficient ego-strength to handle possible negative consequences of the genetic test. The guidelines for predictive testing prescribe waiting-periods between the first sessions and the drawing of blood. Following the guidelines, the psychosocial consequences of predictive counselling and testing are mild in these groups [18,19,20,21]. However, predictive testing in the long QT syndrome is associated with considerable psychological distress [22]. Compliance with prophylactic measures can expected to be less, when distress is severe [23]. Adequate support-models have to be developed.

Many of the cardiogenetic counsellees will have trouble with the expected active participation during the first visit, at least in our study. Many choices in preventable diseases like most cardiogenetic disorders seem obvious on the one hand, however, the predictive counselling and testing protocol in cardiogenetics explicitly require an informed, balanced choice. The immediate threat of sudden death in some carriers of cardiogenetic diseases is at conflict with the stated time for reflection however. This trade-off is clear but more research is required to define optimal terms.

Figure 3. Proposed guidelines for predictive testing in cardiogenetics (adapted from the

Huntington guidelines and revised from ref 2)

1. Genetic counselling (including the drawing of an extended pedigree), extension of cardiologie evaluation (if necessary) and DNA testing of the index patient in a multidisciplinary outpatient cardiogenetics clinic

2. If a mutation is detected: education of the index patient and initiation of cascade screening 3. Information of first and second degree relatives by the index patient (if necessary by the medical

specialists), using an information letter written by the medical team and/or web based (interactive) supply of information.

4. Genetic counselling of relatives prior to testing, during a family meeting and/or individually 5. Clinical and/or DNA testing of relatives at first consultation if necessary regarding the actual risk of

sudden death

6. Clinical and/or DNA testing of relatives at second appointment if considered safe by the cardiologist 7. Psychosocial care (psychologist, social worker) actively offered at first consultation and mandatory for all

families in whom minors are tested

8. Results given personally, by telephone or by letter, dependent on the preference of the individual 9. Actively offered follow-up appointments (including psychosocial care) for mutation carriers, especially

for those having children

10. Cardiologie testing and follow-up in mutation carriers, or referral for testing and follow-up to a cardiologist familiar with the disease in the neighbourhood of the residence of the mutation carrier

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Which implications can be envisaged for predictive testing (cardiological as well as molecular) in cardiogenetics (Figure 3)? Firstly, more factual knowledge on the disease running in a certain family could be supplied to the counsellee before the first visit. During the first consultation additional information can be given, based on the personal agendas of the counsellees. Based on clinical knowledge of the disease concerned, the personal and family history of the counsellee and (in selected cases) on the results of additional cardiologie investigations (electrocardiogram), the cardiologist can make a prediction of immediate risk . If this risk is expected to be small, planning a second visit might be appropriate. In the meanwhile, and even more when children are eligible to be tested, consultation(s) of a social worker or psychologist can be planned. In specific clinical (high risk) cases however, genetic testing should be performed at first visit. In carriers, the attending cardiologist will have to deal with emerging informational and psychosocial needs. Of course, follow up visits with the clinical geneticist may be appropriate, especially when questions on reproduction occur.

Conclusions

This survey shows that the cardiogenetics population is unique for the clinical genetic practice. The informational needs of this population cover the fields of cardiology as well as (clinical) genetics. Multidisciplinary counselling is therefore delivered. Counsellees as well as counsellors have to trade off the feelings of urge induced by the acute risks of the cardiogenetic diseases and the time to deliberate required for a proper counselling process. Guidelines for (predictive) testing in cardiogenetics should therefore be tailored to the individual situation. We need future process- and satisfaction studies to evaluate if these protocols meet the expectations.

Acknowledgements

We would like to thank all counsellees who responded to our survey. We thank Phia Kuijten-Smid, research assistant, for practical help in preparing and handling of the survey and dr.E.M.A. Smets, psychologist for assistance in the validation of the scoring of agenda items. We are grateful to Irene Stolte-Dijkstra for her help in referral of cardiogenetic patients in Groningen.

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References

1. Priori SG, Barhanin J, Hauer RN, Haverkamp W, Jongsma HJ, Kleber AG et al. Genetic and molecular basis of cardiac arrhythmias; impact on clinical management. Study group on molecular basis of arrhythmias of the working group on arrhythmias of the European society of cardiology. Eur Heart J 1999; 20:174-195. 2. van Langen IM, Hofman N.Tan HL, Wilde AA. Family and population strategies for screening and counselling

of inherited cardiac arrhythmias. Ann Med. 2004;36 Suppl 1:116-24.

3. International Huntington Association and the World Federation of Neurology Research Group on Huntington's Chorea. Guidelines for the molecular genetics predictive test in Huntington's disease. J Med Genet 1994;31:555-9.

4. Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC, Manley S, Culver JO, Acton R, Larsen-Haidie J, Correia LA, Bennett R, Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C, Farrell C, Callif-Daley F, Vockley CW; National Society of Genetic Counselors. Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 2004;13:83-114. 5. Sorenson J.R., Swazey J.P., and Scotch N.A. Effective genetic counseling: discussing client questions and

concerns. Birth Defects Orig.Artic.Ser 1981;17:1-192.

6. Van Asperen CJ, Van Dijk S, Zoeteweij MW,Timmermans DR, De Bock GH, Meijers-Heijboer EJ, Niermeijer MF, Breuning MH, Kievit J, Otten W. What do women really want to know? Motives for attending familial breast cancer clinics. J Med Genet. 2002 Jun;39:410-4.

7. Berkenstadt M, Shiloh S, Barkai G, Katznelson MB, Goldman B. Perceived personal control (PPC): a new concept in measuring outcome of genetic counseling. Am J Med Genet. 1999;82:53-9.

8. Marvel MK, Epstein RM, Flowers K, Beekman HB. Soliciting the patient's agenda: have we improved? JAMA 1999;281:283-7.

9. Michie S, Marteau TM, Bobrow M. Genetic counselling: the psychological impact of meeting patients' expectations. J Med Genet 1997;34:237-41.

10. Wertz DC, Sorenson JR, Heeren TC, Communication in Health Professional-Lay

Encounters: How Often Does Each Party Know What the Other Wants to Discuss? Information and Behavior, Trans-Action Books, New Brunswick, NJ 1988;329-342.

11. Brain K, Gray J, Norman P, Parsons E, Clarke A, Rogers C, Mansel R, Harper P. Why do women attend familial breast cancer clinics? J Med Genet. 2000;37:197-202.

12. Julian-Reynier C, Eisinger F, Chabal F, Aurran Y, Bignon YJ, Nogues C, Machelard M, Maugard C, Vennin P, Sobol H. Cancer genetic clinics: why do women who already have cancer attend? Eur J Cancer 1998;34:1549-53. 13. Hallowell N, Murton F, Statham H, Green JM, Richards MP. Women's need for information before attending

genetic counselling for familial breast or ovarian cancer: a questionnaire, interview, and observational study. BMJ 1997;314:281-3.

14. Shankar A, Chapman R Goodship J. Genetic counselling: do we recognise and meet the consultands'agenda? J Med Genet 1999;36:580-2.

15. Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ, Wigle ED; Task Force on Clinical Expert Consensus Documents. American College of Cardiology; Committee for Practice Guidelines. European Society of Cardiology. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687-713.

16. Charron R Heron D, Gargiulo M, Richard R Dubourg O, Desnos M, Bouhour JB, Feingold J, Carrier L, Hainque B, Schwartz K, Komajda M. Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience. J Med Genet 2002;39:741-6.

17. Charron P. [Genetic counseling in cardiology]. Arch Mai CoeurVaiss 2003;96:1131-4.

18. Duisterhof M, Trijsburg RW, Niermeijer MF, Roos RAC, Tibben A. Psychological studies on Huntington's disease: making up the balance. J Med Genet 2001;38:852-61.

19. Broadstock M, Michie S, Marteau T. Psychological consequences of predictive genetic testing: a systematic review. Eur J Hum Genet. 2000,8:731-8.

20. Almqvist EW, Bloch M, Brinkman R, Craufurd D, Hayden MR. Worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. Am J Hum Genet.. 1999;64:1293-304.

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testing and counselling in breast cancer: a systematic review. Med J Aust 2003;! 78:77-81.

22. Hendriks K5, Grosfeld FJ, Wilde AA, van den Bout J, van Langen IM, van Tintelen JR ten Kroode HF. High distress in parents whose children undergo predictive testing for long QT syndrome. Community Genet 2005;8:103-13.

23. Lerman C, Daly M, Sands C, Balshem A, Lustbader E, Heggan T, GJoldstein L, James J, Engstrom P. Mammography adherence and psychological distress among women at risk for breast cancer. J Natl Cancer Inst 1993;85:1074-80