Praktisk håndtering af den genetiske kardiologi

1. Praktisk håndtering af den genetiske kardiologi The Heart Centre Henning Bundgaard REAH, The Heart Centre Diagnostic Centre Juliane Marie Centre

2. Danish national recommendations A working group under Danish Society of Cardiology with significant contributions from • Cardiologists representing several sub-specialities • Clinical geneticist • Paediatricians • National Board of Health • Specialists in legal aspects of medicine • Ethicist

3. The working group and other contributors Henrik Kjærulf Jensen, Henning Mølgaard, Lars Køber, Jesper Hastrup Svendsen, Peter Clemmensen, Jens Erik Nielsen-Kudsk, Ole Havndrup, Michael Christiansen, Paal Skytt Andersen, Jens Mogensen, Jørgen Kanters, Lars Søndergaard, Keld Sørensen, Flemming Skovby, Stig Djurhuus, Bent Raungaard, Ib Klausen, Peter Riis Hansen, Jim Hansen, Niels Gadsbøll, Egon Toft, Niels Vejlstrup, Henning Bundgaard Kirsten Rasmussen, Odense Universitetshospital, Dansk Selskab for Med. Genetik Ulrik Baandrup, Århus Sygehus, Dansk Selskab for Patologisk Anatomi og Cytologi Øvrige bidragydere Lektor, dr.jur. Mette Hartlev, Forskningsafdeling II, Det Juridiske Fakultet, KU Afdelingslæge Ida Hastrup Svendsen, BBH Klinikchef, overlæge, dr.med. Ulla Feldt Rasmussen, Endokrinologisk afd. PE, RH Overlæge, dr.med. John Vissing, Neurologisk Klinik N, RH

4. Family screening in hypertrophic cardiomyopathy • Our experience; 145 probands – 630 relatives • In Denmark there is ~3 1. degree relatives pr. proband • Gene mutations are found in ½ the families • Based on genetic findings 80% of relatives without significant clinical findings had the “risk” rejected • 99%’s of the relatives accepted the offer of clinical and genetic screening

5. Screening strategy Clinical work-up-diagnostics-treatment – unaltered The new aspect Is it an inherited disease? Yes Family screening; Are there any relatives? Benefit from screening? (Pre-natal diagnostics)

6. Criteria for clinical assessment • The probands diagnose is firmly established • The proband has 1. degree relatives • The relatives are expected to gain from the screening

7. Approaching the relatives • Contact through the proband • Relatives are informed – rationale and expected benefit AND possible ”side effects” • Relatives gives written consent

8. Family screening - content • Clinical work-up - ALWAYS - preceding genetic testing • Genetic testing - IF - the probands mutation has been identified • Genetic counselling

9. Criteria for genetic testing ALWAYS following clinical work-up • One or more relatives are expected to gain from the result • If pre-natal diagnostic / pre-implantation diagnostics may be requested The prerequisite for genetic testing: The probands mutation has been identified

10. Results of genetic testing – follow-up • Positive gene test – follow-up is offered • Negative gene test – follow-up is ceased • No genetic findings – follow-up is offered

11. Genetic counselling By cardiologists – genetic counsellors (prenatal diagnostics, <18 y, others) Neutral information of probands and relatives - prior to screening - during screening - following screening

12. Criteria for genetic counselling • Patients / relatives / gene carriers with inherited cardiac diseases re reproductive counselling (for discussion of prenatal diagnosis incl. PGD) • Parents with children < 18 y (discussion of presymptomatic diagnosis of a child) • When a patient or family request counselling

13. Screening of children? Problem: If the parents make the decision the childs rights to know and rights not to know – may be jeopardised Recommendations: • No genetic testing if the disease does not develop until the age at which the child can make his/her own decision (~15 y) • If the disease is seen in childhood clinical screening is offered from that age • If clinical screening may be false negative - genetic testing is offered – if a positive answer a priori is thought to lead to active treatment

14. Organisation of family screening • Increasing demand from patients and relatives • Homogenous screening availability across DK • Local hospitals and centres need to be involved • Special clinical set-up’s incl. field-workers • Mainly focus on relatives – rather than probands • Expertise in ethic and legal aspects

15. Organisation of family screening • Organisation depending on disease frequency • ? Sharing/dividing diseases between centres • Several speciality-experts are needed • Genetic testing / interpretation is difficult • Develop “evidence while working” in DK

16. Proposed patient-flow • Locally, the indication for family screening is assessed • In the centre the proband is evaluated and the relatives are contacted and offered screening • Following screening the relative with a need for follow-up is offered further management in • In the centre - or • Locally, according to specific arrangements • Conferences and exchange of data between the local department and the centre

17. Rigshospitalets Enhed for Arvelige hjertesygdomme The Heart Centre Department of Cardiology Identification, counselling, dx. work-up and treatment Rigshospitalets Enhed for Arvelige Hjertesygdomme Ledelse / Ekspertgruppe Juliane Marie Centre Clinical Dep. of Genetic Genetic counselling Diagnostic Centre Depart. of Biochemistry Genetic testing Research and development Co-operators and advisers Paediatricians, psychologists, obstetri-cians, forensic medicine, neurologists, etc

18. Take home message 1 = 4 (1 proband + 3 relatives)