Ethic and Genetics

1. Ethic and Genetics Pr. Didier LACOMBE Head Dept. Medical Genetics National Reference Center for Birth Defects CHU de Bordeaux Université Bordeaux 2 IV° French-Chinese Bioethics Conference Bordeaux 8-9/04/2010

2. Department of Medical Genetics Roles : diagnosis of a genetic disease And what’s around the diagnosis : - Care of the patient, familial support - Genetic counseling - Familial screening - Prenatal diagnosis - Presymtomatic diagnosis Medical Genetics = Family involvement

3. Genetic Counseling Information of proband and family : * Disease characteristics : natural history, features, evolution, complications... * Heredity (mode of inheritance) * Recurence risk * Genetic testing possibilities * Screening and prenatal diagnosis possibilities

4. Familial Screening • Screening for heterozygous status of recessive or X-linked conditions (mostly) • Affected child Familial cascade screening • Transmission of information via patient/family, not via doctors to concerned persons (avis 76 du comité consultatif national d’éthique pour les sciences de la vie et de la santé)  • Information via Biomedical Agency (letter) ?

5. Familial Screening • Informed free consent (Code de la Santé Publique - Art. R1131-5) • No discrimination because of genetic characteristics (Code Civil - Art. 16-13) • No insurance or work implications, no obligation of genetic testing (Code de la Santé Publique - Art. 1141-1)

6. Prenatal Diagnosis (PND) • Positive family history and gene mutation identified (~ 2000 disease-causing genes) • Risk → Knowledge (affected or not) • France: PND for severe and non treatable diseases at the time of diagnosis • Genetic counseling visite before PND (article L.2131-1 du code de la santé publique) • Final decision to parents for medical abortion

7. Prenatal Diagnosis • In France PND via Multidisciplinary Centers agreed by Agence de Biomédecine • Medical abortion legal up to the end of the pregnancy • Decision from the couple • Psychological support

8. Preimplantatory Diagnosis (PIP) • Genetic testing on 1/2 cells before uterus transfert of healthy embryos • Avoiding of potential medical abortion (MA) • Couples with multiples MAs • Indication of in vitro fecondation • PND/PIP: acceptability for late-onset genetic diseases ? (cancer predisposition …)

9. Presymptomatic Diagnosis • Definition (P.Harper, 1997) = situations where an abnormal result indicates that the disease will almost develop at some point in life. • New Genetic Medicine: - High risk asymptomatic persons (~ 50%) for genetic disease - Late-onset disorders - Monogenic mendelian disorders

10. Presymptomatic Diagnosis • Knowledge of genetic status of asymptomatic individuals at risk for developing an identified genetic disorder • Concerned persons : - at risk - adults - asymptomatic (absent features) - volontary consent

11. Presymptomatic Diagnosis • Key notion of medical benefit • 2 different situations : • - Possible preventive/curative treatment (ex: cancer predisposition) • No preventive/curative treatment available (ex: neurodegenerative disorders) Model = Huntington disease

12. Presymptomatic Diagnosis Ethical principles (WFN, Neurology, 1999) : • Benefit • Adulthood (independence) • Freedom • Engagement • Confidentiality • Equality • Right of not-knowing

13. Presymptomatic Diagnosis • France (Décret 2000-570) : conditions of prescription of genetic testing • Multidisciplinary teams (Ministry of Health) HD: geneticist, neurologist, psychologist • Care and testing (4-6 months) protocols • Illegal in children without medical benefit

14. Presymptomatic DiagnosisJustifications • To relieve uncertainly about genetic status 54 % • To plan a family 14 % • To plan for the future 13 % • To inform the children 14 % • To be sure one is carrier 2 %

15. Presymptomatic DiagnosisRemarkable events • Pregnancy 20 % (50 % PND; 50 % MA) • Serious adverse events: - Psychological distress and depression 9 % - Psychiatric hospitalization 2 % - Suicide attempt 0 %

16. Presymptomatic DiagnosisConclusions • New concept • Molecular genetic advances : activity • 2 care levels: - Severe diseases : HD model SCA, hereditary dementia/Alzheimer - Mild diseases : CMT, FSH, myotonic dystrophy

17. Genetic Testing in Children • Information, free choice, consent : not possible in children, choice of the parents • Possible in symptomatic children (CF, DMD ..) • Possible: medical benefit in asymptomatic child: - curative/preventive treatment: cancer predisposition syndromes (APC, Gorlin …) - screening/follow-up (Steinert, glaucoma …) - professional/social orientation (CM, CMT …)

18. Genetic Testing in Children Genetic tests forbidden in asymptomatic child : • Severe late-onset genetic disorders - Hereditary cancer predisposition (BRCA1, BRCA2, HNPCC …) - Neurodegerative late-onset diseases (HD, SCA, CADASIL …) • Recessive heterozygous status • Multigenic/polyfactorial heredity

19. Genetic Testing in Children • Personal benefit for the child • Preventive/curative treatment for the family • Deprivation of the right of not-knowing • Breakdown in the child-parents relationship • Disease anticipation

20. Prescription of genetic testing:Difficulties • Lack of specific information before clinical use (genetic counseling) • Random genetic predisposition identification (CGH-array and cancer predisposition) • Presymptomatic testing • Minor children • No individual medical follow-up

22. Free access to genetic testing(autotests via internet) • No medical follow-up (indication, interpretation ..) • No medical indication/interest • No ethic or juridic guide (identity, consent, child ..) • No technical guide (fiability, quality ..)

23. Thanks