Ethics in Medical Genetics

1. Ethics in Medical Genetics Presented by Stephanie Chan, MSc, CGC, CCGC Ophthalmology 601 November 28, 2012 Adapted from an Edmonton Medical Genetics Clinic presentation created by Sajid Merchant, MS, CGC and Tara Dzwiniel, MSc, CCGC

2. What is Ethics? • Establishment of a set of guidelines for morally acceptable conduct within a theoretical framework • Used to help understand the basic themes underlying and governing society’s moral behaviour (common code of conduct)

3. What is an Ethical Dilemma? • An ethical dilemma involves the need to choose from among two or more morally acceptable courses of action, when one choice prevents selecting the other; or, the need to choose between equally unacceptable alternatives (Hamric, Spross, and Hanson, 2000) http://learn.gwumc.edu/hscidist/LearningObjects/EthicalDecisionMaking/index.htm

4. What is Medical Genetics? • A group of medical professionals involved in providing diagnosis, treatment and information on genetic conditions. • Geneticists: MDs involved in examination and diagnosis • Genetic counsellors: Health professionals with specialized graduate degrees and board certification • Provide information and the option of testing to individuals/families with, or at risk for, genetic disorders • Provide supportive counselling to families, serve as patient advocates and refer families to support services • Educators/resource people for other health care professionals and the general public

5. What is Genetic Counselling? Genetic counselling is a communication process... the purpose of which is to help an individual or family comprehend the diagnosis, resources and options available to them For more information: • Canadian Association of Genetic Counsellors (www.cagc-accg.ca) • National Society of Genetic Counselors (www.nsgc.org)

6. Genetics Raises Ethical Issues • Information is familial (non-individualistic) • This raises privacy issues • Implications for reproduction • Effects on future generations • Emotional impact • Predictive value of test results may be limited • Value of genetic information • Knowledge vs. medical benefit • Association with stigmatization

7. Risks of Genetic Testing • Detection of non-paternity • Stigmatization • Including survivor guilt • Insurance, employment, emigration discrimination • Psychological harm • Effect on family members and relationships

8. Framework for Analyzing Cases Principle-based Ethics • Assess the situation • Identify parties involved • Identify ethical problems and considerations (influencing factors and barriers) • Identify principles involved • Decide on course of action based on ethical principles, patient needs, standard practices and the law • Assess outcomes

9. Ethical Principles • Autonomy: Being free to make one’s own decisions (free of coercion)

10. Autonomy Yes. I’ve decided not to be tested. Have you thought about whether you want to take the genetic test? A person’s right to choose freely, based on adequate information, without coercion

11. Ethical Principles • Autonomy: Being free to make one’s own decisions (free of coercion) • Beneficence: Doing the right thing, promoting well-being

12. Beneficence Your risk can be greatly reduced with regular screening and removal of polyps. It’s scary to know that I have such a high risk of colon cancer. Acting to improve patient welfare

13. Ethical Principles • Autonomy: Being free to make one’s own decisions (free of coercion) • Beneficence: Doing the right thing, promoting well-being • Nonmaleficence: Doing no harm

14. Nonmaleficience Let’s discuss those issues. I want my daughter to have genetic testing. Do no harm

15. Ethical Principles • Autonomy: Being free to make one’s own decisions (free of coercion) • Beneficence: Doing the right thing, promoting well-being • Nonmaleficence: Doing no harm • Justice: Being fair, equal benefit/burden distribution • Rule of Fidelity: To keep all contracts and promises • Rule of Veracity: To tell the truth, be honest • Rule of Confidentiality: To not disclose information shared in an intimate manner • Rule of Privacy: To respect limited/restricted access to a person

16. Other Ethical Dilemmas in Genetics • Right to know/right not to know • Duty to warn/inform • Duty to re-contact • Testing without informed consent • Adoption issues • Pre-adoption testing, post-adoption duty to warn

17. Preventing Ethical Dilemmas in Clinical Practice • Detailed genetic counselling! • Attempt to anticipate dilemmas that may arise and address them upfront with patient • ie. non-paternity may be revealed, risks apply to other family members, disclosure of information to family, physicians, insurance • Informed consent • Keep current on published policies

18. Examples of Ethical Dilemmas About Genetic Testing Throughout the Lifecycle • Preconception/Prenatal • Request for gender selection for non-medical reasons • Request prenatal testing for adult-onset conditions • Request testing in order to have an affected child • Childhood/Adolescence • Parents request predictive testing for adult-onset conditions • Adulthood • Adult child requests testing for adult-onset condition when parent’s status is unknown

19. Case examples What do you do if…?

20. Case 1: Predictive Testing for Huntington Disease • Julie is 25 years old and is requesting predictive genetic testing for Huntington Disease, a fatal neuro-degenerative condition that led to her paternal grandmother’s death at age 65. • Julie’s 45 year-old father is alive and well and is not interested in genetic testing for this condition. Should Julie be offered testing?

21. Case 1: Facts • Autosomal Dominant Inheritance (50% chance to inherit from an affected parent). Therefore: • Father’s risk is 50% • Julie’s risk is 25% • Possible test outcomes: • If Julie is positive, Father’s risk becomes 100%, sibling’s risk becomes 50% • If Julie is negative, Father’s risk remains at 50%, sibling’s risk remains at 25%

22. Case 1: What is the ethical dilemma? Julie’s right to decide to have testing to determine her own status VS Her father’s right NOT to know certain information about himself

23. Case 1: Should Julie be offered testing? Julie is 25 years old and is requesting predictive genetic testing for Huntington disease, a fatal neuro-degenerative condition that led to her paternal grandmother’s death at age 65. Julie’s 45 year-old father is alive and well and is not interested in genetic testing for this condition. Autosomal dominant inheritance (50% chance to inherit from an affected parent). Therefore: Father’s risk is 50% Julie’s risk is 25% Possible test outcomes: If Julie is positive, Father’s risk becomes 100%, sibling’s risk becomes 50% If Julie is negative, Father’s risk remains at 50%, sibling’s risk remains at 25%

24. Case 1: Direct-to-consumer testing Julie learns about a private company offering genetic testing for Huntington disease on a cheek swab She does not need a health care professional to order this test for her Is this a good thing or bad thing?

25. Case 1: New dilemma! Julie was tested and found to be positive for the genetic mutation that causes Huntington disease. She is now pregnant and requests prenatal diagnosis for Huntington disease. She states that termination is not an option regardless of the test result. Should you facilitate testing?

26. Case 1: A different condition What if it was autosomal dominant retinitis pigmentosa? • Variable age of onset but tend to be later with better vision retention than other types of RP, variable pattern and degree of visual loss (expressivity and reduced penetrance) Blindness vs fatal neurodegenerative condition

27. Case 1: Should Julie be offered testing? Julie is 25 years old and is requesting predictive genetic testing for ADRP, an often blinding condition her paternal grandmother had been diagnosed with at age 55 Julie’s 45 year-old father is alive and well and is not interested in genetic testing for this condition. Autosomal dominant inheritance (50% chance to inherit from an affected parent). Therefore: Father’s risk* is 50% Julie’s risk* is 25% Possible test outcomes: If Julie is positive, father’s risk* becomes 100%, sibling’s risk* becomes 50% If Julie is negative, father’s risk* remains at 50%, sibling’s risk* remains at 25% *risk to carry mutation

28. Case 2: Juvenile X-linked Retinoschisis • David is 24. He had a retinal detachment in his left eye at age 12 and now has significant central and some peripheral vision loss. • Growing up with David, his sister Amanda (now 28) witnessed the impact this condition had on his life • Amanda would like to know her carrier status as she wants PND and would terminate an affected fetus • David refuses to undergo genetic testing to determine the mutation he carries, mother is unavailable for testing

29. Case 2: Facts • X-linked Recessive Inheritance (50% chance to inherit from a carrier mother). Therefore: • Amanda’s risk is as high as 50% assuming that their mother is a carrier • Possible test outcomes: • If Amanda is positive, she will be aware of her carrier status and would also know David’s genetic mutation indirectly • If Amanda is negative, it’s an equivocal result (may not have looked at the correct gene, unlikely)

30. Case 2: What is the ethical dilemma?

31. Amanda would like to know her carrier status as she wants PND and would terminate an affected fetus Her brother, David (affected) refuses to undergo genetic testing to determine the mutation he carries and their mother is unavailable for testing X-linked Recessive Inheritance (50% chance to inherit from a carrier mother). Therefore: Amanda’s risk is as high as 50% assuming that their mother is a carrier Possible test outcomes: If Amanda is positive, she will be aware of carrier status and would also know David’s genetic mutation indirectly If Amanda is negative, it’s an equivocal result (may not have looked at the correct gene, unlikely) Case 2: Should Amanda be offered testing?

32. Case 3: Leber Congenital Amaurosis • Affected 3 year old • Severe/early vision loss, nystagmus but with clinical heterogeneity • Parents are planning to have more children and are willing to consider termination to avoid having more affected children

33. Case 3: Facts • Autosomal recessive inheritance pattern (25% chance next pregnancy is affected) • Genetic testing requested on child’s blood sample • Heterozygous RPE65 mutations identified in child • Carrier testing in parents result in mom carrying one mutation and dad not carrying the other mutation Do you tell the family of the results? If so, how?

34. Case 3: What is the ethical dilemma?

35. More considerations

36. When Should Genetic Testing be Considered for Children? • Consider the age of onset of the condition and • Are there any effective interventions? and • Can the test can be adequately interpreted? • Examples: retinoblastoma, aniridia, choroideremia, MEN 2A and 2B (standard of care), FAP, VHL ASHG/ACMG Report. Am J Hum Genet 57:1233, 1995

37. Special Issues in Testing Minors • Respect child’s autonomy • Provide informed consent/assent, considering: • intellectual capacity and developmental stage • family dynamics (eg, fragile child syndrome, parent bonding) • Consider implications for: • family-planning decisions by parents/the child in the future • management of potentially affected siblings in childhood ASHG/ACMG Report. Am J Hum Genet 57:1233, 1995

38. Other Ethical Considerations Emerging duties may include: • Duty to re-contact: Following up and re-contacting patients if new information becomes available • Invite patient to contact clinic should any relevant changes occur (new information from relatives) and for testing/research updates • Warning of risk to others

39. Legal Opinions Issue: Warning other family members • Pate v Threlkel (Florida, 1995) • Ruling: Duty to warn is satisfied by warning patients that their family members may be at risk for cancer • Safer v Pack (New Jersey, 1996) • Ruling: Physician has a duty to warn other family members that they may be at risk

40. Ethical, Legal, and Social Issues in Genetic Testing: Key Points • Anticipate and discuss potential ethical, legal, and social issues before testing • Encourage family involvement and a shared approach to decision making • Take care to avoid coercion by relatives or health care providers • Stay informed about state and federal laws to prevent genetic discrimination and protect privacy

41. Summary • Ethical issues are common in genetics because of the nature of genetic information • Necessary to fully consider all sides of the situation and the effect on all individuals before making a plan of action

42. More Clinical Scenarios • Julie has an identical twin, also your patient, who had chosen not to take the test. • Would you warn her of the risk? • What if the twin is fraternal (non-identical)? • New scenario: Julie’s dad received a negative test result, but had not given you permission to disclose this to other family members. • Would you still offer the test to Julie? • What would you tell Julie about her risk of HD?