HG501 — Ethics Cases December 10^th, 2001

During lecture some of these cases will be presented, discussed, and debated between Drs. Petty and Gelehrter.

You should review these cases prior to class, answer the following questions, and be ready to actively participate in class discussion.

In addition, you should read the assigned text prior to lecture.

Case 1: Difficult Decisions about DNA Results for Dad's Renal Transplant

A 45 yo man in end-stage renal failure has adult polycystic kidney disease due to a mutation in the APKD1 gene. He comes to renal transplant clinic for evaluation and learns that his best chance for an excellent outcome will be with a kidney transplant from a living related matched unaffected donor. He has not been an active member of his immediate biological family for the past 5 years, but easily organizes organize family members for typing and DNA linkage testing to determine which individuals are eligible donors. After providing informed consent all participants in the linkage study agree to testing knowing that test results will be provided to them. the patient, and his doctors. All participating family members are very willing to donate their kidney if they are eligible. The patient pays $4200 for linkage analysis and genetic counseling visits for all participating family members. An unaffected daughters in not a good match. Both of his sons, Sam and Seth, 22 yo fraternal twins, are good matches. DNA linkage analysis reveals that Seth, however, has a 95% probability of having inherited the disease mutation. There is a 98% chance that Sam did not inherit the mutation. Sam and Seth are given results individually. On initially hearing his results, Sam understands that he is the only eligible living related donor. He says he is very willing to donate a kidney. Sam and Seth are then counseled together. Seth wonders who will be able to donate him a kidney when he needs one as he wasn't planning on having children. Sam is upset thinking that his brother could die from this disease especially knowing he would be a suitable donor for his brother. Sam quickly changes his mind about donating a kidney to his father. He wants to keep his kidney in case Seth needs it someday. He is much closer to Seth than to his father. He notes, however, he will be unable to tell his father this.

He requests that his test results be removed from the family genetic testing report that is supposed to be provided to his father and father's doctors. He wants to tell his father that both he and Seth probably inherited the mutation and therefore neither can donate a kidney. Seth is very grateful. They request that the geneticist "go along" with this plan.

What do you see as the options for documenting the test result?

What are your obligations as the geneticists caring for the father?

What are your obligations to the Sam?

Does it matter that Sam's testing was originally done for his father's medical care and records for which he gave informed consent?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 2: Ethical Issues Surrounding Uses of Preimplantation Genetic Diagnosis

A couple has a two-year old boy who develops Fanconi's anemia, an autosomal genetic condition that has some congenital anomalies and may be associate with severe life threatening anemia. Despite trials of the most effective therapies for this disease, he continues to have problems. The parents are told that he will need a bone marrow transplant within the next year and a half if he is going to have any chance to survive. All family members are typed to see if they are a match for a bone marrow transplant. No individuals are. The bone marrow registry is contacted to see if there are any appropriate matches in the entire bone marrow registry. There are none. Although the transplantation could be done with an unmatched donor, there would be multiple problems expected. The parents decide they would like to use assisted reproductive technology to achieve a pregnancy of a child that they know would be a matched donor. Specifically, they choose to use in vitro fertilization where fertilization of the egg will take place in a laboratory. At approximately eight-cell stage of embryogenesis, one cell will be examined from each embryo that has been created in a laboratory to determine which of these embryos would be a perfect bone marrow match for their son using preimplantation DNA diagnosis. They also want to use preimplantation diagnosis to assure that this baby does not have the same disorder. Embryos that are a good match and do not have the disease will be placed in the uterus. What questions does this raise?

You are the obstetrician that the couple consults for help.

What do you understand as the options for this family?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 3: Prenatal Testing: What if Mom Must Know and Dad Declines?

A woman is five weeks pregnant and interested in having her fetus tested for Huntington Disease (a later-onset progressive autosomal dominant incurable neurological disorder). Her 35-year-old husband, the baby's father, is at 50% risk of having inherited the condition from his mother. He has previously received genetic counseling from you regarding his 50% risk and predictive DNA mutation testing. He elected not to undergo predictive DNA testing, as he did not want to know if he inherited the mutation as there was no cure or preventive therapy. His wife, however, is seeing you independently for genetic testing of their fetus with intent to abort the fetus if an HD mutation is found. She requests this testing be done without any involvement of her husband who does not know she is seeing you. You realize that testing her fetus may give her information about her husband's mutation status.

You have provided genetic counseling to the husband in the past and are now confronted with a difficult choice related to the requests of his wife for HD testing of their fetus.

What do you see as the options for this mother?

What are your obligations as the geneticists caring for the mother?

What are your obligations to the husband?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 4: Disclosure about Down Syndrome Risks: Doctor's Duties and Decisions

A man has a child with Down syndrome due to an unbalanced translocation of chromosome 21 and another autosome. Upon testing him and his wife you find out that he is a balanced translocation carrier which you thought was likely given the fact his mother had several miscarriages. He does have several younger sibling of child bearing age who are at risk of having the same balanced translocation and therefore of having an increased incidence of miscarriages and the chances of having a live born child with a chromosomal disorder. Given this you recommend he share this information about the translocation with his first-degree relatives. He notes he will not do this as he already has a strained relationship with other family members. He notes they can find out the same way he did.

You are surprised by his reaction s you suspected he would agree with you that it would be important for other family members to know this information.

What are your obligations to your patient?

What are your obligations to other family members?

What are the conflicting ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 5: Are you my daddy?

A couple has a child with very severe cystic fibrosis. The child is homozygous for a three base pair deletion (delta F508) in both copies of her CFTR gene. During the next pregnancy the couple undergoes prenatal testing for CF, as they want to avoid having a child with severe childhood CF. This fetus is a compound heterozygote for one delta F508 allele and a different CF mutation usually associated with a relatively mild form of CF even when seen in a compound heterozygous state with delta F508. The reported phenotype most often associated with this genotype has been male infertility and some pulmonary symptoms in adulthood. Children are usually healthy. Given that neither parent has mild symptoms of CF or infertility; however, a sample mix-up or non-paternity is suspected. The laboratory requests samples from the parents to check results. Both parents are heterozygous for one normal allele and the delta F508 allele. Neither has the other mutation identified in the fetus. Further testing done in the laboratory to make sure there wasn't a sample mix-up or technical problem with the analysis confirms non-paternity. The parents are scheduled to come to clinic together regarding these test results and plan to schedule a pregnancy termination if the fetus is predicted to have CF symptoms like their other child.

What is the best way to handle this that would provide parents with accurate results from which they can make an informed decision regarding pregnancy termination?

What are your options?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 6: Problematic Phenylalanine Levels in Pregnancy

A 30-year-old woman with PKU wants to have a baby. Due to poor parental compliance with a low phenylalanine diet during her infancy and early childhood, she is mildly mentally retarded (IQ — mid 60s) with recurrent psychiatric problems including poor impulse control and attention deficit disorder. She dropped out of a special education program in school. She has had intermittent part time job at K-Mart since then. She lives with her parents in a socially and economically deprived environment. Her father is an unemployed alcoholic. Her 19 yo boyfriend thinks it would be "cool" to be a dad. He is unemployed, has a longstanding history of drug abuse, and has been in and out of jail. He thinks a baby might help him "settle down". They receive extensive counseling about the risks of having a baby with maternal PKU syndrome (congenital cardiac defect, microcephaly, and mental retardation). She is instructed that she must maintain a low phenylalanine level to protect her fetus. She notes she will really try but states she won't give up cheeseburgers and fried chicken. She also notes that the PKU formula really stinks. She is put on a low PHE diet including the formula prior to pregnancy. Due to poor compliance her PHE levels drop only slightly, remaining in the range where there is a high probability of teratogenicity to the fetus. Despite this she becomes pregnant and is insistent on having her baby.

You are concerned about the well being of both the fetus and the mother. You have done as much counseling and education as possible and even see her once a week, but unfortunately with minimal impact. You realize the high potential for a negative outcome on the fetus.

What are your obligations to the fetus? To the mother?

What are your options as the physician caring for the mother and the fetus?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 7: Even if They Didn't Ask Me About EDS, Should I Tell Them What I Suspect?

You are a stellar fourth year medical student going into Pediatrics who absolutely excelled in your 1^st year medical genetics course. Over the recent break you had Thanksgiving dinner with one of your medical school classmates and her family. You meet her 14-year old nephew and noted he had bluish/gray sclera, lots of bruises, and fairly translucent skin. While playing Frisbee with him you were struck by his extreme joint flexibility. You comment on his bruises and he notes that he has always bruised very easy but especially now that he made the varsity gymnastics team as only a freshman and has started practicing with the team. You suspected he might have a connective tissue disorder and could be at risk for severe internal complications. You mention this to your medical student friend, the boy's aunt, who is going to be a neurologist and unfortunately, skipped any lectures on connective tissue disorders. She is consequently not at all struck by his phenotype - after all, he is neurologically normal. She says that her brother, the boy's father, had similar features when he was little but that he was very healthy. He unfortunately died from surgical complications after a bad car accident a few years ago when he was only 29 yo. She also notes there are no genetic diseases in the family but that she doesn't know much about her father's family since her dad died when she was only 3 years of age from some sort of internal bleeding problem.

You feel this child might have an undiagnosed genetic disorder, specifically the vascular type of EDS, that his mother should know about.

What are your responsibilities and limitations?

What are the ethical issues that need to be considered in this case?

Where do you stand on the issues?

Case 8: DNA Testing in Healthy Children: Does Doctor Know Best?

A 30 yo woman wants her 4 yo and 6 yo daughters tested to see if they are carriers of a Fragile X mutation as their profoundly retarded brother has the condition. She notes since she doesn't believe in pregnancy termination but at the same time, she would not want her daughters to have a child who has Fragile X syndrome. Therefore, she would like to know if either daughter is a carrier so she can start trying to influence them at an early age to consider either not having children or adopting children. She would make sure teachers and parents of their friends were sensitive to a positive test result so they wouldn't ask a daughter who carrier a mutation the kind of typical questions about 'having children' or 'being mothers' that she remembers being asked by adults as a young girl. She notes both daughters are excelling in their school programs — both starting reading at only 3 years of age. Neither has any medical or developmental problems.

The geneticist tells the mother that there is no medical indication for testing and it would be best to wait until the daughters can give informed consent for or, at least, assent to testing. Specifically, he discusses the reasons why testing is not recommended in healthy young girls. He notes that testing is only recommended when girls have developmental problems or when they are considering pregnancy and/or are old enough to become pregnant. Mother demands they be tested. Again, the physician notes that there is no medical reason to do testing at this time. He also notes some concerns about testing in girls this age as there could be psychosocial consequences especially if others end up treating them differently because of the testing. Mother leaves very dissatisfied.

Do you think the doctor made the right decision?

What are the risks and benefits of testing?

Does the mother have the right to have the daughters tested?

What are the ethical issues here?

She returns to the clinic 2 months later to see a different doctor. In the clinic staff room the doctor who originally saw them notes they are on the schedule. He sees that his partner is filling out laboratory requisition forms for fragile X testing for both girls. He learns that the mother told his partner that the girls need testing as they both have had significant learning problems this year and are falling behind due to delays. She noted that she and the teachers are quite concerned that they may have Fragile X syndrome. Thus, this physician felt that testing was warranted and is ordering the tests. The first doctor feels that this testing is very inappropriate and feels that the mother is manipulating the system. He tries to convince his partner not to do the testing. The partner feels that if they were his daughters, he'd probably want to know, too, and he personally sees nothing wrong with the testing even if the mother fabricated a story in order to get testing done.

What new issues are raised?

Whose side are you on? Why

Should there be standard guidelines that all physicians follow in such cases?