Lecture 21: Ethical and practical issues in genetics

Learning outcomes:

  1. Know the principles of biomedical ethics

    • Respect for individual autonomy

      • Safeguarding an individual’s right to control their own medical care and medical information, free of coercion.

    • Beneficence

      • Doing good

    • Nonmaleficence

      • Not harning, preventing harm

    • Justice

      • Ensuring that all individuals are treated equally and fairly

  2. Discuss key ethical issues in medical genetics

    • Genetic testing

      • Prenatal diagnosis, especially for non-disease traits or sex—is it appropriate to test for traits not related to disease?

      • Testing asymptomatic adults for genotypes that predispose to late onset disease

      • Testing asymptomatic children for genotypes that predispose to adult onset diseases—if there’s nothing you can do when the child is young, should parents have access to this info?

      • Secondary and incidental findings and the right “not to know” about clearly deleterious variants that will cause disease that could be prevented if the risk were known—predispositions to cancer

    • Privacy of genetic information

      • Duty to warn and permission to warn—non-directive counseling

      • A patient’s desire to have medical information kept confidential is one facet of the concept of patient autonomy, in which patients have the right to make their own decisions about how their individual medical information is used and communicated to others.

      • Genetics, however, more than any other branch of medical practice, is concerned with both the patient and the family.

      • A serious ethical and legal dilemma can arise in the practice of genetic medicine when patients’ insistence that their medical information be kept strictly private restrains the geneticist from letting other family members know about their risk for a condition, even when such information could be beneficial to their won health and heath of the their children.

      • Judges have ruled

      • Ask before the test begins if they’d like to know about secondary findings

      • If you don’t tell them about something they wanted to know, they can sue.

      • In the US, the primary set of regulations governing the privacy of health information, including genetic information, is the Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA).

      • The HIPAA rule sets criminal and civil penalties for disclosing such information without authorization to others, including other providers, except under a defined set of special circumstances.

    • Misuse of genetic information

      • Insurance/employment discrimination based on an employee’s genotype

      • Discrimination in life and health insurance underwriting based on a person’s genotype—GINA

    • Genetic screening

      • Misuse and distrust of newborn screening programs

      • Privacy

    • Prenatal genetic testing

      • For some hereditary disorders, prenatal diagnosis remains controversial, particularly when the diagnosis leads to a decision to terminate the pregnancy for a disease that causes various kinds of physical or intellectual disabilities but is not fatal in infancy.

      • Prenatal diagnosis is equally controversial for adult onset disorders, particularly ones that may be managed or treated.

      • The dilemma lies in attempting to balance, on the one hand, respect for the autonomy of reproductive decision making about the kind of family they wish to have versus, on the other hand, an assessment of how aborting a fetus affected with a disability might be viewed by the broader community of persons with a disability.

      • When it comes to disorders more related to outward appearance, sex preferences, or other traits, where is the line crossed that decides a trait is serious enough to warrant prenatal testing?

    • Genetic testing for predisposition to disease

      • The ethical principles of respect for individual autonomy and beneficence are central to testing in this context.

      • At one end of the spectrum is testing for late onset, highly penetrant neurologic disorders, such as Huntington’s.

      • For such diseases, individuals carrying a variant allele may be asymptomatic but will almost certainly develop a devastating illness later in life for which there is currently little or no treatment.

      • For these asymptomatic individuals, is knowledge of the test result more beneficial than harmful, or vice versa?

      • The balance for or against testing of unaffected, at risk individuals shifts when testing indicates a predisposition for a disease for which intervention and early treatment are available.

      • For example, in hereditary breast cancer, patients carrying various pathogenic variants for BRCA1/2 have a 50%-90% chance of developing breast or ovarian cancer.

      • Identification of heterozygous carriers would be beneficial because individuals at risk could choose to undergo more frequent surveillance or have preventative surgery.

    • Genetic testing of asymptomatic children

      • Ethical issues in the testing of asymptomatic individuals take on a further degree of complexity when such testing involves minors, particularly children too young to give assent.

      • Testing asymptomatic children for alleles that predispose to disease can be beneficial, even life saving, if interventions that decrease morbidity or increase longevity are available.

      • Children’s autonomy—their ability to make decisions for themselves about their own genetic constitution must also now be balanced with the desire of parents to obtain and use such information.

      • Most bioethicists believe that predictive pediatric genetic and adult onset testing should generally be deferred until a child is sufficiently mature, unless an intervention in childhood would reduce mortality or morbidity.

    • Secondary findings

      • Another area of controversy has arisen in patients who have given consent for exome or whole genome sequencing to find a genetic basis for their undiagnosed diseases.

      • In the process of analyzing an exome or genome, however, pathogenic variants may be discovered incidentally in genes known to be associated with diseases unrelated to the phenotype for which the sequencing test was originally conducted.

      • If the pathogenic variants uncovered as incidental findings cause serious diseases that can be prevented, than is there benefit of drawing up a list of genes that every lab doing ES/WGS would deliberately analyze in every patient, even though they are not relevant to the primary goal of finding the genetic cause for a patient’s unexplained disease?

      • Pathogenic and likely pathogenic variants in this list of genes would be secondary findings that would be sought regardless of whether the patient wishes to know these results, because the patient’s providers deem the benefit of knowing is so compelling for the patient’s health that it outweighs the requirement of patient autonomy.

      • The ACMG has drawn up a list of secondary findings that a lab should seek. It currently includes 73 genes, most of which are involved in serious hereditary cancer and cardiovascular syndromes that are life threatening, not readily diagnosable before the onset of symptoms, and preventable or treatable.

      • The current ACMG recommendation is that patients should be provided with appropriate counseling and then given the opportunity prior to testing to agree or refuse to have such secondary findings looked for and reported.

  3. Given a scenario, be able to identify key ethical issues that are at play

  1. Know the basic considerations for variant interpretation

  1. Be able to interpret a variant found through genetic testing

Key terms:

Beneficence

Maleficence

Informed consent

Permission to warm/duty to warn

HIPAA

Variant interpretation

Variant of Uncertain significance