American Academy of Pediatrics (AAP) and American College of Medical Genetics (ACMG) recently provided two recommendations about predictive genetic testing of children. The Clinical Sequencing Exploratory Research Consortium's Pediatrics Working Group compared these recommendations, focusing on operational and ethical issues specific to decision making for children. Content analysis of the statements addresses two issues: (1) how these recommendations characterize and analyze locus of decision making, as well as the risks and benefits of testing, and (2) whether the guidelines conflict or (...) come to different but compatible conclusions because they consider different testing scenarios. These statements differ in ethically significant ways. AAP/ACMG analyzes risks and benefits using best interests of the child and recommends that, absent ameliorative interventions available during childhood, clinicians should generally decline to order testing. Parents authorize focused tests. ACMG analyzes risks and benefits using the interests of the child and other family members and recommends that sequencing results be examined for additional variants that can lead to ameliorative interventions, regardless of age, which laboratories should report to clinicians who should contextualize the results. Parents must accept additional analysis. The ethical arguments in these statements appear to be in tension with each other. (shrink)

Whole-genome analysis and whole-exome analysis generate many more clinically actionable findings than traditional targeted genetic analysis. These findings may be relevant to research participants themselves as well as for members of their families. Though researchers performing genomic analyses are likely to find medically significant genetic variations for nearly every research participant, what they will find for any given participant is unpredictable. The ubiquity and diversity of these findings complicate questions about disclosing individual genetic test results. We outline an approach for (...) disclosing a select range of genetic results to the relatives of research participants who have died, developed in response to relatives? requests during a pilot study of large-scale medical genetic sequencing. We also argue that studies that disclose individual research results to participants should, at a minimum, passively disclose individual results to deceased participants? relatives. (shrink)

The law of unintended consequences is generally applied to technological advances that solve one problem but cause another. In this view, the problem created may be worse than that which was solved, hence the law is used as an argument against technological advances. Concern about intent and consequence comes to mind when reading the article by Ronald Green on parental decision making and prenatal genetics. Green's analysis, combined with the realities of genetic practice, raises questions about parental power, eugenics, and (...) the interests of children affected by genetic or congenital disorders. Green proposes rules and draws conclusions that are not useful for clinicians and that promise harm to families and individuals affected by genetic disorders. Green's analysis may be an example of a corollary that could be viewed as the Law of Unintended Ethics.Green's paper begins with an apparently contradictory dual thesis. First, he supports unfettered parental decision making about their fetuses and children. Second, he suggests that we should strive to give our children lives unimpaired by serious genetic disorders. (shrink)

The law of unintended consequences is generally applied to technological advances that solve one problem but cause another. In this view, the problem created may be worse than that which was solved, hence the law is used as an argument against technological advances. Concern about intent and consequence comes to mind when reading the article by Ronald Green on parental decision making and prenatal genetics. Green's analysis, combined with the realities of genetic practice, raises questions about parental power, eugenics, and (...) the interests of children affected by genetic or congenital disorders. Green proposes rules and draws conclusions that are not useful for clinicians and that promise harm to families and individuals affected by genetic disorders. Green's analysis may be an example of a corollary that could be viewed as the Law of Unintended Ethics.Green's paper begins with an apparently contradictory dual thesis. First, he supports unfettered parental decision making about their fetuses and children. Second, he suggests that we should strive to give our children lives unimpaired by serious genetic disorders. (shrink)

An urgent need for standards and guidelines on genetic testing has arisen because of swift advances in research, facilitated by the Human Genome Project. The goals of the Human Genome Project include the identification of all genes and sequencing of the human genome. The project is currently ahead of schedule and under budget. We can expect an avalanche of genetic information, much of which will be relevant to human disease. In addition to the Human Genome Project, investigator-initiated research projects and (...) commercial biotechnology laboratories are discovering human disease genes at a breathtaking pace. Technology transfer has been rapid and has led to the availability of numerous clinical tests within only a few years since the first disease gene yielded to the technique of positional cloning. Disease genes are selected for study for a number of reasons. Genes for rare diseases may be studied before more common disorders because they elucidate an important area of pathogenesis. Unfortunately, technology transfer to the clinic for rare tests is hindered by several factors. Standards need to be established to assure that genetic tests for rare diseases are not ignored or mismanaged in the rush to commercialize tests for more common human genetic diseases. (shrink)