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The Clinical Sequencing Exploratory Research Consortium’s Pediatrics Working Group compared recent recommendations on predictive genetic testing of children from the American Academy of Pediatrics (AAP) and American College of Medical Genetics and Genomics (ACMG). The group focused on operational and ethical issues specific to decision making for children.1
"The big debate is about the goals of testing, and who decides it," says Ellen Wright Clayton, MD, JD, a member of the work group. Clayton is also Craig-Weaver Professor of Pediatrics and professor of law at Vanderbilt University’s Center for Biomedical Ethics and Society in Nashville, TN.
The position taken in the AAP/ACMG paper is that predictive genetic testing should not be done unless intervention to protect the health of the child is needed before adulthood.2
"A major justification for this position is that children may not want to know when they reach adulthood, a decision many adults make," says Clayton. "They make some cautious exceptions in the case of adolescents who want testing, and serious family distress."
In contrast, a separate ACMG policy statement concerning reporting of "incidental findings" when genomic sequencing is performed as a diagnostic test justifies predictive genetic testing for adult-onset disorders — even when not needed for the child’s personal health care during childhood, in order to make the information available to other family members who may be at risk.3
"They argue, among other things, that there is benefit to the child in having adult relatives not get sick," says Clayton.
Both organizations agree that information on a non-treatable disorder such as Huntington’s disease should not be reported, and that variants should not be reported if it’s unclear whether the disorder would cause problems or if it is not known if the particular variant clearly causes disease.
"What has changed is that for a select group of disorders that you know can cause significant morbidity or mortality, and where if you knew about it, you could take some sort of action, there is a recommendation to test for and report these in children undergoing clinical exome sequencing," says Gail E. Herman, MD, PhD, FACMG, FAAP, president of the ACMG.
The ACMG recommendation is that, for these specific conditions, the benefit to the family and possibly future health of the child outweighs the concern regarding testing a child for an adult-onset disorder. "We would not specifically perform a single gene test in a child for these adult disorders unless they were symptomatic," says Herman. "However, when exome sequencing is performed, the data are there and can be analyzed."
The ACMG now recommends testing for and reporting of 56 disease-associated variants for 24 adult-onset disorders, mostly inherited cancer syndromes and cardiovascular disorders. "It caused a firestorm. Ethicists, lawyers, and some clinicians were very upset about this whole issue," says Herman.
At the ACMG’s March 2014 annual meeting, the recommendations were updated to allow for families to opt out of receiving this information when they give consent for the original genetic testing.4
Incidental findings from the ACMG’s list would likely be reported for 2%-3% of children tested, according to recent studies.5,6 "It’s not huge, but it is still significant as people do more and more of this," says Herman. "We’ve done over 100 clinical exome tests at our own institution. Some of the larger centers have done over 1000 as a clinical test."
Even now, some well-informed families are asking about risks of finding other disorders when this type of testing is performed, reports Herman.
Ethicists should participate on panels that review the results of whole exome and genome sequencing, advises Herman. "They should talk about it to medical students, and to the public, and other providers," she says. "There is a lot of work to be done educating everyone as the technology advances."
The overriding principle of the 16 recommendations in the March 2013 statement, Ethical and Policy Issues in Genetic Testing and Screening of Children, is that the best interests of the child should be the primary standard with which to make decisions, says Jonathan M. Fanaroff, MD, JD, director of the Rainbow Center for Pediatric Ethics at Rainbow Babies & Children’s Hospital in Cleveland, OH.
"From an ethical standpoint, genetic information can provide medical benefits and medical harms, as well as psychosocial benefits and psychosocial harms," he says. When making decisions for others, providers must balance the potential benefits against the potential harms before deciding to proceed with predictive testing, emphasizes Fanaroff.
When the condition being tested for is a childhood-onset condition, the parents are generally able to authorize such testing, along with the assent of the child, it is hoped, if he or she is old enough to do so, he says.
"When the condition being tested for is an adult-onset condition, and there is nothing to be done in childhood that may decrease morbidity, predictive testing should generally be deferred until that child is old enough to choose for themselves whether to get tested," says Fanaroff.
The primary ethical issues, says Clayton, are who defines the best interest of the child and to what extent can the interest of others supersede the child’s interest. "This is very much going to be debated," she says, pointing to a new grant opportunity from the National Institutes of Health to explore the benefit of expanding the definition of "benefit of treatment" beyond the traditional medical model, in the context of newborn screening.
"It’s one thing when you have a family that knows they are at risk. Then you can have a conversation about this," says Clayton. "But to do additional testing, as proposed by the ACMG, is really opportunity screening."
Another issue is how parents can make informed decisions about preventive genetic screening.
"When testing is performed on a child, the choice of whether or not to test at all is taken away from that individual, and this is a significant decision," says Fanaroff. Many adults, when offered genetic testing for untreatable conditions such as Huntington’s disease, choose not to get tested, as they would rather not know the information.
Many patients and family members have very limited understanding of genetics. They may, therefore, underestimate the impact of the decisions they are making with respect to predictive genetic testing, says Fanaroff.
"Bioethicists can help families understand the implications of choosing whether a child gets tested or not, and can help advocate for the best interests of the child," he advises.