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ASHG Position Statement Provides Guidance for Genetic Testing in Children and Adolescents

NEW YORK (GenomeWeb) – In a position statement on genetic testing in children and adolescents published today, the American Society of Human Genetics pointed to a variety of ethical and other issues arising from such testing, both in clinical and research contexts, and made a number of recommendations.

The report touches on genome-scale, carrier, direct-to-consumer, pharmacogenomic, newborn, and pre-adoption testing, and covers the reporting of secondary findings, adult-onset conditions, incest, and non-paternity results.

ASHG also made suggestions on how to improve professional education in order to enhance providers' understanding of genomic medicine.

The position statement, published by ASHG's workgroup on pediatric genetic and genomic testing in the American Journal of Human Genetics today, is an update of a 1995 joint statement from the American Society of Human Genetics and the American College of Medical Genetics and Genomics on the same topic.

“At that time, we had limited data on how genetic testing affected children and their families, and generally suggested that unless obtaining this data could provide timely medical benefits to the child, testing should be deferred to adulthood,” said Jeffrey Botkin of the University of Utah, the first author of the report, in a statement.

In the meantime, doctors have gained experience with genetic testing in children, while technologies have moved from single-gene to genome-wide analyses with the introduction of chromosomal microarrays and next-generation sequencing.

However, the interpretation of test results remains a challenge. "At the present time, the contrast between our ability to identify genetic variants and our ability to fully interpret the information gives rise to many of the ethical issues in this domain," the authors wrote.

Regarding testing for adult-onset conditions, the ASHG recommends waiting until adulthood, unless a clinical intervention in childhood exists. In some cases, testing might be reasonable, for example, to alleviate psychosocial stress, and it might also be justified for research purposes, they wrote.

Generally, genetic testing should be limited to single-gene analyses or targeted gene panels, rather than comprise whole-exome or whole-genome sequencing, the authors wrote, though limited targeted analyses of genome-scale data is "an acceptable alternative" in some cases. For diagnostics, narrower tests should generally be performed first, and genome-wide test only should be employed if no causative mutation is found. 

Also, genome-scale sequencing is "not indicated for screening in healthy children" at the moment, including genome sequencing for newborn screening, which should only be performed in research settings, according to the report.

With regards to secondary findings, ASHG recommends that they only be disclosed when there is "clear clinical utility" for the child or family members, and only based on informed consent. They should be managed similarly in the context of germline testing and of tumor profiling.

While parents should generally be allowed to decline receiving secondary findings for their children, clinicians should go against these wishes "when there is strong evidence that a secondary finding has urgent and serious implications for a child's health or welfare, and effective action can be taken to mitigate that threat."

In the context of research projects, investigators should follow institutional review board plans for managing secondary findings, but ASHG believes that researchers should not be required to search for such findings in their data, unless it is relevant for their research.

Chromosomal microarray analysis has the same potential for generating secondary findings as DNA sequencing tests and can also reveal consanguinity. It should require informed consent, "a practice that has not been routine for traditional chromosome analysis," the authors pointed out.

Practice guidelines for CMA testing should be developed, along with a list of genes with disease-associated duplications or deletions that should be reported as secondary findings. A similar list if 65 genes already exists for sequencing-based diagnostics testing.

Regarding carrier testing, ASHG "neither recommends nor discourages" offering it to adolescents who ask for it, though carrier testing in children and adolescents should not be performed through institutions, such as high schools or colleges, at this time.

Direct-to-consumer testing, on the other hand, should be "discouraged in children" until DTC companies can assure the quality, accuracy, and validity of their tests and provide adequate counseling. If performed, DTC testing should require parental consent and should not include adult-onset conditions.

Pharmacogenomic testing "might be appropriate" in children in cases where there is clear evidence for its clinical utility, the authors wrote. While it is strongly supported in some areas, for example, TPMT testing prior to thiopurine therapy for childhood leukemia, in other instances, PGx testing can be misleading because some enzymes involved in drug metabolism are "metabolically immature" in children and do not work as predicted from genetic testing.

Newborn screening is "one of the most effective public-health programs of the last century," according to ASHG, but state programs should only add new conditions to their mandated panels "after a thorough review of the evidence on the benefits and harms."

In most US states, newborn screening is mandatory, though parents can opt out for religious or philosophical reasons in 43 states, and ASHG believes this should remain the case, rather than be changed to an opt-in approach.

Many states keep leftover dried bloodspots from newborn screening for quality assurance, a practice that ASHG recommends should continue. In addition, parents should be allowed to authorize the use of dried bloodspots for research.

Additional research on reporting carrier status from newborn screening to parents is needed, they wrote, which could help parents plan future pregnancies.

Some prospective parents have been interested in obtaining genetic test results from a child they might want to adopt. Such pre-adoption testing "should be consistent with the tests performed on all children of a similar age" for diagnosis or disease prevention, and should be limited to childhood diseases, according to ASHG.

Another issue around genetic testing in children is that it can reveal consanguinity of the parents, such as parents who are first-degree relatives. While incest is illegal in most jurisdictions, clinicians are not obliged to report incest between consenting adults, but must report any suspected child abuse, according to ASHG.

Genetic testing may also reveal misattributed parentage, in particular no-paternity, which is relatively common, with estimates ranging from 1 percent to 10 percent of children. ASHG recommends that parents be informed ahead of time about the possibility of detecting misattributed parentage, but that providers should avoid disclosure of such results "unless there is a clear medical benefit that outweighs the potential harms."

Finally, communicating genetic test results effectively is important to avoid misunderstandings, and ASHG recommends that test providers have appropriate training and that labs provide reports that are both detailed and accurate but also "facilitate comprehension by providers."

Genetic testing in children should have a "long-term communication plan for all results," which might not all be reported at the same time. Standards for the storage of genetic data in electronic health records need to be developed, as well as mechanisms for sharing results with other family members.

ASHG also sees a clear need for professional education of healthcare providers about genetic medicine, as well as for improving the public's understanding of genetics.