Recommendations are expected to change the practice of genomic medicine
In a highly anticipated report, landmark recommendations on the handling of incidental findings in clinical genome and exome sequencing are being issued from the American College of Medical Genetics and Genomics (ACMG). A report of the recommendations, led by Robert C. Green, MD, MPH, a medical geneticist at Brigham and Women's Hospital (BWH), outlines for the first time a minimum list of genetic conditions, genes and variants that laboratories performing clinical sequencing should seek and report to the physicians that ordered the testing -- regardless of the original reasons for which the test was ordered.
"If, as expected, these recommendations are adopted by laboratories and clinicians, they will have important implications," said Green, who also co-chaired the ACMG Working Group that developed the recommendations. "As clinical sequencing becomes more widespread, laboratories are looking for guidance on how and what should be communicated to clinicians when results are analyzed. These recommendations will allow a small percentage of families to learn unexpected but potentially life-saving information about an illness they may have never suspected they were at risk for."
The recommendations are the result of a year-long process which included review by outside experts and approval by the ACMG Board of Directors. Leslie Biesecker, MD, chief and senior investigator of the Genetic Diseases Research Branch at the National Human Genome Research Institute co-chaired the working group with Dr. Green.
"Incidental findings" are health-related interpretations of a patient's genetic code that are unrelated to the primary reason for ordering the genetic testing. For example, if a clinician orders exome or genome sequencing to analyze genes related to a patient's cardiac condition, the laboratory will already have information about all the other genes in hand and could examine genes for something like cancer predisposition with relative ease. Should a known or suspected mutation be found in a cancer predisposition gene, the laboratory would report this incidental findings back to the ordering clinician, and the clinician and patient could take steps to screen for cancer. However, in the absence of accepted guidelines about which variants to search for and which results to return to the clinician, laboratories have been uncertain whether to search for or report results beyond those that the doctor ordered.
"We are at an early stage in the implementation of genomic medicine, and this is a difficult topic to manage because there is not yet much scientific evidence to support whether returning incidental findings can provide medical benefit," said Dr. Green. "Based upon existing evidence and clinical judgment, our Working Group of medical geneticists, genetic counselors, ethicists and molecular laboratorians reached consensus that a small number of conditions, genes and variants were likely to have a positive impact on the health of patients and their families if incidentally identified and reported."
In assembling this list, the Working Group prioritized the disclosure of disorders where: