Imagine getting a chest X-ray to identify the cause of a serious cough. The radiologist finds a shadow that wasn’t causing the cough but could be a tumour. In many cases, it is obvious what to do upon uncovering these sorts of secondary or incidental findings — most doctors would follow up on the search for a possible lung tumour, for example.
But genomic information presents a special case: genes are predictive, but not perfectly so, making some results murky. And many genetic diseases and predispositions to disease don’t have clear and obvious paths for clinical management, potentially making them a lifelong psychological burden.
Today, the American College of Medical Genetics and Genomics (AMCG) released recommendations for how genome-sequencing laboratories should report incidental findings after a doctor orders a full or partial genome sequence. It defines a minimum list of about 60 genes and 30 conditions that should be reported to the doctor as part of a patient’s care, whether the patient wants to know them or not. But the guidelines stop far short of recommending that all risk factors be passed on to doctors and patients.
From gene variants that cause malignant hyperthermia susceptibility to the BRCA1 and BRCA2 variants associated with breast and ovarian cancers, there are some well-established links for conditions that can be managed or monitored clinically. The ACMG recommends treating children no differently from adults, and leaves the responsibility of passing the information on to patients to the ordering clinician. As with a suspicious shadow on an X-ray, “it is up to the ordering clinician to contextualize those findings,” says Robert Green, a medical geneticist at Brigham and Women’s Hospital in Boston, Massachusetts, and the co-chair of a working group that has been refining the recommendations for more than a year.
Few, if any, countries worldwide have developed such specific guidelines. “This is a pioneering effort,” says Muin Khoury, who heads the office of public-health genomics at the US Centers for Disease Control and Prevention in Atlanta, Georgia. And there is a need.
The number of personal genomes ordered for clinical purposes to date is probably in the hundreds or thousands, but with the cost of genome sequencing dropping rapidly and the number of companies vying to interpret genome data rising, ‘prescribing’ genomes to patients could become a regular practice, and such recommendations may inform the standard of care.
Some argue that the recommendations are too conservative. A document describing them — released today at the annual meeting of the ACMG in Phoenix, Arizona — notes that the working group tried to strike a balance between what it calls genetic libertarians, “who feel that patients have the right to full and complete accounting of all possible risks,” and genetic empiricists, who believe that data do not support most disease–gene associations and that “it is irresponsible to create the psychological burdens of being a ‘patient in waiting.’ ”
Gholson Lyon, a geneticist at Cold Spring Harbor Laboratory in New York, says that the document is “biased heavily” in favour of the empiricists and restricts the ability to analyse the millions of genomes that could come online in the coming years and support research.
Nancy Spinner, chief of the division of genomic diagnostics at the Children’s Hospital of Philadelphia in Pennsylvania, says that the recommendations are helpful and thoughtful on the complexities of the situation, even though they differ in some ways from her own team’s practice. Her team does not give back results for children if the risk factor is for adult-onset conditions. “We have a little more of a conservative approach,” she says.
The recommendations pertain only to clinical sequencing and not to research or sequencing for healthy people. Also, says Green, they are a work in progress. The list of genes and disorders may expand or contract on the basis of how clinicians and patients respond. “We tried to imagine a world in which a lot more people are going to be sequenced. I don’t know if we’ve gotten it right, but I believe we’ve put a lot of effort into a reasonable first step.”
The headline of this story has been changed to reflect the fact that ACMG has issued recommendations, not guidelines.