Incidental Findings from Genome Sequencing Nuances and Caveats

by Yang Sao Affiliate Marketing You have your genome or exome (the protein-encoding part) sequenced to help diagnose a puzzling set of symptoms, and something totally unrelated, and unexpected, turns up - a so-called "incidental finding."

Surprises, of course, aren't new in medicine. The term "incidental finding" comes from "incidentaloma," coined in 1995 to describe an adrenal tumor found on a scan looking for something else. I had one -- a CT scan of my appendix revealed a polycystic liver. A friend had it much worse. She volunteered to be a control in an Alzheimer's imaging trial, and her scan revealed two brain aneurysms!

Geneticists have long expected an avalanche of incidental findings from clinical (exome or genome) sequencing. Researchers from Baylor College of Medicine and NHGRI and elsewhere described several cases at the American Society of Human Genetics annual meeting last fall. My favorites:

- A boy had his genome sequenced as part of a project to better diagnose syndromes of developmental delay, intellectual disability, and seizures. Researchers found the aorta weakening of Marfan syndrome, gave the boy a repurposed drug in clinical trials, and he's ok.

- A family with several members having their genomes sequenced to evaluate heart disease discovered that their "writer's cramp" is myoclonus dystonia, a neuromuscular disease.

- A man had his genome sequenced in a study to investigate atherosclerosis and learned he had a deafness mutation. Although he claimed he had normal hearing, further testing showed he didn't - he'd adapted so well for so long that he hadn't known he was missing a sense.

To provide guidelines for clinicians having to disclose a medical surprise, the American College of Medical Genetics and Genomics released much-anticipated recommendations on March 21, to kick off the annual meeting.

The most important points come near the end of the 27-page document, especially the table of conditions to be tested for. And while the report is very clear, the accompanying news release uses some fuzzy definitions that often crop up when genetics is simplified. I know from genetic counseling and writing textbooks that misuse of certain terms can confuse. ("Genetic code" for "DNA sequence," and "carrier" in for "pre-symptomatic," when it more traditionally refers to someone who has one recessive allele, and no corresponding illness or trait.) News aggregators that boil down news releases may miss such nuances.

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