But that’s assuming the information is clear-cut. Here’s where the chess game gets more challenging.
NICU patients not infrequently are born significantly prematurely and often have multiple medical issues. Says Dr. Mróz, who is also director of the core hematology laboratory, Department of Laboratory Medicine and Pathology, “As a pathologist, this is the hardest challenge I have, particularly with those very early preemies.” Those born at around 30 weeks gestation, or sometimes earlier, “tend to have many complex symptoms that straddle the line: Are they related to that heavy prematurity, or do they have some underlying genetic condition that may present in a very similar fashion?” he asks. “Because these very young patients have a lot of processes that are not yet fully matured.”
“This is a very fine line we need to walk,” Dr. Mróz adds. “We don’t want to overcall any of these symptoms. Yet at the same time, we have to make sure we include all the genes that may be relevant and potentially responsible for those symptoms. And I find it, personally, a very, very hard line to walk.” These scenarios, as it turns out, are less line than tightrope, and less walk than an unnervingly brisk trot.
So how do they manage? “It’s hard,” Bower concedes.
Time for a metaphor to come off the bench. “It’s a heavy, heavy team sport,” says Dr. Mróz, who is a member of the CAP/ACMG Biochemical & Molecular Genetics Committee.
here at the New York Genome Center with CEO and scientific
director Bing Ren, PhD. Says Dr. Ren, “The New York Genome Center
is committed to expanding its clinical genome sequencing capabilities
to accelerate the promise of precision medicine and deliver meaningful
impact for patients everywhere.”
At Minnesota, that plays out in internal and external conversations, both formal and informal, with multiple types of providers. It’s also a plus, Dr. Mróz says, that the genetic counselors are clinically active. The pathologists also dig into the patient notes—not just the ones generated for testing, “but diving deeper, looking at the overall prenatal presentations,” he says. And each pathologist has their own subspecialty. “So we can put together a very nice group email or in-person conversation before we even go to the consensus conference where all the pathologists and other team members join” to review cases and hone in on whether a particular variant is compellingly associated with the phenotype and thus merits reporting.
“That enhances how we decide what we’re going to put in the report,” Dr. Mróz says. What’s left out isn’t noise, exactly, but it may be information that’s not acutely relevant to the clinical presentation they’re evaluating. “So that’s a strength of the program, that you bring more than one person to do the final analysis.”
Such meetings not only provide helpful structure about what to report but also are “one of the selling points” of doing the testing in-house, says Bower. “It allows for dynamic back and forth between us and the clinical team about, What is helpful for you? What are you trying to explain in the situation?”
The answer tends to be, like a crying baby, consistent yet fickle: It depends. “You need that dynamic conversation,” Bower says. “We found something here—does this fit with what you see? Is this potentially helpful information? Or is this going to disrupt a very difficult process to throw something uncertain into the middle of the mix?” In some cases, Bower says, clinicians want that slam-dunk answer to what is happening with the patient, nothing more. They’re not interested in learning about the handful of variants that might provide an explanation.
“With the whole genome, there’s no way you can look at 4½ million variants,” says Bower. “You are prioritizing them based on what the clinical team is telling you.”