A broad genetic test saved one newborn’s life. Research suggests it could help millions of others

CINCINNATI (AP) — Brynn Schulte almost died twice as a child, at one point needing emergency surgery for massive bleeding on the brain.

No one knew what was wrong until a test that looked at her complete genetic pattern found a rare bleeding disorder called factor XIII deficiency – an early diagnosis that saved her life.

“You get this hopeless feeling when you don’t really know what’s going on,” said her father, Mike Schulte. “Casting a wide net really made a world of difference, catching this quickly and getting him the right care he needed almost immediately.”

Brynn, now 4, received the genetic testing as part of a clinical trial, the results of which were recently published in the Journal of the American Medical Association. “Whole genome” tests are nearly twice as good as narrower tests at picking up genetic abnormalities that can cause disease in infants – the study found 49% of abnormalities, compared with 27% with more commonly used tests that target specific types of genetic diseases.

Genome-wide tests could solve the problem of performing more tightly targeted tests on babies, who may not yet find the disorder. Experts warn there are some problems because labs vary in how they interpret the results, and genome-wide tests are more expensive and less likely to be covered by insurance.

But researchers predict that genome-wide tests will eventually be used for millions of hospitalized babies with confusing, sometimes life-threatening conditions. In accordance with US National Human Genome Research Instituteapproximately 350 million people worldwide live with rare disorders, and approximately 80% of the more than 7,000 conditions are genetic.

“I’ve been doing clinical trials on babies for over 40 years,” said study author Dr. Jon Davis, chief of neonatal medicine at Tufts Medical Center in Boston. “It’s not often that you get to do something that you feel is really going to change the world and change clinical practice for everybody.”

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The night after Brynn was born, her mother Lindsay noticed that her skin was gray and her breathing was labored. Blood pooled under Brynn’s scalp, causing two bumps on her head.

Doctors transferred her to the neonatal intensive care unit at Cincinnati Children’s Hospital Medical Center, where she received blood transfusions and tests for various bleeding problems. She got better and went home – only to end up back in the hospital when she was about a month old for massive brain bleeding. A doctor warned that he probably wouldn’t make it. A pastor prayed with the family.

After her surgery, Brynn stayed in the NICU for two months. At various times, doctors thought he might have a vascular problem or a mass in his liver.

“Everybody was very anxious because nobody knew what the hell was going on,” Lindsay Schulte recalls. “I don’t think I slept. I mean, seeing your child almost die in front of your eyes twice is a memory I’ll never erase.”

Then the Schultes learned about the clinical trial, which involved 400 hospitalized infants. Brynn and both parents had whole genome testing. The diagnosis came in less than a week: He had a rare bleeding disorder that affects about 1 in 2 million to 1 in 3 million live births and another condition that causes a severe reaction to certain anesthetic drugs.

Doctors said the diagnosis would likely have been delayed – or even missed – with more narrower tests.

Many children in the study had genetic variants that narrower tests simply could not detect, said Dr. Jill Maron, study author and chief of pediatrics at Women and Infants Hospital of Rhode Island.

That’s because targeted tests cover maybe 1,700 of 20,000 genes, so whole-genome testing simply “picks up more stuff,” said Dr. Paul Kruszka of GeneDx, a company that offers whole-genome testing, but it hasn’t been involved in the study.

Another child in the clinical trial, Cash Denaro, 2, of Oceanside, Calif., was found to have a genetic condition called Noonan syndrome, which involves heart defects, developmental delays and other problems. His mother, Amanda Denaro, said that with the diagnosis, “we know what they think he might be delayed by, so we can work on those more — not just push it under the rug.”

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Wider access to full-genome testing is needed if more children are to be helped, experts like Maron said. Whole genome tests generally cost three times as much as narrower tests, she said, and are not covered by Medicaid in most states.

Then there’s the problem of interpreting the test results: More than 40 percent of the time in the study, the labs found the same genetic variant, but one thought it caused the disease, while the other thought it was insignificant. Philip Brooks of the National Institutes of Health, which helped pay for the research, said it “remains a topic that needs to be addressed.”

One reason for the different interpretations is that science is moving so quickly linking genes to disorders, and there is no…

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