The Hidden Genetic Conditions in ICU Patients
A woman in her early 20s experienced heart failure after giving birth for the first time. She recovered and had a second child a few years later, only to be discharged from the hospital with her newborn. However, within months, she was back in the hospital again, this time in heart failure, and ultimately passed away in an intensive care unit at Penn Medicine.
This tragic case is one of many that have led to a groundbreaking study published in The American Journal of Human Genetics. The research revealed that one in four adult patients admitted to intensive care units across the Penn health system had a genetic condition linked to their medical issues. Shockingly, half of these conditions were unknown at the time of admission.
Dr. Theodore Drivas, a medical geneticist at the Hospital of the University of Pennsylvania and the senior author of the study, was surprised by the scale of the findings. “I thought it would be a concerning number, but this was larger than even I thought it was going to be,” he said.
The study also uncovered significant racial disparities in the detection of genetic conditions. Sixty-three percent of white patients knew about their condition, compared to only 22.7% of Black patients. This disparity was based on a sample of 365 patients aged 18 to 40 who had participated in the Penn Medicine BioBank, a repository for health-related data used for research.
The Role of Genetic Testing
When the researchers sequenced the genome of the woman who died after childbirth, they discovered a mutation in a gene called Titin, which is known to increase the risk of heart failure in women during and after pregnancy. If doctors had been aware of this condition, they could have monitored her heart function more closely after her second delivery instead of discharging her.
Another patient in the study had multiple aneurysms following surgery, which could have been prevented if she had been screened for her genetic condition. While most patients in the study survived their ICU stay, many could have received more targeted care if their conditions had been identified earlier.
Three-quarters of the disorders found in the study had standard medical management recommendations available. However, the study did not identify individual patients, including the woman whose death was cited as an example. It remains unclear whether early diagnosis could have improved outcomes for these patients.
A Call for Universal Genetic Testing
Drivas emphasized that genetic testing is rarely offered to adults, even when they are critically ill. He sees the study as a call to action for ICU doctors to implement universal genetic testing for all adults. “We need to switch to a model where the default is to send [patients for] genetic testing, not the exception,” he said.
For decades, the medical field has assumed that older individuals are less likely to have genetic disorders. This assumption stems from the fact that many genetic diseases appear in childhood, leading doctors to focus on pediatric-onset conditions rather than those that manifest later in life.
However, Drivas pointed out that most of the diseases found in his study only cause symptoms in adulthood and may affect just one organ. This bias is also reflected in the workforce, with most medical geneticists trained to work with children, not adults.
Commonly Missed Genetic Conditions
The genetic conditions most commonly found in the study included cystic fibrosis and Marfan syndrome, both of which tended to already be diagnosed. However, other conditions, such as cardiomyopathies and those that increase the risk of aneurysms, were frequently missed.
One woman in her 30s was admitted to the ICU with multiple brain aneurysms and underwent surgery. Unfortunately, the procedure caused more aneurysms to develop at the sites where doctors had accessed her arteries. This was characteristic of vascular Ehlers-Danlos syndrome, a condition caused by mutations in the COL3A1 gene. However, she had never been offered genetic testing.
When Drivas sequenced her genome, he confirmed the mutation. Had they known, they could have warned doctors not to perform that particular procedure. “We would have said, ‘Hey, stop touching her arteries. They’re really fragile,’” he said.
The Future of Genetic Testing
Most of the patients included in the study had their first ICU visit within the past 10 years. The researchers hope to eventually return these testing results to the patients so they can receive more informed care going forward.
Drivas is unsure why the racial disparity in diagnoses is so high, but he believes the solution lies in implementing universal testing in ICUs. A study from the University of Washington showed that Black children were much less likely to get genetic diagnoses than their white counterparts. However, when genetic testing became the default in the neonatal ICU, the disparity disappeared completely.
Genetic testing is now more feasible than ever, thanks to lower costs and faster processes. For example, if someone presents with heart failure, doctors could order a targeted gene panel that should cost no more than $250 and, for most patients, be covered by insurance.
“Price has gone down, the reliability of testing has gone way up, and so it just makes it, in my opinion, kind of a no-brainer to get this done,” Drivas said.
