Genomic Sequencing Can Rapidly Diagnose Infants with Hypotonia
Article Summary
- A study led by the Miller School’s Dr. Pankaj Agrawal shows exome/genome sequencing can rapidly identify the underlying causes for neonatal hypotonia.
- Babies with hypotonia need to be diagnosed quickly to avoid the worst outcomes, but the disease can be caused by many conditions.
- Dr. Agrawal and team achieved an excellent 60% diagnosis rate for the 121 study participants.
A large, international study published in the journal Neurology has shown that genomic sequencing (exome or genome sequencing) can rapidly identify the underlying causes for neonatal hypotonia. These findings could help medical teams quickly diagnose infants and provide the most effective therapies.
“Babies with hypotonia need to be diagnosed quickly,” said Pankaj Agrawal, M.D., chief of the Division of Neonatology at the University of Miami Miller School of Medicine and Jackson Health System and senior author on the paper. “Hypotonia can be caused by many different conditions and that can lead to a long, diagnostic odyssey, where babies receive test after test and nobody is certain about the cause. Meanwhile, these infants continue to stay in the NICU while families wait for answers so that appropriate therapies can be initiated. With genomic sequencing, we can cut to the chase.”
About Hypotonia
Hypotonia is not a disease but a symptom – poor muscle tone. As a result, newborns feel “floppy” when they are being held. This can indicate one of many serious health conditions, including myopathies, muscular dystrophies, myotonic dystrophies, neuropathy and myasthenia gravis, among others.
To effectively treat patients, clinicians must rapidly determine the precise disease that’s affecting them. In some cases, rapid diagnosis and treatment can help avert the most serious health consequences.
In the past, hospitals have conducted an extensive series of tests but only limited genetic testing, which often did not identify the underlying issue. In addition, these serial tests take time sick infants cannot spare.
Genomic Sequencing for Rapid Diagnosis
Dr. Agrawal and colleagues have spent several years investigating whether comprehensive genomic sequencing could rapidly diagnose these babies. In a literature review published in JAMA Neurology in 2022, the research team showed that whole genome and whole exome sequencing could identify the underlying genetic anomaly behind hypotonia. In some cases, it pointed doctors to potential treatments.
The current study is the largest genomic study of hypotonic babies. Conducted in five premier hospitals in the U.S., U.K, Canada and Australia, study researchers sequenced 121 babies with unexplained hypotonia, many of them only days old. They diagnosed 72.
“The 60% diagnostic rate is huge,” said Dr. Agrawal. “It tells us that this is the right approach to start with and that most cases can be diagnosed without additional testing.”
While these results are promising, the research team will continue to study how genomic sequencing can improve care for hypotonic babies.
“This was powerful study, but we still have a lot more to learn,” said Dr. Agrawal. “Ultimately, we need to make the evidence so foolproof that no hospital would ever use any method other than genome sequencing to determine a baby’s underlying condition responsible for hypotonia.”
Tags: Division of Neonatology, Dr. Pankaj Agrawal, neonatology, pediatrics, rare diseases