Genomic Medicine Speeds Neonatal Diagnosis and Disease Identification

Genomic sequencing has the potential to diagnose rare genetic diseases in newborns. But these technologies have yet to be widely adopted, limiting access to care.

In a review published in the European Journal of Human Genetics, a Nature journal, neonatologists at the University of Miami Miller School of Medicine, Holtz Children’s Hospital of Jackson Health System, Harvard Medical School and Boston Children’s Hospital examined the current neonatal sequencing landscape to see how it can be improved.

“I’m a neonatologist, and I’ve seen firsthand how valuable this technology can be,” said study senior author Pankaj Agrawal, M.D., chief of the Division of Neonatology in the Miller School Department of Pediatrics and Jackson Health System. “Sequencing provides comprehensive results, making it an excellent first-line diagnostic for babies who may have an underlying genetic condition.”

Genomic Sequencing Guides Clinical Treatment

Whole genome and whole exome (which only reads protein-producing genes) sequencing can provide fast answers to treat sick newborns. In recent years, rapid whole genome sequencing (rWGS) has provided results in days or even hours, in many cases guiding treatment.

Genomic sequencing can help decipher genetic diseases that share traits and don’t fully manifest in the first weeks or months of life. It saves time and money by accelerating diagnoses, reducing hospital stays and eliminating unnecessary tests and procedures. One study led by Dr. Agrawal showed sequencing changed clinical management in 64% of NICU babies.

“Genomics can be helpful for neonates on so many levels,” said Dr. Agrawal. “It gives us a precise screening tool to catch genetic variants and intervene quickly. Now that the cost of sequencing has come way down, it should be routine in every NICU.”

Dr. Agrawal is inspired by a case in which a baby suffered from an unknown condition. Genomic sequencing showed the child had a mutation for a seizure disorder. Identifying the mutation gave the parents critical information to use pre-implantation genetic diagnostics to later have two healthy babies.

Improving Access to Genomic Sequencing

Most NICU babies don’t have immediate access to sequencing. Neonatologists often rely on specific diagnostics that test a small subset of genes or only look at chromosomal abnormalities. Sometimes, after the tests come back negative, the child can be referred for sequencing. This approach, argue the authors, wastes valuable time while diseases progress.

The study explores different barriers to access. In some cases, clinicians are simply reluctant to adopt sequencing. In others, insurance approvals can be an issue. Perhaps the most significant barrier is a shortage of geneticists and genetic counselors, an issue in community hospitals.

In response, Dr. Agrawal and colleagues created the Virtual Genome Center for Infant Health (VIGOR). This NIH-funded project uses telehealth to support under-resourced NICUs in Massachusetts, New Jersey, Texas and now Miami, with ongoing discussions to add NICUs in Alabama and Mississippi.

The next step is to develop more and better treatments. There are thousands of rare genetic disorders but only hundreds of corresponding therapies. Dr. Agrawal and colleagues are working with life sciences companies and other institutions to identify new approaches.

“In some cases, there are gene therapies that could help,” said Dr. Agrawal. “In others, we can custom design an antisense oligonucleotide therapy, which can block RNA products of disease-causing genes for that specific variation. We can also get these kids enrolled in clinical trials, but we have to know their specific genetic variation first. That’s why genomic sequencing is so powerful. Once we know the problem, we can bring so many tools together to potentially solve it.”

Tags: Department of Pediatrics, Dr. Pankaj Agrawal, genomics