Whole genome sequencing: Screening and diagnosis

Paul Kruszka, MD, MPH, FACMG, chief medical officer of GeneDx and clinical geneticist at Children’s National Hospital, discussed the role of genetic testing in pediatric care.

“[If] a general pediatrician is seeing a child with a congenital anomaly, global developmental delay, intellectual disability, epilepsyreally, those are children that need genetic testing,” Kruszka explained. He emphasized that exome and genome sequencing are now recommended as first-tier tests for these conditions, as established by the American College of Medical Genetics in 2021. Additionally, “The American Epilepsy Society has endorsed guidelines for exome or genome for any individual of any age with unexplained epilepsy.”

Rapid genome sequencing is also becoming a key diagnostic tool in neonatal intensive care units (NICUs). “Critically ill children in an ICU environment should be also getting rapid testing,” Kruszka noted, pointing to a growing body of evidence supporting this approach. He stressed that these tests offer high diagnostic yields, stating, “Professional guidelines support it. And most important, the payers are paying for it.”

Kruszka acknowledged the challenges of payer coverage but highlighted progress in accessibility. “Most of what we do at my company at GeneDx is public payers, is Medicaid, state Medicaid programs. I think roughly 40% of children in the US have Medicaid insurance,” he explained. Over half of GeneDx’s testing is supported by Medicaid, marking significant advancement in making genetic testing available to more families.

The impact of genetic diagnoses extends beyond the clinical realm, profoundly affecting families, Kruszka has found.

“Once you make that diagnosis, that changes everything for the family,” Kruszka said. “[If nothing else], the parents stop feeling guilty."

Kruszka highlighted the importance of patient advocacy groups in supporting families and disseminating information about rare conditions. “Usually…a patient who has a diagnosis, who’s done their own research, who’s a member of patient advocacy groups, will know more about the disease than most providers or physicians,” he said.

Ultimately, genetic testing not only ends the “diagnostic odyssey” for families but also equips them with critical resources and community support, enhancing the quality of pediatric care, according to Kruszka.

Paul Kruszka, MD, MPH, FACMG, has the following disclosures:

Employment - Chief medical officer at GeneDx

In a separate video interview, Kruszka provided further background of whole genome sequencing in primary care. Click here to watch.