Docs Urged to Use Genome Tests to Diagnose Kids Early

Clinicians should prioritize genetic testing for young children who show signs of intellectual disability (ID) or developmental delays, according to a new report from the American Academy of Pediatrics (AAP), a move intended to improve care and outcomes for families.

The clinical report, published in Pediatrics, recommends genome or exome sequencing be used as first-line diagnostic tests in most cases. Chromosome microarray analysis, which looks for genetic differences at a larger scale, is also endorsed as a complementary approach. Together, these tools can identify a wide range of genetic conditions, many of which would otherwise go undiagnosed or be discovered only after years of inconclusive, nongenetic testing.

“Genetic testing is no longer something that should be considered a last resort,” said Joan Stoler, MD, a clinical geneticist at Boston Children’s Hospital, Boston, and an author of the report. “These tests provide real answers that can directly impact the care and support children and families receive.”

Pediatricians As Frontline Navigators

Neurodevelopmental disorders — including global developmental delay and ID — affect about 1 in 6 children in the US. But diagnosing these conditions often takes years. The new report aims to speed up that process and ensure clinicians consider comprehensive testing earlier.

Genomic testing can influence medical decisions in a significant number of cases, said Tomi Pastinen, MD, PhD, director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City in Kansas City, Missouri, who was not involved with the report.

“That could be family planning guidance or actual medical management of the child,” Pastinen said.

The new guidance equips pediatricians, often the first point of contact for concerned parents, with a clearer framework for initiating testing, he said.

The AAP identified two paths to diagnosis. First, a phenotype-driven route for children with specific physical or behavioral signs of a known condition. The other is considered “hypothesis-free,” or an agnostic process to use when symptoms are less specific.

Stoler said the agnostic approach is appropriate “if no specific disorder is suspected based on the signs, symptoms, and physical examination.”

Children older than 6 months with global developmental delay, ID, or developmental regression suspected to have a genetic basis should be tested.

Exome or genome sequencing is recommended as a first-line diagnostic tool, ideally performed on the child and both biological parents. Chromosomal microarray testing may also be ordered as a complementary first-tier test as it is useful for detecting changes in the number of copies of sections of DNA, the report stated.

If initial testing does not yield a diagnosis, clinicians can consider fragile x testing, single-gene or panel testing as second-line testing, the report outlined. Inborn errors of metabolism screening is recommended if newborn screening is abnormal.

The report also suggests potentially testing family members if a pathogenic variant is found.

More Than a Diagnosis 

Scott Demarest, MD, a pediatric neurologist and medical director of the Precision Medicine Institute in Aurora, Colorado, said that in his facility, as many as half of children who undergo genetic testing receive a diagnosis for their developmental challenges. In his experience with pediatric epilepsy, a diagnosis changed the prescribed medication more than 25% of the time.

While many patients do receive treatment, a diagnosis also “helps us avoid unnecessary testing, allows us to monitor for other condition-specific complications, and can guide treatment,” Demarest said.

Even when no treatment is available, a diagnosis can help clinicians identify related health conditions and inform a child’s reproductive decisions later in life, the report noted.

“Conditions associated with the developmental delay will not be clear before you know the molecular cause,” Pastinen said. “It has a lot of ramifications in knowing what the cause is, even if there’s no specific treatment.”

According to the report, up to 50% of cases of global developmental delay or ID may stem from underlying genetic conditions. Identifying the cause early allows families to monitor for related health concerns and connect with condition-specific support groups and services.

“Knowing what’s going on at the genetic level can make a huge difference,” Stoler said. “It’s about clarity, not just for doctors, but for families navigating an uncertain journey.”

Access and Adoption Challenges Remain

Pediatricians are generally willing to refer or order genetic testing but face several barriers, said Julian Martinez-Agosto, MD, PhD, an associate professor of genetics at UCLA Health.

“Perceptions about lack of clinical utility or impact on patient outcomes have been a primary barrier,” said Martinez-Agosto, who was not involved with the AAP report. “Other barriers include lack of time due to high clinic volumes, unfamiliarity with the testing process, and insecurity about discussing results — especially when they’re uncertain or relate to reproductive planning.”

Martinez-Agosto said health systems can improve access by offering primary care clinicians accessible education and tools to support counseling and interpretation.

Still, interpreting genetic results can be complex. Some findings may present unclear significance. Others may uncover unrelated but medically relevant information, such as a predisposition to adult-onset diseases.

“It would be optimal for the pediatrician to have the involvement of a trained genetic professional,” Stoler said.

Indeed, the report states that genetic counseling should be offered both before and after testing, especially when test results carry uncertain significance or broader family implications.

Additional barriers include cost and inconsistent insurance coverage. However, Pastinen noted recent signs of improvement.

“In the last 3 years, there’s been a substantial increase in Medicaid coverage for early genomic sequencing in unsolved pediatric disease,” Pastinen said

He also said the new AAP guidance could help push insurance companies still hesitant to cover these tests.

“Every year we see better coverage by insurers,” he said. “I hope this is another piece in the reimbursement puzzle.”

Demarest had consulted for, received grant funding from, and served on advisory boards of BioMarin, Neurogene, and Marinus, among others. The Precision Medicine Institute at Children’s Hospital Colorado has ongoing partnerships with Illumina, although Demarest reported not receiving any direct compensation from this partnership. Stoler, Pastinen, and Martinez-Agosto reported no relevant financial conflicts of interest.

Lara Salahi is a health journalist based in Boston.