For families with children experiencing intellectual disability (ID) and developmental delay (DD), the search for answers can be particularly long and challenging. Multiple specialist visits, repeat and unnecessary testing, and months or years of uncertainty are all common parts of the diagnostic odyssey.
A recent study published in Frontiers in Neurology evaluated the clinical utility of Baylor Genetics’ Whole Genome Sequencing (WGS) in more than 650 children with ID/DD, one of the largest cohorts evaluated to date. Results showed that nearly one-third of patients received a genetic diagnosis, which indicates the benefits of genome sequencing as an early diagnostic tool for children with neurodevelopmental disorders.
Why This Matters
Neurodevelopmental disorders affect about 1-3% of children in the United States, as of 20141. Many of these are multisystem disorders, affecting both neurological function as well as multiple other organ systems. Identifying or ruling out an underlying genetic cause can provide valuable information, leading to more precise clinical management, better care planning, and improved access to support and resources.
Also, while traditional tests such as chromosomal microarray analysis (CMA), Fragile X repeat expansion analysis, and targeted panels can detect variants in specific genes or types of variants, they can also miss clinically relevant findings that support a diagnosis. Further, sequential testing approaches, even if ultimately informative, can significantly prolong the diagnostic odyssey for patients.
Genome sequencing offers a highly comprehensive view of a patient’s DNA, enabling clinicians to identify more genetic changes in a single test, potentially shortening time to diagnosis. Prior studies on the clinical utility of genome sequencing in patients with neurodevelopmental disorders reported diagnostic yields of 21-41% 2-6.
Key Findings
In this retrospective study, WGS provided:
- A genetic diagnosis for 31.1% (207/666) of all patients with ID/DD
- 35.3% (103/292) diagnostic yield in patients who had not undergone prior genetic testing
- 48.5% (63/130) diagnostic yield in patients who underwent rapid trio WGS
- 12.6% (16/127) of patients who had previously received exome sequencing received at least one new diagnosis
About 90% of positive genetic findings directly explained the patient’s ID/DD phenotype. By identifying the specific underlying genetic cause, providers may be better equipped to confirm a diagnosis, guide management decisions, and inform families about risk and future planning.
Overall, the results demonstrate that genome sequencing can uncover important findings, even when prior genetic tests, including exome sequencing, are negative or inconclusive. These findings also further strengthen the growing body of evidence that supports the benefits of genome sequencing as a first-tier testing approach for neurodevelopmental disorders7.
Detecting Variants Missed by Other Tests
Also in the study, nearly 8% of diagnoses made by WGS involved variant types that may have not been detected through exome sequencing or standalone tests.
These variants included:
- Short tandem repeat (STR) expansions
- Deep intronic variants
- Other noncoding variants
- Variants within the mitochondrial genome
- Complex structural variants
Because genome sequencing can identify clinically relevant findings beyond protein-coding regions and variant types, this test helps clinicians reach diagnoses that might otherwise remain unknown.
Delivering Earlier Answers for Families
While no single test can always lead to a diagnosis, this study further demonstrates the value of early genome sequencing.
These results also reinforce recent recommendations from medical societies such as the American College of Medical Genetics and Genomics (ACMG) and the American Academy of Pediatrics (AAP), which both supported the use of genome sequencing for children with ID/DD.
For providers, the findings highlight the importance of choosing WGS earlier in a patient’s diagnostic journey. Early genome sequencing can lead to faster diagnoses, more informed medical decisions, and better patient outcomes by potentially shortening the diagnostic odyssey. In some cases, comprehensive testing can inform targeted therapies and rare disease clinical trial enrollment.
Looking Ahead
The study also highlights how WGS can be supported by additional multimodal testing approaches. While WGS offers a highly comprehensive initial test, some unresolved cases may benefit from additional technologies that provide complementary biological insights. For example, RNA sequencing can be used to help clarify predicted splicing variants, while optical genome mapping may identify certain complex structural variants that are difficult to detect with WGS alone.
As genomic technologies advance with the inclusion of complementary multimodal approaches, providers now have even more tools to uncover genetic causes and help families move towards answers sooner.
Explore our WGS test and how it could help your patients.
Additional Resources
- Poster | Beyond Exome Sequencing: The Added Value of Genome Sequencing in Pediatric Intellectual Disability and Global Developmental Delay presented at the 2026 American Academy of Pediatrics (AAP) Conference
- Video | Genomic sequencing recommended earlier in evaluation of developmental delay with Christine Eng, MD, Chief Medical Officer and Chief Quality Officer at Baylor Genetics
- Visit our partnership page on the Child Neurology Society (CNS) website for webinars and other resources
References
- Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics . Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219
- Lee HF, Chi CS, Tsai CR. Diagnostic yield and treatment impact of whole-genome sequencing in pediatric neurological disorders. Dev Med Child Neurol. 2021;63(8):934-938. doi:10.1111/dmcn.14722
- Sanchis-Juan A, Megy K, Stephens J, et al. Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders. Am J Hum Genet. 2023;110(8):1343-1355. doi:10.1016/j.ajhg.2023.07.007
- van der Sanden BPGH, Schobers G, Corominas Galbany J, et al. The performance of genome sequencing as a first-tier test for neurodevelopmental disorders. Eur J Hum Genet. 2023;31(1):81-88. doi:10.1038/s41431-022-01185-9
- Sun Y, Peng J, Liang D, et al. Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study. Hum Mutat. 2022;43(5):568-581. doi:10.1002/humu.24347
- Lindstrand A, Ek M, Kvarnung M, et al. Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability. Genet Med. 2022;24(11):2296-2307. doi:10.1016/j.gim.2022.07.022
- Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics . Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay: Clinical Report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219
