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Profiling the developmental signatures of genetic global developmental delay

Pediatric Research volume 98, pages 1625–1626 (2025)Cite this article

The Original Article was published on 30 April 2025

Global developmental delay (GDD) affects approximately 3% of children under five years of age and is characterized by significant delays in two or more developmental domains, including gross and fine motor skills, speech/language, cognition, and/or social/emotional development.1 A study published in this issue of Pediatric Research by Shan and colleagues2 provides valuable insights into the clinical distinctions between genetic and non-genetic forms of GDD, a critical step toward more personalized diagnostic and therapeutic approaches for affected children and improving counseling for their families.

This current study contributes to our understanding of the genomic etiologies of GDD, now possible through the use of broad genetic testing. While brain injury3,4 and environmental5,6 exposures may contribute to the development of GDD, multiple studies demonstrate that genomic differences are a major cause of or contribute to GDD.7,8,9 Studies using exome and genome sequencing for GDD have reported diagnostic yields of approximately 30–40%8,9,10, a marked increase from approximately 15% reported with chromosomal microarray alone.11,12,13 Given this, the American College of Medical Genetics and Genomics now recommends exome or genome sequencing (ES/GS) as first- or second-line tests for children with GDD.10 Genome sequencing permits analysis for single-nucleotide variants (SNVs) as well as copy number variants (CNVs), both of which may cause GDD but may be missed with older techniques, with recent studies reporting diagnostic yields for GS of up to 61% for early childhood GDD.7,13,14

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  1. Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri, USA

    Marina Metzler, Zachary A. Vesoulis & Jennifer A. Wambach

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  1. Marina Metzler
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  2. Zachary A. Vesoulis
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Correspondence to Zachary A. Vesoulis.

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Metzler, M., Vesoulis, Z.A. & Wambach, J.A. Profiling the developmental signatures of genetic global developmental delay. Pediatr Res 98, 1625–1626 (2025). https://doi.org/10.1038/s41390-025-04268-7

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