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The role of genetic testing in small for gestational age infants

Journal of Perinatology volume 45, pages 1183–1190 (2025)Cite this article

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Abstract

Small for gestational age (SGA) infants face increased morbidity, mortality, and long-term health risks, yet causes of SGA remain unclear. While placental insufficiency and environmental factors contribute, genetic disorders play a significant role. Syndromes like Silver-Russell and Noonan are linked to SGA, but the overall genetic contribution remains uncertain. We reviewed literature on genomic sequencing in SGA and fetal growth restriction (which often precedes SGA) and identified 161 single-gene disorders. The top ten genes explained one-third of cases, but half were attributable to unique genes. Genetic disorders were frequently accompanied by congenital anomalies (often skeletal dysplasia) and developmental delays. Current guidelines for genetic evaluation of SGA are limited. Our findings support consideration of exome or genome sequencing, particularly in the setting of congenital anomalies or developmental delays. Early identification of genetic disorders can enable tailored therapy. Given the complexity of the SGA genetic landscape, prospective genomic studies are urgently needed.

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Fig. 1: Literature review to identify single gene disorders underlying small for gestational age birth.
Fig. 2: Genes found in human cases of SGA or FGR.

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Acknowledgements

This work was supported by a Precision Medicine Pilot Grant from the Irving Institute (CB, TH), and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD113827 to TH).

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  1. These authors contributed equally: Eric Kalimi, Emily Zhao.

Authors and Affiliations

  1. Harvard University, Cambridge, MA, USA

    Eric Kalimi

  2. Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Emily Zhao

  3. Division of Endocrinology, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA

    Brittany Wise-Oringer

  4. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA

    Ronald J. Wapner & Caitlin Baptiste

  5. Divisions of Reproductive Genetics and Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA

    Lorraine Dugoff

  6. Department of Statistics, Middlebury College, Middlebury, VT, USA

    Alex Lyford

  7. Division of Neonatology, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA

    Thomas Hays

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Contributions

EK and EZ conducted the literature review and data analysis and wrote the manuscript. BWO contributed to the manuscript sections regarding endocrinology. RJW, LD, and CB contributed to the manuscript sections regarding maternal-fetal medicine and clinical genetics. AL contributed to the data and statistical analyses. TH supervised and assisted in the literature review and data analysis and contributed to the manuscript. All authors were involved in preparing the final draft and approved it for publication.

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Correspondence to Thomas Hays.

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Kalimi, E., Zhao, E., Wise-Oringer, B. et al. The role of genetic testing in small for gestational age infants. J Perinatol 45, 1183–1190 (2025). https://doi.org/10.1038/s41372-025-02343-9

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