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Case Reports
. 2025 Aug;45(9):1196-1199.
doi: 10.1002/pd.6851. Epub 2025 Jul 6.

The Prenatal Neuro-Radiological Phenotype Associated With a Recurrent Pathogenic Variant in PPP2R1A

Calder Hamill  1   2 , Stacy Goergen  3   4 , Michael Fahey  1   2   5 , Tony Roscioli  6 , Anita Gorrie  1   2 , Helen Curd  1   2 , Nikki Gelfand  1
Affiliations
Case Reports

The Prenatal Neuro-Radiological Phenotype Associated With a Recurrent Pathogenic Variant in PPP2R1A

Calder Hamill et al. Prenat Diagn. 2025 Aug.

Abstract

Background: PPP2R1A-related neurodevelopmental disorder (PPP2R1A-rNDD) is a rare condition marked by developmental delay, intellectual disability, and characteristic brain imaging findings that can be detected on prenatal neuroimaging.

Case presentation: We report three fetuses, all with a recurrent pathogenic PPP2R1A variant (c.544C〉T, p.Arg182Trp), identified at a single fetal diagnostic service over 12 months. The neuroradiological phenotype included corpus callosum dysgenesis, widening of the interhemispheric fissure and ventriculomegaly consistent with an aqueduct stenosis pattern. Two pregnancies ended in termination; one continued, with diagnosis confirmed postnatally.

Discussion: These cases broaden the prenatal neuroradiological spectrum of PPP2R1A-rNDD and, more specifically, a missense variant associated with the p.Arg182Trp change. These cases share reduced CC length (sometimes markedly) and widening of the interhemispheric fissure as common features.

Keywords: PPP2R1A; corpus callosum anomalies; pons hypoplasia; prenatal diagnosis; ventriculomegaly.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Fetal magnetic resonance imaging (MRI) findings.
See this image and copyright information in PMC

References

    1. Fath B., Bulas D., and Lee W., Fundamental and Advanced Fetal Imaging Ultrasound and MRI, 1st ed. (Wolters Kluwer, 2015).
    1. Houge G., Haesen D., Vissers L., et al., “B56δ‐Related Protein Phosphatase 2A Dysfunction Identified in Patients With Intellectual Disability,” Journal of Clinical Investigation 125, no. 8 (2015): 3051–3062, 10.1172/JCI79860. - DOI - PMC - PubMed
    1. Wallace A., Caruso P., and Karaa A., “A Newborn With Severe Ventriculomegaly: Expanding the PPP2R1A Gene Mutation Phenotype,” Journal of Paediatric Genetics 8, no. 4 (2019): 240–243, 10.1055/s-0039-1692414. - DOI - PMC - PubMed
    1. Lenaerts L., Reynhout S., Verbinnen I., et al., “The Broad Phenotypic Spectrum of PPP2R1A‐Related Neurodevelopmental Disorders Correlates With the Degree of Biochemical Dysfunction,” Genetics in Medicine 23, no. 2 (2021): 352–362, 10.1038/s41436-020-00981-2. - DOI - PMC - PubMed
    1. Douzgou S., Janssens V., and Houge G., “PPP2R1A‐Related Neurodevelopmental Disorder. 2022 May 12,” in GeneReviews® [Internet], Adam M. P., Feldman J., Mirzaa G. M., et al. (Eds), (University of Washington, Seattle, 1993–2025), https://www.ncbi.nlm.nih.gov/books/NBK580243/. - PubMed

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