Mosaic PPP3CA Variant in a Child with Neurodevelopmental Delay Without Epilepsy

Lynn Srour¹ and Chadi AL Alam²*

¹ Doctorate in Life Science/Human Nutrition, Lead Scientist and Nutrigenetic Expert, Xcode Life Sciences, Pvt. Ltd. Chennai, India
² R&D Intern, Xcode Life Sciences, Pvt. Ltd. Chennai, India

*Corresponding Author: Chadi AL Alam, Pediatrics and Pediatric Neurology, American Center for Psychiatry and Neurology - ACPN, Abu Dhabi and Al Ain, United Arab Emirates and Haykel Hospital, El koura, Lebanon.

Received: November 11, 2025; Published: December 12, 2025

Abstract

We report a 5-year-10-month-old girl with global developmental delay, speech and behavioral difficulties, and no history of epilepsy. Genetic testing revealed a heterozygous mosaic PPP3CA variant (c.843C>G; p.His281Gln) within the catalytic domain, previously associated with Developmental and Epileptic Encephalopathy Type 91 (DEE91). Brain MRI and EEG were normal. The mosaic nature of the variant likely explains the milder, non-epileptic phenotype. This case expands the clinical spectrum of PPP3CA-related disorders and highlights the modulatory effect of mosaicism on disease severity.

Keywords: Occupational Therapy (OT); PPP3CA

References

1. Myers CT., et al. “De novo mutations in PPP3CA cause severe neurodevelopmental disease with seizures”. American Journal of Human Genetics 101 (2017): 516-524.
2. OMIM Entry #617711. Developmental and epileptic encepha- lopathy 91; DEE91 (PPP3CA).
3. EuroEPINOMICS-RES Consortium, Epilepsy Phenome/Ge- nome Project, Epi4K Consortium. “De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies”. American Journal of Human Genetics 95 (2014): 360-370.
4. Castiglioni , et al. “Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter”. Orphanet Journal of Rare Diseases 19.1 (2024): 481.
5. Wang , et al. “New variants and genotype-phenotype correla- tion of PPP3CA-related developmental and epileptic encepha- lopathy”. Frontiers in Neuroscience 19 (2025): 1570997.
6. Yang S., et al. “Clinical and Genetic Study on a Chinese Pa- tient with Infantile Onset Epileptic Encephalopathy carrying a PPP3CA Null Variant: a case report”. BMC Pediatrics 1 (2020): 315.
7. Favaro , et al. “PPP3CA gene-related developmental and epi- leptic encephalopathy: Expanding the electro-clinical pheno- type”. Seizure 121 (2024): 253-261.
8. Mizuguchi , et al. “Loss-of-function and gain-of-function mu- tations in PPP3CA cause two distinct disorders”. Human Mo- lecular Genetics 27.8 (2018): 1421-1433.

Citation

Citation: Daniyal Ahmed., et al. “Unseen Risks: The Association Between Screen Time and Refractive Errors in Ophthalmology Patients at Al-Nafees Medical College Hospital". Acta Scientific Clinical Case Reports 6.11 (2025): 01-03.

Copyright

Copyright: © 2025Daniyal Ahmed., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.