Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex
Summary: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2, leading to mTOR pathway dysregulation and a spectrum of systemic and neurological manifestations. Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder frequently a...
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425001847 |
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| author | Nicola Specchio Valentina Di Micco Mirte Scheper Eleonora Aronica Paolo Curatolo |
| author_facet | Nicola Specchio Valentina Di Micco Mirte Scheper Eleonora Aronica Paolo Curatolo |
| author_sort | Nicola Specchio |
| collection | DOAJ |
| description | Summary: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2, leading to mTOR pathway dysregulation and a spectrum of systemic and neurological manifestations. Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder frequently associated with early-onset, drug-resistant epilepsy, intellectual disability, and autism spectrum disorder—collectively known as TSC-associated developmental and epileptic encephalopathy (DEE). Advances in prenatal diagnostics and biomarker research now enable presymptomatic identification of high-risk infants. This review aims to synthesize current evidence on biomarker-informed, mechanism-based strategies for secondary prevention of DEE in TSC, offering a framework for personalized early interventions. Biomarkers, such as interictal epileptiform discharges, pathogenic TSC2 variants, and advanced neuroimaging metrics, predict epilepsy risk and neurodevelopmental trajectories. Preventive approaches include early initiation of vigabatrin and mTOR inhibitors, which show potential in reducing epilepsy severity and improving outcomes. Emerging strategies, including gene therapy, multi-omic profiling, and environmental enrichment, offer promise for disease modification. By linking predictive biomarkers to disease-modifying strategies, this review outlines a proactive and personalised approach to prevent or mitigate TSC-associated DEE. These insights help advance clinical decision-making and promote a shift toward precision prevention in paediatric epilepsy. |
| format | Article |
| id | doaj-art-e5dec2345e2e47d98369123f6f83e167 |
| institution | DOAJ |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-e5dec2345e2e47d98369123f6f83e1672025-08-20T02:58:19ZengElsevierEBioMedicine2352-39642025-06-0111610574010.1016/j.ebiom.2025.105740Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complexNicola Specchio0Valentina Di Micco1Mirte Scheper2Eleonora Aronica3Paolo Curatolo4Neurology Epilepsy and Movement Disorders Unit, Bambino Gesu’ Children’s Hospital, IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies, EpicARE, Rome, Italy; University Hospitals KU Leuven, Belgium; Corresponding author. Department of Neuroscience, Bambino Gesù Children’s Hospital, IRCCS, Piazza S. Onofrio 4, Rome 00165, Italy.Neurology Epilepsy and Movement Disorders Unit, Bambino Gesu’ Children’s Hospital, IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies, EpicARE, Rome, ItalyDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the NetherlandsDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the NetherlandsChild Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, ItalySummary: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2, leading to mTOR pathway dysregulation and a spectrum of systemic and neurological manifestations. Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder frequently associated with early-onset, drug-resistant epilepsy, intellectual disability, and autism spectrum disorder—collectively known as TSC-associated developmental and epileptic encephalopathy (DEE). Advances in prenatal diagnostics and biomarker research now enable presymptomatic identification of high-risk infants. This review aims to synthesize current evidence on biomarker-informed, mechanism-based strategies for secondary prevention of DEE in TSC, offering a framework for personalized early interventions. Biomarkers, such as interictal epileptiform discharges, pathogenic TSC2 variants, and advanced neuroimaging metrics, predict epilepsy risk and neurodevelopmental trajectories. Preventive approaches include early initiation of vigabatrin and mTOR inhibitors, which show potential in reducing epilepsy severity and improving outcomes. Emerging strategies, including gene therapy, multi-omic profiling, and environmental enrichment, offer promise for disease modification. By linking predictive biomarkers to disease-modifying strategies, this review outlines a proactive and personalised approach to prevent or mitigate TSC-associated DEE. These insights help advance clinical decision-making and promote a shift toward precision prevention in paediatric epilepsy.http://www.sciencedirect.com/science/article/pii/S2352396425001847Tuberous sclerosis complex (TSC)mTOR pathway dysregulationDevelopmental and epileptic encephalopathy (DEE)Presymptomatic interventionBiomarkers and precision medicine |
| spellingShingle | Nicola Specchio Valentina Di Micco Mirte Scheper Eleonora Aronica Paolo Curatolo Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex EBioMedicine Tuberous sclerosis complex (TSC) mTOR pathway dysregulation Developmental and epileptic encephalopathy (DEE) Presymptomatic intervention Biomarkers and precision medicine |
| title | Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| title_full | Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| title_fullStr | Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| title_full_unstemmed | Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| title_short | Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| title_sort | mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex |
| topic | Tuberous sclerosis complex (TSC) mTOR pathway dysregulation Developmental and epileptic encephalopathy (DEE) Presymptomatic intervention Biomarkers and precision medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425001847 |
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