Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies
Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental d...
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MDPI AG
2025-01-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/133 |
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| author | Alexandra D. Medyanik Polina E. Anisimova Angelina O. Kustova Victor S. Tarabykin Elena V. Kondakova |
| author_facet | Alexandra D. Medyanik Polina E. Anisimova Angelina O. Kustova Victor S. Tarabykin Elena V. Kondakova |
| author_sort | Alexandra D. Medyanik |
| collection | DOAJ |
| description | Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30–50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities —synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE. |
| format | Article |
| id | doaj-art-76b666dfa4b34e9ba0cb3fef7e79890c |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-76b666dfa4b34e9ba0cb3fef7e79890c2025-01-24T13:25:19ZengMDPI AGBiomolecules2218-273X2025-01-0115113310.3390/biom15010133Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond ChannelopathiesAlexandra D. Medyanik0Polina E. Anisimova1Angelina O. Kustova2Victor S. Tarabykin3Elena V. Kondakova4Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaDevelopmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30–50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities —synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE.https://www.mdpi.com/2218-273X/15/1/133neurodevelopmental disordersdevelopmental delaymetabolic disorderssynaptopathiesmalformations of cortical developmentpathogenic variant |
| spellingShingle | Alexandra D. Medyanik Polina E. Anisimova Angelina O. Kustova Victor S. Tarabykin Elena V. Kondakova Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies Biomolecules neurodevelopmental disorders developmental delay metabolic disorders synaptopathies malformations of cortical development pathogenic variant |
| title | Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies |
| title_full | Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies |
| title_fullStr | Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies |
| title_full_unstemmed | Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies |
| title_short | Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies |
| title_sort | developmental and epileptic encephalopathy pathogenesis of intellectual disability beyond channelopathies |
| topic | neurodevelopmental disorders developmental delay metabolic disorders synaptopathies malformations of cortical development pathogenic variant |
| url | https://www.mdpi.com/2218-273X/15/1/133 |
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