Adult phenotypes of genetic developmental and epileptic encephalopathies DOI Creative Commons
Angeliki Vakrinou,

Susanna Pagni,

James D. Mills

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 24, 2024

Abstract Developmental and epileptic encephalopathies constitute a group of severe epilepsies, with seizure onset typically occurring in infancy or childhood, diverse clinical manifestations, including neurodevelopmental deficits multimorbidities. Many have genetic aetiologies, identified up to 50% individuals. Whilst classically considered paediatric disorders, most are compatible survival into adulthood, but their adult phenotypes remain inadequately understood. This cross-sectional study presents detailed 129 adults (age range 17–71 years), developmental involving causal variants 42 genes. We describe disease aspects, we sought insights from the age-related trends expression genes involved. Most (69.7%) presence encephalopathy correlating worse cognitive (P = 0.0007). However, phenotypic variability was observed, ranging those seizure-free individuals normal EEG intermediate phenotypes. found across individual gene trends, suggesting that other influential factors likely at play. Mobility, feeding communication impairments were common, significant dependence on others for activities daily living. Neurological psychiatric comorbidities prevalent, along additional systemic particularly musculoskeletal, cardiac gastrointestinal conditions, highlighting need comprehensive multisystemic monitoring. Despite an average diagnostic delay 25.2 years, aetiology-based therapeutic interventions feasible 54.8% cohort, underscoring critical genome-wide testing these Optimizing control remains necessary, it may not be sufficient ensure good outcomes, which differ significantly childhood metrics, like function independence Therapies addressing aspects beyond seizures necessary improving overall outcomes. Understanding intricate relationship between molecular pathways is crucial development appropriate gene-specific therapies timely intervention. prospective data also needed define complexities, such studies necessity take years acquire: can inform care strategies both populations now.

Language: Английский

Assessing the diagnostic performance of investigations in pediatric myoclonic epilepsies: A retrospective cohort study DOI Creative Commons

Séverine Brulé,

Blandine Dozières‐Puyravel,

Hala Nasser

et al.

Epilepsia, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Objective The primary purpose was to assess the diagnostic performance of investigations in children with myoclonic epilepsy. secondary objectives were examine definitive syndromic diagnoses and report outcomes pediatric epilepsies. Methods We conducted a retrospective monocentric study from center for rare included patients investigated epilepsy at our 2009 2022. Data collected their medical records. Results Forty‐one included; 32 (78%) underwent untargeted etiological investigations, including brain magnetic resonance imaging diverse laboratory tests rule out an underlying etiology progressive myoclonus (PME). These led diagnosis two patients, exclusively based on genetic investigations. At final follow‐up, established nine (22%). diverse, comprising infancy, absences, Rasmussen syndrome, PME. Some diagnosed nonsyndromic developmental epileptic encephalopathy or unclassified Developmental delay regression initial evaluation found be significantly associated unfavorable neurological outcome, total number antiseizure medications (ASMs) prescribed, unlikelihood achieving ASM freedom. No abnormal head circumference born consanguineous union favorable outcome group, although this finding did not reach statistical significance. Significance Except need promptly identify diseases which precision medicine treatments are available, first‐line approach seems reasonable investigate myoclonus.

Language: Английский

Citations

0
Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies DOI Creative Commons

Alexandra D. Medyanik,

Polina E. Anisimova,

Angelina Kustova

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 133 - 133

Published: Jan. 15, 2025

Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with seizures, severe delay or regression psychomotor development, cognitive behavioral deficits. What sets DEEs apart is their complex interplay epilepsy developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic therapeutic challenges. Intellectual disability complicates potential treatment. Pathogenic variants found in 30–50% patients DEE. Many genes mutated encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up significant proportion DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption dendrite axon growth, maintenance synapse formation abnormalities —synaptopathies. Here, we review recent publications on non-channelopathies an emphasis the linking epileptiform activity intellectual disability. We focus three major describe several recently identified involved pathogenesis

Language: Английский

Citations

0
Development and validation of a predictive model for seizure recurrence following discontinuation of antiseizure medication in children with epilepsy: a systematic review and meta-analysis, and prospective cohort study DOI Creative Commons
Ke Dai, Dan Tang, Li Bao

et al.

EClinicalMedicine, Journal Year: 2025, Volume and Issue: 82, P. 103154 - 103154

Published: March 12, 2025

Language: Английский

Citations

0
Adult phenotypes of genetic developmental and epileptic encephalopathies DOI Creative Commons
Angeliki Vakrinou,

Susanna Pagni,

James D. Mills

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 24, 2024

Abstract Developmental and epileptic encephalopathies constitute a group of severe epilepsies, with seizure onset typically occurring in infancy or childhood, diverse clinical manifestations, including neurodevelopmental deficits multimorbidities. Many have genetic aetiologies, identified up to 50% individuals. Whilst classically considered paediatric disorders, most are compatible survival into adulthood, but their adult phenotypes remain inadequately understood. This cross-sectional study presents detailed 129 adults (age range 17–71 years), developmental involving causal variants 42 genes. We describe disease aspects, we sought insights from the age-related trends expression genes involved. Most (69.7%) presence encephalopathy correlating worse cognitive (P = 0.0007). However, phenotypic variability was observed, ranging those seizure-free individuals normal EEG intermediate phenotypes. found across individual gene trends, suggesting that other influential factors likely at play. Mobility, feeding communication impairments were common, significant dependence on others for activities daily living. Neurological psychiatric comorbidities prevalent, along additional systemic particularly musculoskeletal, cardiac gastrointestinal conditions, highlighting need comprehensive multisystemic monitoring. Despite an average diagnostic delay 25.2 years, aetiology-based therapeutic interventions feasible 54.8% cohort, underscoring critical genome-wide testing these Optimizing control remains necessary, it may not be sufficient ensure good outcomes, which differ significantly childhood metrics, like function independence Therapies addressing aspects beyond seizures necessary improving overall outcomes. Understanding intricate relationship between molecular pathways is crucial development appropriate gene-specific therapies timely intervention. prospective data also needed define complexities, such studies necessity take years acquire: can inform care strategies both populations now.

Language: Английский

Citations

0