From diagnosis to treatment in genetic epilepsies: Implementation of precision medicine in real-world clinical practice

De Wachter, Matthias; Schoonjans, An-Sofie; Weckhuysen, Sarah; Van Schil, Kristof; Löfgren, Ann; Meuwissen, Marije; Jansen, Anna; Ceulemans, Berten

doi:10.1016/j.ejpn.2023.11.003

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Although our study design included patients with epilepsy onset within 36 months of age, the mean age of onset is significantly lower (11 months), reflecting previous literature data [24][25][26] and the decline of diagnostic yield of genetic testing with increasing age at epilepsy onset [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

Cavirani,

Spagnoli,

Caraffi

et al. 2024

IJMS

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The genetic causes of epilepsies and developmental and epileptic encephalopathies (DEE) with onset in early childhood are increasingly recognized. Their outcomes vary from benign to severe disability. In this paper, we wished to retrospectively review the clinical, genetic, EEG, neuroimaging, and outcome data of patients experiencing the onset of epilepsy in the first three years of life, diagnosed and followed up in four Italian epilepsy centres (Epilepsy Centre of San Paolo University Hospital in Milan, Child Neurology and Psychiatry Unit of AUSL-IRCCS di Reggio Emilia, Pediatric Neurology Unit of Vittore Buzzi Children’s Hospital, Milan, and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia). We included 168 patients (104 with monogenic conditions, 45 with copy number variations (CNVs) or chromosomal abnormalities, and 19 with variants of unknown significance), who had been followed up for a mean of 14.75 years. We found a high occurrence of generalized seizures at onset, drug resistance, abnormal neurological examination, global developmental delay and intellectual disability, and behavioural and psychiatric comorbidities. We also documented differing presentations between monogenic issues versus CNVs and chromosomal conditions, as well as atypical/rare phenotypes. Genetic early-childhood-onset epilepsies and DEE show a very wide phenotypic and genotypic spectrum, with a high risk of complex neurological and neuropsychiatric phenotypes.

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Section: Discussionmentioning

confidence: 99%

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

Cavirani,

Spagnoli,

Caraffi

et al. 2024

IJMS

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The promise of personalized medicine in pediatric epilepsy – The time has come

Pearl

2024

European Journal of Paediatric Neurology

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Antecedent Neonatal Hypoglycaemic Brain Injury, commonest cause of Early-Childhood Epilepsy in Indian Children

Gupta,

Narang,

et al. 2024

Preprint

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Paediatric epilepsies have diverse etiologies from structural brain lesions to monogenic disorders. Prospective studies from low-middle income countries which had used modern diagnostic methods like 3-T MRI and genetic testing for underlying causes in early-childhood epilepsies, are lacking. Similarly, data on long-term epilepsy outcomes is also not available. In this prospective study, consecutive patients with onset of epilepsy till five years of age were enrolled. Following detailed clinical phenotyping and after ruling out a structural-acquired cause on 3T-MRI, sequential genetic testing with Exome sequencing (ES) as a trio and if required Chromosomal Microarray (CMA)/Multiplex ligand PCR assay (MLPA) were performed. After this evaluation, patients were classified into International League Against Epilepsy (ILAE) defined etiological groups. Phenotypic differences between acquired and congenital causes were also evaluated. Epilepsy outcome at 24 months follow-up was ascertained. Two hundred and thirty-one children were recruited over 12 months. The underlying etiology could be confirmed in 176 (76%) patients. The structural group (54%) was the commonest, followed by genetic (19.5%), metabolic (2%), Unknown (19%) and incompletely investigated (5%: Normal MRI, genetic evaluation not consented). Neonatal Hypoglycaemic Brain Injury (NHBI) was the most common single cause (50; 22%). The broad aetiological groups included acquired causes in 47% and congenital causes in 53%. In the acquired cohort, the predominant initial seizure type was a focal seizure (P = 0.01) or an Infantile Spasm (P < 0.001), while generalized seizures were more frequent in the congenital group (P < 0.001). Patients with an acquired cause were more likely to have IUGR, developmental delay, cortical visual impairment, and hypertonia (all P < 0.001). MRI helped confirm the underlying cause in 126 (54.5%) of the patients. A molecular diagnosis was achieved in 61 (54%) of 113 tested. ES as a trio was diagnostic in 50%, while CMA was 3%. Mutation positivity was more likely with seizure onset in infancy, developmental delay or presence of hypotonia (all P < 0.001), or Developmental and Epileptic Encephalopathy (P = 0.01). A total of 57 of 207 (28%) patients at 24 months follow-up had drug-resistant epilepsy (DRE). On multivariate regression, only the younger age of seizure onset (P = .027) and developmental delay (P = .025) were associated with DRE. In this comprehensive prospective study of Indian children with early childhood epilepsy, using cutting-edge technology, we could confirm an underlying etiology in a majority of our patients. NHBI, a preventable condition was the commonest underlying cause. It is pertinent, that in India, guidelines on correct postnatal feeding practices are formulated urgently.

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From diagnosis to treatment in genetic epilepsies: Implementation of precision medicine in real-world clinical practice

Cited by 4 publications

References 57 publications

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

The promise of personalized medicine in pediatric epilepsy – The time has come

Antecedent Neonatal Hypoglycaemic Brain Injury, commonest cause of Early-Childhood Epilepsy in Indian Children

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