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

Abstract

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.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…The molecular basis of epilepsy involves intricate mechanisms influencing neuronal function and excitability. Ion channel dysfunction is a prominent factor, characterized by mutations in genes encoding voltage-gated sodium channels (e.g., SCN1A, SCN2A), potassium channels (e.g., KCNQ2, KCNQ3), and calcium channels (e.g., CACNA1A), which disrupts normal neuronal excitability thresholds and propagation [ 89 , 90 ]. Furthermore, dysregulation of gamma-aminobutyric acid (GABA) signaling and glutamatergic signaling significantly impacts the balance between excitatory and inhibitory neurotransmission [ 91 ].…”