The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies
Introduction
With the advent of modern genetic methods including microarray techniques allowing genome-wide detection of microdeletions and duplications, as well as targeted gene sequencing and whole exome sequencing, there has been a much better understanding and improved identification of the etiologies of specific epileptic encephalopathies (EEs). The International League Against Epilepsy defines EEs as conditions “in which the epileptiform abnormalities are believed to contribute to progressive disturbance in cerebral function.”1 In this article, the various encephalopathies that are reviewed are presented according to age of onset of symptoms starting with the infantile EEs, and followed by the childhood EEs. As will be evident in our following review, currently, workup of such encephalopathies includes ruling out structural and metabolic disorders as well as often epilepsy gene sequencing panels and even whole exome sequencing.2
Section snippets
EIEE or Ohtahara Syndrome
Early Infantile EE (EIEE) or Ohtahara syndrome (OS) is a severe early epileptic encephalopathy. It presents within the first 3 months of life, and may occur as early as the first hour after delivery, or even in utero. The most common seizures in this syndrome are tonic, but other types can also occur, including focal and myoclonic seizures. It is a rare disorder.3 OS may evolve into West syndrome and, later, into Lennox-Gastaut syndrome (LGS). The prognosis is poor, with severe psychomotor
Landau-Kleffner Syndrome
Landau-Kleffner syndrome (LKS) is an epilepsy syndrome of middle childhood.34 It affects otherwise normally developing children between 3 and 7 years of age. Boys are twice as affected as girls. It is also referred to as acquired epileptic aphasia.
The key clinical feature of LKS is the presence of either gradual or sudden inability to understand (verbal auditory agnosia) and to use spoken language. Families often think that the child developed hearing loss, which, of course, is not the case in
Conclusions
The genetic EEs are severe brain disorders of infancy or early childhood, that are characterized by typical EEG features and intractable seizures. They result in most of the cases in significant cognitive, behavioral, and neurologic deficits. The advent of microarray techniques allowing genome-wide detection of microdeletions and duplications, as well as of targeted gene and whole exome sequencing, has allowed for a much better understanding and improved identification of the underlying genetic
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Cited by (22)
Modeling epileptic spasms during infancy: Are we heading for the treatment yet?
2020, Pharmacology and TherapeuticsCitation Excerpt :For functional classification of many of those genes and respective references, see Table 3. However, there are likely many more genes associated with epileptic spasms during infancy (D'Alonzo, Rigante, Mencaroni, & Esposito, 2018; Pavone et al., 2014; Shbarou & Mikati, 2016; Wang et al., 2019) and the pool of these genes increases constantly (Hengel et al., 2020). Multiple chromosomal abnormalities may also lead to the phenotype of spasms.
Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy
2020, Brain and DevelopmentCitation Excerpt :DEEs are intractable to various antiepileptic drugs (AEDs) and often exhibit characteristic interictal epileptiform discharges on electroencephalography (EEG), with clinical seizures appearing usually before 3 years of age. Most importantly, early infantile epileptic encephalopathy (EIEE), early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures (EIMFS), and West syndrome represent the typical early onset epileptic encephalopathies that may occur within months after birth [2,3]. In the past, seizure onset, EEG findings, and neurological features were assessed to diagnose epileptic encephalopathies.
Epilepsy genetics-considerations for clinical practice today and for the future
2020, Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Volume 2Diagnosis of seizures and encephalopathy using conventional EEG and amplitude integrated EEG
2019, Handbook of Clinical NeurologyCitation Excerpt :The similarities and differences between the syndromes are discussed by Beal et al. (2012). Further epileptic encephalopathies presenting typically in the infantile rather than the neonatal period, including epilepsy of infancy with migrating focal seizures, West syndrome, and Dravet syndrome, are not discussed further here but are reviewed by Shbarou and Mikati (2016). Several factors may influence the aEEG and cEEG other than the underlying pathology and should be considered when making any diagnosis in neonates.
Re-appraisal of callosotomy: rates and predictors of short-term seizure outcome in pediatric epileptic encephalopathy
2023, Egyptian Journal of Neurology, Psychiatry and Neurosurgery