The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies

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Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated.

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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