The genetic landscape of the epileptic encephalopathies of infancy and childhood

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• 作者：Amy McTague ; MBChB^a ; ^c ; Katherine B Howell ; MBBS^d ; ^e ; ^f ; ^&dagger ; ; Prof J Helen Cross ; PhD^b ; ^c ; ^&dagger ; ; Manju A Kurian ; PhD^a ; ^c ; Prof Ingrid E Scheffer ; PhD^d ; ^e ; ^g ; ^h ; ^{scheffer@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Lancet Neurology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：15
• 期：3
• 页码：304-316
• 全文大小：390 K

文摘

Epileptic encephalopathies of infancy and childhood comprise a large, heterogeneous group of severe epilepsies characterised by several seizure types, frequent epileptiform activity on EEG, and developmental slowing or regression. The encephalopathies include many age-related electroclinical syndromes with specific seizure types and EEG features. With the molecular revolution, the number of known monogenic determinants underlying the epileptic encephalopathies has grown rapidly. De-novo dominant mutations are frequently identified; somatic mosaicism and recessive disorders are also seen. Several genes can cause one electroclinical syndrome, and, conversely, one gene might be associated with phenotypic pleiotropy. Diverse genetic causes and molecular pathways have been implicated, involving ion channels, and proteins needed for synaptic, regulatory, and developmental functions. Gene discovery provides the basis for neurobiological insights, often showing convergence of mechanistic pathways. These findings underpin the development of targeted therapies, which are essential to improve the outcome of these devastating disorders.