The expanding field of genetic developmental and epileptic encephalopathies: current understanding and future perspectives.

Alexis Arzimanoglou, Simona Balestrini, Jo M Wilmshurst, Marina Trivisano, Nicola Specchio, Federico Vigevano, Eleonora Aronica, Sergiusz Jozwiak, Paolo Curatolo, Rima Nabbout, Stéphane Auvin, J Helen Cross, Gaia Colasante

Journal: The Lancet. Child & adolescent health 2024;8(11):821-834

PMID: 39419567

Abstract

Recent advances in genetic testing technologies have revolutionised the identification of genetic abnormalities in early onset developmental and epileptic encephalopathies (DEEs). In this Review, we provide an update on the expanding landscape of genetic factors contributing to DEEs, encompassing over 800 reported genes. We focus on the cellular and molecular mechanisms driving epileptogenesis, with an emphasis on emerging therapeutic strategies and effective treatment options. We explore noteworthy, novel genes linked to DEE phenotypes, such as gBRAT-1 and GNAO1, and gene families such as GRIN and HCN. Understanding the network-level effects of gene variants will pave the way for potential gene therapy applications. Given the diverse comorbidities associated with DEEs, a multidisciplinary team approach is essential. Despite ongoing efforts and improved genetic testing, DEEs lack a cure, and treatment complexities persist. This Review underscores the necessity for larger international prospective studies focusing on both seizure outcomes and developmental trajectories.

Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Address: Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesu' Children's Hospital IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies, EpiCARE, Rome, Italy. Electronic address: [email protected].; Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesu' Children's Hospital IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies, EpiCARE, Rome, Italy.; Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Department of (Neuro)Pathology, Amsterdam, Netherlands; Stichting Epilepsie Instellingen Nederland, Heemstede, Netherlands.; Neuroscience Department, Meyer Children's Hospital IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies, EpiCARE, Florence, Italy; Neuroscience Department, University of Florence, Florence, Italy; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Paediatric Epilepsy and Neurophysiology Department, Hospital San Juan de Dios, Coordinating member of the European Reference Network on Rare and Complex Epilepsies, EpiCARE, Barcelona, Spain.; Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.; UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.; Research Department, Children's Memorial Health Institute, EpicARE Member, Warsaw, Poland.; Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, South Africa.; Pediatric Neurorehabilitation Department, IRCCS San Raffaele, Rome, Italy.; AP-HP, Service de Neurologie Pédiatrique, Centre de référence Epilepsies Rares, Member of European Reference Network EpiCARE, Hôpital Universitaire Robert-Debré, Paris, France; Université Paris-Cité, INSERM Neuro Diderot, Paris, France; Institut Universitaire de France, Paris, France.; Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker-Enfants Malades Hospital, AP-HP, Member of European Reference Network EpiCARE, Institut Imagine, INSERM, UMR 1163, Université de Paris Cité, Paris, France.; Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy.

Link outs

Subscription / membership required

Bant logo

© Copyright 2026, Nutrition Evidence

NED wishes to thank the following organisations for their support:

We use cookies to improve your experience and analyze site traffic with Google Analytics. By continuing to use our site, you agree to our use of cookies. Learn more.