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https://ahro.austin.org.au/austinjspui/handle/1/24952| Title: | Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome. | Austin Authors: | Bar, Claire;Kuchenbuch, Mathieu;Barcia, Giulia;Schneider, Amy ;Jennesson, Mélanie;Le Guyader, Gwenaël;Lesca, Gaetan;Mignot, Cyril;Montomoli, Martino;Parrini, Elena;Isnard, Hervé;Rolland, Anne;Keren, Boris;Afenjar, Alexandra;Dorison, Nathalie;Sadleir, Lynette G;Breuillard, Delphine;Levy, Raphael;Rio, Marlène;Dupont, Sophie;Negrin, Susanna;Danieli, Alberto;Scalais, Emmanuel;De Saint Martin, Anne;El Chehadeh, Salima;Chelly, Jamel;Poisson, Alice;Lebre, Anne-Sophie;Nica, Anca;Odent, Sylvie;Sekhara, Tayeb;Brankovic, Vesna;Goldenberg, Alice;Vrielynck, Pascal;Lederer, Damien;Maurey, Hélène;Terrone, Gaetano;Besmond, Claude;Hubert, Laurence;Berquin, Patrick;Billette de Villemeur, Thierry;Isidor, Bertrand;Freeman, Jeremy L;Mefford, Heather C;Myers, Candace T;Howell, Katherine B;Rodríguez-Sacristán Cascajo, Andrés;Meyer, Pierre;Genevieve, David;Guët, Agnès;Doummar, Diane;Durigneux, Julien;van Dooren, Marieke F;de Wit, Marie Claire Y;Gerard, Marion;Marey, Isabelle;Munnich, Arnold;Guerrini, Renzo;Scheffer, Ingrid E ;Kabashi, Edor;Nabbout, Rima | Affiliation: | Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia Murdoch Children's Research Institute, Melbourne, Victoria, Australia Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia Neurology Department, Center for Clinical Research (CIC 1414), Rennes University Hospital, Rennes, France Laboratory of Signal Processing, National Institute of Health and Medical Research Mixed Unit of Research 1099, Rennes, France Reference Center for Rare Developmental Abnormalities CLAD-Ouest, Rennes University Hospital Center, Rennes, France National Center for Scientific Research Mixed Unit of Research 6290, Institute of Genetics and Development of Rennes (IGDR), University of Rennes, Rennes, France Pediatric Neurology Unit, Department of Pediatric, Virgen Macarena Hospital, Seville, Spain Department of Pediatrics, School of Medicine, University of Seville, Seville, Spain Department of Pediatric Neurology, Montpellier University Hospital Center, Montpellier, France PhyMedExp, National Institute of Health and Medical Research, U1046, National Center for Scientific Research Mixed Unit of Research 9214, University of Montpellier, Montpellier, France Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades Hospital, Paris, France Imagine Institute, Mixed Unit of Research 1163, University of Paris, Sorbonne University, Paris, France Department of Clinical Genetics, AP-HP, Necker-Enfants Malades Hospital, Paris, France Department of Genetics, Poitiers University Hospital Center, Poitiers Cedex, France EA3808-NEUVACOD Neurovascular and Cognitive Disorders Unit, University of Poitiers, Poitiers, France Department of Genetics, Lyon Civil Hospices, Lyon, France NeuroMyoGène Institute, National Center for Scientific Research, Mixed Unit of Research 5310, National Institute of Health and Medical Research U1217, University of Lyon, Claude Bernard Lyon 1 University, Villeurbanne, France National Institute of Health and Medical Research, U1127, National Center for Scientific Research Mixed Unit of Research 7225, Pierre and Marie Curie University Paris 6 Mixed Unit of Research S1127, Brain and Spine Institute, Sorbonne University, Paris, France Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Paris, France Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France Department of Clinical Genetics, AP-HP, Necker-Enfants Malades Hospital, Paris, France Laboratory of Developmental Brain Disorders, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, Sorbonne University, Paris, France Epileptology Unit and Rehabilitation Unit, AP-HP, Pitie-Salpêtrière-Charles Foix Hospital, Paris, France Department of Pediatrics, American Memorial Hospital, Reims, France Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy Pediatric Neurologist, Medical Office, Lyon, France Department of Pediatrics, Nantes University Hospital Center, Nantes, France Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France Department of Genetics and Medical Embryology, Reference Center for Malformations and Congenital Diseases of the Cerebellum and Rare Causes of Intellectual Disabilities, Sorbonne University, AP-HP, Trousseau Hospital, Paris, France Department of Pediatrics and Child Health, University of Otago, Wellington, New Zealand Department of Pediatric Radiology, Necker-Enfants Malades Hospital, Paris, France Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS E. Medea, Treviso, Italy Pediatric Neurology Unit, Luxembourg Hospital Center, Luxembourg City, Luxembourg Department of Pediatric Neurology, Strasbourg University Hospital, Hautepierre Hospital, Strasbourg, France Department of Medical Genetics, Strasbourg University Hospitals, Hautepierre Hospital, Strasbourg, France GénoPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, le Vinatier Hospital Center and EDR-Psy Team (National Center for Scientific Research and Lyon 1 Claude Bernard University), Villeurbanne, France Reims University Hospital Center, Maison Blanche Hospital, Biology Department, Reims, France Department of Pediatric Neurology, C.H.I.R.E.C, Brussels, Belgium Clinic for Child Neurology and Psychiatry, Belgrade, Serbia Reference Center for Developmental Anomalies and Malformation Syndromes, Rouen University Hospital Center, Rouen, France Reference Center for Refractory Epilepsy, Catholic University of Louvain, William Lennox Neurological Hospital, Ottignies, Belgium Human Genetic Center, IPG, Gosselies, Belgium Department of Pediatric Neurology, AP-HP, Bicêtre University Hospital, Kremlin Bicêtre, France Department of Translational Medical Sciences, Section of Pediatrics, Child Neurology Unit, Federico II University, Naples, Italy Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France Department of Pediatric Neurology, Amiens-Picardie University Hospital Center, University of Picardy Jules Verne, Amiens, France Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France Department of Clinical Genetics, Nantes University Hospital Center, Nantes, France Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, United States Department of Medical Genetics, Rare Disease, and Personalized Medicine, IRMB, University of Montpellier, National Institute of Health and Medical Research, Montpellier University Hospital Center, Montpellier, France Department of Pediatrics, Louis-Mourier Hospital, Colombes, France Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands Department of Pediatric Neurology and ENCORE Expertise Center, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands Clinical Genetics, Côte de Nacre University Hospital Center, Caen, France Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy Imagine Institute, Mixed Unit of Research 1163, University of Paris, Sorbonne University, Paris, France |
Issue Date: | Nov-2020 | Date: | 2020-09-21 | Publication information: | Epilepsia 2020; 61(11): 2461-2473 | Abstract: | We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/24952 | DOI: | 10.1111/epi.16679 | ORCID: | 0000-0003-1489-0211 0000-0002-5944-2204 0000-0001-7691-9492 0000-0002-5355-7115 0000-0003-2080-8253 0000-0002-2311-2174 |
Journal: | Epilepsia | PubMed URL: | 32954514 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/32954514/ | Type: | Journal Article | Subjects: | autism spectrum disorders developmental and epileptic encephalopathy developmental encephalopathy drug-resistant epilepsy potassium channels sudden unexpected death in epilepsy |
| Appears in Collections: | Journal articles |
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