Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome
Claire Bar
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
Search for more papers by this authorMathieu Kuchenbuch
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
Search for more papers by this authorGiulia Barcia
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
Search for more papers by this authorAmy Schneider
Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Search for more papers by this authorMélanie Jennesson
Department of Pediatrics, American Memorial Hospital, Reims, France
Search for more papers by this authorGwenaël Le Guyader
Department of Genetics, Poitiers University Hospital Center, Poitiers Cedex, France
EA3808–NEUVACOD Neurovascular and Cognitive Disorders Unit, University of Poitiers, Poitiers, France
Search for more papers by this authorGaetan Lesca
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
Search for more papers by this authorCyril Mignot
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
Search for more papers by this authorMartino Montomoli
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorElena Parrini
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorHervé Isnard
Pediatric Neurologist, Medical Office, Lyon, France
Search for more papers by this authorAnne Rolland
Department of Pediatrics, Nantes University Hospital Center, Nantes, France
Search for more papers by this authorBoris Keren
Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Search for more papers by this authorAlexandra Afenjar
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
Search for more papers by this authorNathalie Dorison
Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Paris, France
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorLynette G. Sadleir
Department of Pediatrics and Child Health, University of Otago, Wellington, New Zealand
Search for more papers by this authorDelphine Breuillard
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
Search for more papers by this authorRaphael Levy
Department of Pediatric Radiology, Necker-Enfants Malades Hospital, Paris, France
Search for more papers by this authorMarlène Rio
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
Search for more papers by this authorSophie Dupont
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
Epileptology Unit and Rehabilitation Unit, AP-HP, Pitie-Salpêtrière-Charles Foix Hospital, Paris, France
Search for more papers by this authorSusanna Negrin
Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS E. Medea, Treviso, Italy
Search for more papers by this authorAlberto Danieli
Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS E. Medea, Treviso, Italy
Search for more papers by this authorEmmanuel Scalais
Pediatric Neurology Unit, Luxembourg Hospital Center, Luxembourg City, Luxembourg
Search for more papers by this authorAnne De Saint Martin
Department of Pediatric Neurology, Strasbourg University Hospital, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorSalima El Chehadeh
Department of Medical Genetics, Strasbourg University Hospitals, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorJamel Chelly
Department of Medical Genetics, Strasbourg University Hospitals, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorAlice Poisson
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
Search for more papers by this authorAnne-Sophie Lebre
Reims University Hospital Center, Maison Blanche Hospital, Biology Department, Reims, France
Search for more papers by this authorAnca Nica
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
Search for more papers by this authorSylvie Odent
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
Search for more papers by this authorTayeb Sekhara
Department of Pediatric Neurology, C.H.I.R.E.C, Brussels, Belgium
Search for more papers by this authorVesna Brankovic
Clinic for Child Neurology and Psychiatry, Belgrade, Serbia
Search for more papers by this authorAlice Goldenberg
Reference Center for Developmental Anomalies and Malformation Syndromes, Rouen University Hospital Center, Rouen, France
Search for more papers by this authorPascal Vrielynck
Reference Center for Refractory Epilepsy, Catholic University of Louvain, William Lennox Neurological Hospital, Ottignies, Belgium
Search for more papers by this authorHélène Maurey
Department of Pediatric Neurology, AP-HP, Bicêtre University Hospital, Kremlin Bicêtre, France
Search for more papers by this authorGaetano Terrone
Department of Translational Medical Sciences, Section of Pediatrics, Child Neurology Unit, Federico II University, Naples, Italy
Search for more papers by this authorClaude Besmond
Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France
Search for more papers by this authorLaurence Hubert
Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France
Search for more papers by this authorPatrick Berquin
Department of Pediatric Neurology, Amiens-Picardie University Hospital Center, University of Picardy Jules Verne, Amiens, France
Search for more papers by this authorThierry Billette de Villemeur
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorBertrand Isidor
Department of Clinical Genetics, Nantes University Hospital Center, Nantes, France
Search for more papers by this authorJeremy L. Freeman
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Search for more papers by this authorHeather C. Mefford
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, United States
Search for more papers by this authorCandace T. Myers
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, United States
Search for more papers by this authorKatherine B. Howell
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Search for more papers by this authorAndrés Rodríguez-Sacristán Cascajo
Pediatric Neurology Unit, Department of Pediatric, Virgen Macarena Hospital, Seville, Spain
Department of Pediatrics, School of Medicine, University of Seville, Seville, Spain
Search for more papers by this authorPierre Meyer
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
Search for more papers by this authorDavid Genevieve
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
Search for more papers by this authorAgnès Guët
Department of Pediatrics, Louis-Mourier Hospital, Colombes, France
Search for more papers by this authorDiane Doummar
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorJulien Durigneux
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorMarieke F. van Dooren
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorMarie Claire Y. de Wit
Department of Pediatric Neurology and ENCORE Expertise Center, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, the Netherlands
Search for more papers by this authorMarion Gerard
Clinical Genetics, Côte de Nacre University Hospital Center, Caen, France
Search for more papers by this authorIsabelle Marey
Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Search for more papers by this authorArnold Munnich
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
Search for more papers by this authorRenzo Guerrini
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorIngrid E. Scheffer
Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia
Search for more papers by this authorEdor Kabashi
Imagine Institute, Mixed Unit of Research 1163, University of Paris, Sorbonne University, Paris, France
Search for more papers by this authorCorresponding Author
Rima Nabbout
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
Correspondence
Rima Nabbout, Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Necker Enfants Malades Hospital, 149 rue de Sèvres, 75015 Paris, France.
Email: [email protected]
Search for more papers by this authorClaire Bar
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
Search for more papers by this authorMathieu Kuchenbuch
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
Search for more papers by this authorGiulia Barcia
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
Search for more papers by this authorAmy Schneider
Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Search for more papers by this authorMélanie Jennesson
Department of Pediatrics, American Memorial Hospital, Reims, France
Search for more papers by this authorGwenaël Le Guyader
Department of Genetics, Poitiers University Hospital Center, Poitiers Cedex, France
EA3808–NEUVACOD Neurovascular and Cognitive Disorders Unit, University of Poitiers, Poitiers, France
Search for more papers by this authorGaetan Lesca
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
Search for more papers by this authorCyril Mignot
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
Search for more papers by this authorMartino Montomoli
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorElena Parrini
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorHervé Isnard
Pediatric Neurologist, Medical Office, Lyon, France
Search for more papers by this authorAnne Rolland
Department of Pediatrics, Nantes University Hospital Center, Nantes, France
Search for more papers by this authorBoris Keren
Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Search for more papers by this authorAlexandra Afenjar
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
Search for more papers by this authorNathalie Dorison
Pediatric Neurosurgery Department, Rothschild Foundation Hospital, Paris, France
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorLynette G. Sadleir
Department of Pediatrics and Child Health, University of Otago, Wellington, New Zealand
Search for more papers by this authorDelphine Breuillard
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
Search for more papers by this authorRaphael Levy
Department of Pediatric Radiology, Necker-Enfants Malades Hospital, Paris, France
Search for more papers by this authorMarlène Rio
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
Search for more papers by this authorSophie Dupont
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
Epileptology Unit and Rehabilitation Unit, AP-HP, Pitie-Salpêtrière-Charles Foix Hospital, Paris, France
Search for more papers by this authorSusanna Negrin
Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS E. Medea, Treviso, Italy
Search for more papers by this authorAlberto Danieli
Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, IRCCS E. Medea, Treviso, Italy
Search for more papers by this authorEmmanuel Scalais
Pediatric Neurology Unit, Luxembourg Hospital Center, Luxembourg City, Luxembourg
Search for more papers by this authorAnne De Saint Martin
Department of Pediatric Neurology, Strasbourg University Hospital, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorSalima El Chehadeh
Department of Medical Genetics, Strasbourg University Hospitals, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorJamel Chelly
Department of Medical Genetics, Strasbourg University Hospitals, Hautepierre Hospital, Strasbourg, France
Search for more papers by this authorAlice Poisson
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
Search for more papers by this authorAnne-Sophie Lebre
Reims University Hospital Center, Maison Blanche Hospital, Biology Department, Reims, France
Search for more papers by this authorAnca Nica
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
Search for more papers by this authorSylvie Odent
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
Search for more papers by this authorTayeb Sekhara
Department of Pediatric Neurology, C.H.I.R.E.C, Brussels, Belgium
Search for more papers by this authorVesna Brankovic
Clinic for Child Neurology and Psychiatry, Belgrade, Serbia
Search for more papers by this authorAlice Goldenberg
Reference Center for Developmental Anomalies and Malformation Syndromes, Rouen University Hospital Center, Rouen, France
Search for more papers by this authorPascal Vrielynck
Reference Center for Refractory Epilepsy, Catholic University of Louvain, William Lennox Neurological Hospital, Ottignies, Belgium
Search for more papers by this authorHélène Maurey
Department of Pediatric Neurology, AP-HP, Bicêtre University Hospital, Kremlin Bicêtre, France
Search for more papers by this authorGaetano Terrone
Department of Translational Medical Sciences, Section of Pediatrics, Child Neurology Unit, Federico II University, Naples, Italy
Search for more papers by this authorClaude Besmond
Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France
Search for more papers by this authorLaurence Hubert
Translational Genetics, National Institute of Health and Medical Research Mixed Unit of Research 1163, Imagine Institute, University of Paris, Paris, France
Search for more papers by this authorPatrick Berquin
Department of Pediatric Neurology, Amiens-Picardie University Hospital Center, University of Picardy Jules Verne, Amiens, France
Search for more papers by this authorThierry Billette de Villemeur
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorBertrand Isidor
Department of Clinical Genetics, Nantes University Hospital Center, Nantes, France
Search for more papers by this authorJeremy L. Freeman
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Search for more papers by this authorHeather C. Mefford
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, United States
Search for more papers by this authorCandace T. Myers
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, United States
Search for more papers by this authorKatherine B. Howell
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Search for more papers by this authorAndrés Rodríguez-Sacristán Cascajo
Pediatric Neurology Unit, Department of Pediatric, Virgen Macarena Hospital, Seville, Spain
Department of Pediatrics, School of Medicine, University of Seville, Seville, Spain
Search for more papers by this authorPierre Meyer
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
Search for more papers by this authorDavid Genevieve
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
Search for more papers by this authorAgnès Guët
Department of Pediatrics, Louis-Mourier Hospital, Colombes, France
Search for more papers by this authorDiane Doummar
Department of Pediatric Neurology, AP-HP, Armand Trousseau Hospital, Sorbonne University, Paris, France
Search for more papers by this authorJulien Durigneux
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorMarieke F. van Dooren
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorMarie Claire Y. de Wit
Department of Pediatric Neurology and ENCORE Expertise Center, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, the Netherlands
Search for more papers by this authorMarion Gerard
Clinical Genetics, Côte de Nacre University Hospital Center, Caen, France
Search for more papers by this authorIsabelle Marey
Department of Genetics, Rare Causes of Intellectual Disability Reference Center, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Search for more papers by this authorArnold Munnich
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
Search for more papers by this authorRenzo Guerrini
Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, University of Florence, Florence, Italy
Search for more papers by this authorIngrid E. Scheffer
Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia
Search for more papers by this authorEdor Kabashi
Imagine Institute, Mixed Unit of Research 1163, University of Paris, Sorbonne University, Paris, France
Search for more papers by this authorCorresponding Author
Rima Nabbout
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
Correspondence
Rima Nabbout, Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Necker Enfants Malades Hospital, 149 rue de Sèvres, 75015 Paris, France.
Email: [email protected]
Search for more papers by this authorAbstract
Objective
We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy.
Methods
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.
Results
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.
Significance
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.
CONFLICT OF INTEREST
I.E.S. serves/has served on the editorial boards of the Annals of Neurology, Neurology, and Epileptic Disorders; may accrue future revenue on pending patent WO61/010176 (filed in 2008), "Therapeutic Compound"; has a patent for SCN1A testing held by Bionomics and licensed to various diagnostic companies; has a patent "Molecular Diagnostic/Theranostic Target for Benign Familial Infantile Epilepsy (BFIE) [PRRT2]" 2011904493, 2012900190, and PCT/AU2012/001321 (TECH ID: 2012-009), with royalties paid; has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, and Eisai; has consulted for UCB, Zynerba Pharmaceuticals, and Ovid Therapeutics; and receives/has received research support from the National Health and Medical Research Council of Australia, Health Research Council of New Zealand, CURE, Australian Epilepsy Research Fund, March of Dimes, and National Institutes of Health/National Institute of Neurological Disorders and Stroke. None of the other authors has any conflict of interest to disclose.
Supporting Information
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| epi16679-sup-0001-TableS1.xlsxapplication/excel, 18.9 KB | Table S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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