RT Journal Article
T1 Developmental and epilepsy spectrum of KCNB1 encephalopathy with long-term outcome.
A1 Bar, Claire
A1 Kuchenbuch, Mathieu
A1 Barcia, Giulia
A1 Schneider, Amy
A1 Jennesson, Mélanie
A1 Le Guyader, Gwenaël
A1 Lesca, Gaetan
A1 Mignot, Cyril
A1 Montomoli, Martino
A1 Parrini, Elena
A1 Isnard, Hervé
A1 Rolland, Anne
A1 Keren, Boris
A1 Afenjar, Alexandra
A1 Dorison, Nathalie
A1 Sadleir, Lynette G
A1 Breuillard, Delphine
A1 Levy, Raphael
A1 Rio, Marlène
A1 Dupont, Sophie
A1 Negrin, Susanna
A1 Danieli, Alberto
A1 Scalais, Emmanuel
A1 De Saint Martin, Anne
A1 El Chehadeh, Salima
A1 Chelly, Jamel
A1 Poisson, Alice
A1 Lebre, Anne-Sophie
A1 Nica, Anca
A1 Odent, Sylvie
A1 Sekhara, Tayeb
A1 Brankovic, Vesna
A1 Goldenberg, Alice
A1 Vrielynck, Pascal
A1 Lederer, Damien
A1 Maurey, Hélène
A1 Terrone, Gaetano
A1 Besmond, Claude
A1 Hubert, Laurence
A1 Berquin, Patrick
A1 Billette de Villemeur, Thierry
A1 Isidor, Bertrand
A1 Freeman, Jeremy L
A1 Mefford, Heather C
A1 Myers, Candace T
A1 Howell, Katherine B
A1 Rodríguez-Sacristán Cascajo, Andrés
A1 Meyer, Pierre
A1 Genevieve, David
A1 Guët, Agnès
A1 Doummar, Diane
A1 Durigneux, Julien
A1 van Dooren, Marieke F
A1 de Wit, Marie Claire Y
A1 Gerard, Marion
A1 Marey, Isabelle
A1 Munnich, Arnold
A1 Guerrini, Renzo
A1 Scheffer, Ingrid E
A1 Kabashi, Edor
A1 Nabbout, Rima
K1 autism spectrum disorders
K1 developmental and epileptic encephalopathy
K1 developmental encephalopathy
K1 drug-resistant epilepsy
K1 potassium channels
K1 sudden unexpected death in epilepsy
AB 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.
YR 2020
FD 2020-09-21
LK http://hdl.handle.net/10668/16285
UL http://hdl.handle.net/10668/16285
LA en
DS RISalud
RD Apr 19, 2025