Developmental and epilepsy spectrum of KCNB1 encephalopathy with long‐term outcome

• DOI: 10.1111/epi.16679
• Publication Date: 2020-09-21T09:32:57Z
• Authors: Claire Bar; Mathieu Kuchenbuch; Giulia Barcia; Amy Schneider; Mélanie Jennesson; Gwenaël Le Guyader; Gaetan Lesca; Cyril Mignot; Martino Montomoli; Elena Parrini; Hervé Isnard; Anne Rolland; Boris Keren; Alexandra Afenjar; Nathalie Dorison; Lynette G. Sadleir; Delphine Breuillard; Raphael Levy; Marlène Rio; Sophie Dupont; Susanna Negrin; Alberto Danieli; Emmanuel Scalais; Anne De Saint Martin; Salima El Chehadeh; Jamel Chelly; Alice Poisson; Anne‐Sophie Lebre; Anca Nica; Sylvie Odent; Tayeb Sekhara; Vesna Brankovic; Alice Goldenberg; Pascal Vrielynck; Damien Lederer; Hélène Maurey; Gaetano Terrone; Claude Besmond; Laurence Hubert; Patrick Berquin; Thierry Billette ...; Bertrand Isidor; Jeremy L. Freeman; Heather C. Mefford; Candace T. Myers; Katherine B. Howell; Andrés Rodríguez‐...; Pierre Meyer; David Genevieve; Agnès Guët; Diane Doummar; Julien Durigneux; Marieke F. van Do...; Marie Claire Y. d...; Marion Gerard; Isabelle Marey; Arnold Munnich; Renzo Guerrini; Ingrid E. Scheffer; Edor Kabashi; Rima Nabbout
• Keywords: Adult; Male; Time Factors; Adolescent; [SDV]Life Sciences [q-bio]; autism spectrum disorders; EMC OR-01; 610; autism spectrum disorders; developmental and epileptic encephalopathy; developmental encephalopathy; drug-resistant epilepsy; potassium channels; sudden unexpected death in epilepsy; Cohort Studies; Young Adult; 03 medical and health sciences; drug-resistant epilepsy; Shab Potassium Channels; 0302 clinical medicine; 616; Humans; developmental and epileptic encephalopathy; Child; Retrospective Studies; sudden unexpected death in epilepsy; Brain Diseases; developmental encephalopathy; Epilepsy; Genetic Variation; Infant; Electroencephalography; potassium channels; 3. Good health; Treatment Outcome; Child, Preschool; Female; EMC COEUR-09

Abstract Objective We aimed to delineate the phenotypic spectrum and long‐term outcome of individuals with KCNB1 encephalopathy. Methods collected genetic, clinical, electroencephalographic, imaging data pathogenic variants recruited through an international collaboration, support family association “KCNB1 France.” Patients were classified as having developmental epileptic encephalopathy (DEE) or (DE). In addition, we reviewed published cases provided in patients older than 12 years from our series literature. Results Our included 36 (21 males, median age = 10 years, range 1.6 months‐34 years). Twenty (56%) had DEE infantile onset seizures (seizure months, days‐3.5 years), whereas 16 (33%) DE late epilepsy 5 18 months‐25 years) without six. Cognitive impairment was more severe compared those DE. Analysis 73 (36 37 nine reports) showed delay all profound intellectual disability 67% (n 41/61) autistic features 56% 32/57). Long‐term 22 (14 eight individuals) poor cognitive, psychiatric, behavioral outcome. Epilepsy course variable. Missense associated frequent truncating variants. Significance study describes encephalopathy, which varies epilepsy. Although cognitive is worse DEE, for most missense are Further understanding disease mechanisms should facilitate development targeted therapies, much needed improve neurodevelopmental prognosis.