Andrea Accogli1, Gert Wiegand1, Marcello Scala1, Caterina Cerminara1, Michele Iacomino1, Antonella Riva1, Barbara Carlini1, Letizia Camerota1, Vincenzo Belcastro1, Paolo Prontera1, Alberto Fernández-Jaén1, Nerses Bebek1, Paolo Scudieri1, Simona Baldassari1, Vincenzo Salpietro1, Giuseppe Novelli1, Chiara De Luca1, Celina von Stülpnagel1, Felicitas Kluger1, Gerhard Josef Kluger1, Gabriele Christine Wohlrab1, Georgia Ramantani1, David Lewis-Smith1, Rhys H Thomas1, Ming Lai1, Alberto Verrotti1, Salvatore Striano2, Christel Depienne1, Carlo Minetti1, Fabio Benfenati1, Francesco Brancati1, Federico Zara2, Pasquale Striano2. 1. From IRCCS Istituto Giannina Gaslini (A.A., M.S., M.I., A.R., B.C., P.S., S.B., V.D.S., C.M., F.Z., P.S.); Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) (A.A., M.S., P.S., V.D.S., C.M., F.Z., P.S.), University of Genoa, Italy; Neuropediatrics Section of the Department of Pediatrics (G.W.), Asklepios Clinic Hamburg Nord-Heidberg, Hamburg; Department of Pediatric and Adolescent Medicine II (Neuropediatrics, Social Pediatrics) (G.W.), University Medical Centre Schleswig-Holstein, Kiel, Germany; Department of Neurosciences (C.C., C.D.L.), Pediatric Neurology Unit, Tor Vergata University, Roma; Human Genetics (L.C., F. Brancati), Department of Life, Health, and Environmental Sciences, and Department of Pediatrics (A.V.), University of L'Aquila; Child Neuropsychiatry Unit (V.B.), Department of Mental Health, ASST-LARIANA, Como; Medical Genetics Unit (P.P.), "S. Maria della Misericordia" Hospital, Perugia, Italy; Department of Pediatric Neurology (A.F.-J.), Hospital Universitario Quirónsalud and Universidad Europea de Madrid, Madrid, Spain; Istanbul University Istanbul Faculty of Medicine (N.B.), Department of Neurology, Turkey; Department of Biomedicine and Prevention (G.N.), Tor Vergata University of Rome; IRCCS Neuromed (G.N.), Pozzilli, Italy; Department of Pharmacology (G.N.), School of Medicine, University of Nevada, Reno; Department of Pediatrics (C.v.S.), University Hospital Munich, Germany; Paracelsus Medical University (C.v.S.), Salzburg, Austria; Epilepsy Center for Children and Adolescents (F.K., G.J.K.), Vogtareuth, Germany; Department of Neuropediatrics (G.C.W., G.R.), University Children's Hospital Zurich, Switzerland; Translational and Clinical Research Institute (D.L.-S., R.H.T., M.L.), Newcastle University; Department of Clinical Neurosciences (D.L.-S., R.H.T., M.L.), Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, UK; Epilepsy Center (S.S.), Federico II University, Napoli, Italy; Institute of Human Genetics (C.D.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institut du Cerveau et de la Moelle épinière (ICM) (C.D.), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, Paris, France; Center for Synaptic Neuroscience and Technology (F.Benfenati), Istituto Italiano di Tecnologia; IRCCS Ospedale Policlinico San Martino (F. Benfenati), Genoa; and Human Functional Genomics (F. Brancati), IRCCS San Raffaele Pisana, Rome, Italy. 2. From IRCCS Istituto Giannina Gaslini (A.A., M.S., M.I., A.R., B.C., P.S., S.B., V.D.S., C.M., F.Z., P.S.); Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) (A.A., M.S., P.S., V.D.S., C.M., F.Z., P.S.), University of Genoa, Italy; Neuropediatrics Section of the Department of Pediatrics (G.W.), Asklepios Clinic Hamburg Nord-Heidberg, Hamburg; Department of Pediatric and Adolescent Medicine II (Neuropediatrics, Social Pediatrics) (G.W.), University Medical Centre Schleswig-Holstein, Kiel, Germany; Department of Neurosciences (C.C., C.D.L.), Pediatric Neurology Unit, Tor Vergata University, Roma; Human Genetics (L.C., F. Brancati), Department of Life, Health, and Environmental Sciences, and Department of Pediatrics (A.V.), University of L'Aquila; Child Neuropsychiatry Unit (V.B.), Department of Mental Health, ASST-LARIANA, Como; Medical Genetics Unit (P.P.), "S. Maria della Misericordia" Hospital, Perugia, Italy; Department of Pediatric Neurology (A.F.-J.), Hospital Universitario Quirónsalud and Universidad Europea de Madrid, Madrid, Spain; Istanbul University Istanbul Faculty of Medicine (N.B.), Department of Neurology, Turkey; Department of Biomedicine and Prevention (G.N.), Tor Vergata University of Rome; IRCCS Neuromed (G.N.), Pozzilli, Italy; Department of Pharmacology (G.N.), School of Medicine, University of Nevada, Reno; Department of Pediatrics (C.v.S.), University Hospital Munich, Germany; Paracelsus Medical University (C.v.S.), Salzburg, Austria; Epilepsy Center for Children and Adolescents (F.K., G.J.K.), Vogtareuth, Germany; Department of Neuropediatrics (G.C.W., G.R.), University Children's Hospital Zurich, Switzerland; Translational and Clinical Research Institute (D.L.-S., R.H.T., M.L.), Newcastle University; Department of Clinical Neurosciences (D.L.-S., R.H.T., M.L.), Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, UK; Epilepsy Center (S.S.), Federico II University, Napoli, Italy; Institute of Human Genetics (C.D.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institut du Cerveau et de la Moelle épinière (ICM) (C.D.), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, Paris, France; Center for Synaptic Neuroscience and Technology (F.Benfenati), Istituto Italiano di Tecnologia; IRCCS Ospedale Policlinico San Martino (F. Benfenati), Genoa; and Human Functional Genomics (F. Brancati), IRCCS San Raffaele Pisana, Rome, Italy pasqualestriano@gaslini.org federicozara@gaslini.org.
Abstract
OBJECTIVE: To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy. METHODS: We investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened. RESULTS: In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common. CONCLUSION: Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by SYN1 mutations.
OBJECTIVE: To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy. METHODS: We investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened. RESULTS: In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common. CONCLUSION: Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by SYN1 mutations.
Authors: Elizabeth C Galizia; Candace T Myers; Costin Leu; Carolien G F de Kovel; Tatiana Afrikanova; Maria Lorena Cordero-Maldonado; Teresa G Martins; Maxime Jacmin; Suzanne Drury; V Krishna Chinthapalli; Hiltrud Muhle; Manuela Pendziwiat; Thomas Sander; Ann-Kathrin Ruppert; Rikke S Møller; Holger Thiele; Roland Krause; Julian Schubert; Anna-Elina Lehesjoki; Peter Nürnberg; Holger Lerche; Aarno Palotie; Antonietta Coppola; Salvatore Striano; Luigi Del Gaudio; Christopher Boustred; Amy L Schneider; Nicholas Lench; Bosanka Jocic-Jakubi; Athanasios Covanis; Giuseppe Capovilla; Pierangelo Veggiotti; Marta Piccioli; Pasquale Parisi; Laura Cantonetti; Lynette G Sadleir; Saul A Mullen; Samuel F Berkovic; Ulrich Stephani; Ingo Helbig; Alexander D Crawford; Camila V Esguerra; Dorothee G A Kasteleijn-Nolst Trenité; Bobby P C Koeleman; Heather C Mefford; Ingrid E Scheffer; Sanjay M Sisodiya Journal: Brain Date: 2015-03-17 Impact factor: 13.501
Authors: Danique R M Vlaskamp; Benjamin J Shaw; Rosemary Burgess; Davide Mei; Martino Montomoli; Han Xie; Candace T Myers; Mark F Bennett; Wenshu XiangWei; Danielle Williams; Saskia M Maas; Alice S Brooks; Grazia M S Mancini; Ingrid M B H van de Laar; Johanna M van Hagen; Tyson L Ware; Richard I Webster; Stephen Malone; Samuel F Berkovic; Renate M Kalnins; Federico Sicca; G Christoph Korenke; Conny M A van Ravenswaaij-Arts; Michael S Hildebrand; Heather C Mefford; Yuwu Jiang; Renzo Guerrini; Ingrid E Scheffer Journal: Neurology Date: 2018-12-12 Impact factor: 11.800