Case Reports

. 2021 Aug 10;97(6):e577-e586.

doi: 10.1212/WNL.0000000000012298. Epub 2021 Jun 2.

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy

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

Affiliations

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.

PMID: 34078716
PMCID: PMC8424500
DOI: 10.1212/WNL.0000000000012298

Case Reports

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy

Andrea Accogli et al. Neurology. 2021.

. 2021 Aug 10;97(6):e577-e586.

doi: 10.1212/WNL.0000000000012298. Epub 2021 Jun 2.

Authors

Affiliations

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.

PMID: 34078716
PMCID: PMC8424500
DOI: 10.1212/WNL.0000000000012298

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.

PubMed Disclaimer

Figures

**Figure 1. Pedigrees and *SYN1* Mutations of Affected Patients**
(A) Pedigree of the 10 families showing affected members with bathing epilepsy (BE) (shaded in gray) and healthy female carriers (indicated with a central dot); the uncle of family 2 (II:3) with unprovoked seizure is shown in light gray. (B) Nonsense, frameshift, and missense variants in *SYN1* (NM_006950.3) are depicted along with the Synapsin-1 structure (bottom; protein domains: A; B, linker; C, actin-binding and synaptic-vesicle binding; D, Pro-rich linker; E), and splicing variants are displayed along the genomic locus (top). *SYN1* variants related to BE are in red, and those linked to other clinical presentations than BE are in black. Variants identified in our cohort with BE are in bold.

Figure 2. Ictal EEG in 2 Patients With *SYN1*
(A) Ictal-video EEG (after bathing) of participant II:4 of family 6 showing the onset of seizure with initial theta high-voltage polymorphic activity over the frontal-temporal region. (B) Ictal-video EEG (after bathing) of participant II:3 of family 7 showing high-voltage polymorphic theta activity over the right frontal-temporal area.

See this image and copyright information in PMC

References

1. Okudan ZV, Özkara Ç. Reflex epilepsy: triggers and management strategies. Neuropsychiatr Dis Treat. 2018;14:327-337. - PMC - PubMed
1. Striano S, Coppola A, del Gaudio L, Striano P. Reflex seizures and reflex epilepsies: old models for understanding mechanisms of epileptogenesis. Epilepsy Res. 2012;100(1-2):1-11. - PubMed
1. Koepp MJ, Caciagli L, Pressler RM, Lehnertz K, Beniczky S. Reflex seizures, traits, and epilepsies: from physiology to pathology. Lancet Neurol. 2016;15(1):92-105. - PubMed
1. Michelucci R, Mecarelli O, Bovo G, et al. . A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures. Neurology. 2007;68(24):2150-2151. - PubMed
1. Galizia EC, Myers CT, Leu C, et al. . CHD2 variants are a risk factor for photosensitivity in epilepsy. Brain. 2015;138(pt 5):1198-1207. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Grants and funding

203914/Z/16/Z/WT_/Wellcome Trust/United Kingdom

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy

Affiliations

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources