Defining the phenotypic spectrum of SLC6A1 mutations

Autor:	Elena Gardella, Diane Doummar, Orrin Devinsky, Nicola Specchio, Holly Dubbs, Lance H. Rodan, Caroline Nava, Elise Schaefer, Jessica E. Shaw, Desiree Czapansky-Beilman, Tarja Linnankivi, Rikke S. Møller, Helenius J. Schelhaas, Kathrine L. Helbig, Jakob Christensen, Jamel Chelly, Gemma L. Carvill, Sarah E. Hopkins, Sara Chadwick Reichert, Marina Trivisano, Amélie Piton, Candace T. Myers, Pasquale Striano, Katrine M Johannesen, Alexandra Afenjar, Judith S. Verhoeven, John Millichap, Yongjin Yoo, Oriano Mecarelli, Murim Choi, Jong Hee Chae, Joseph G. Gleeson, Heather C Mefford, Gaetan Lesca, Laura Pisani, Boris Keren, Sha Tang, Marie Thérèse Abi-Warde, Carolina Courage, Ingo Helbig, Deb K. Pal, Guido Rubboli, Lynne M. Bird, Manuela Pendziwiat, Cyril Mignot, Shan Tang, J. Lawrence Merritt, Yvonne G. Weber, Anna-Elina Lehesjoki, Wen-Hann Tan, Anne de Saint Martin, Mark Nespeca
Přispěvatelé:	University of Southern Denmark (SDU), CHU Strasbourg, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Boston Children's Hospital, Seoul National University [Seoul] (SNU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Genoa (UNIGE), Children’s Hospital of Philadelphia (CHOP )
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Male 0301 basic medicine Pediatrics Epilepsies Myoclonic Epilepsies Neurodegenerative Epilepsies Myoclonic/complications Intellectual Disability/complications Cohort Studies Epilepsy 0302 clinical medicine 2.1 Biological and endogenous factors Neurodevelopmental Disorders/complications Aetiology Valproic Acid/therapeutic use Child Atonic seizure Ataxia/complications Seizure types Anticonvulsants/therapeutic use Electroencephalography MAE Language Development Disorders/complications Phenotype Treatment Outcome Neurology Child Preschool Neurological Speech delay Anticonvulsants Epilepsy Generalized Female medicine.symptom Partial Adult GABA Plasma Membrane Transport Proteins medicine.medical_specialty SLC6A1 epilepsy epilepsy genetics Adolescent Epilepsies Partial/complications Epilepsy Generalized/complications Clinical Sciences Mutation Missense GABA Plasma Membrane Transport Proteins/genetics Status epilepticus Article Young Adult 03 medical and health sciences Childhood absence epilepsy Clinical Research Intellectual Disability Behavioral and Social Science Genetics medicine Humans Language Development Disorders Generalized epilepsy Preschool Genetic Association Studies Neurology & Neurosurgery Generalized business.industry Valproic Acid Neurosciences medicine.disease Brain Disorders 030104 developmental biology Myoclonic astatic epilepsy [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Neurodevelopmental Disorders Mutation Ataxia Epilepsies Partial Neurology (clinical) Missense Myoclonic business 030217 neurology & neurosurgery
Zdroj:	Epilepsia Epilepsia, Wiley, 2018, 32 (2), pp.389-402. ⟨10.1111/epi.13986⟩ Johannesen, K M, Gardella, E, Linnankivi, T, Courage, C, de Saint Martin, A, Lehesjoki, A E, Mignot, C, Afenjar, A, Lesca, G, Abi-Warde, M T, Chelly, J, Piton, A, Merritt, J L, Rodan, L H, Tan, W H, Bird, L M, Nespeca, M, Gleeson, J G, Yoo, Y, Choi, M, Chae, J H, Czapansky-Beilman, D, Reichert, S C, Pendziwiat, M, Verhoeven, J S, Schelhaas, H J, Devinsky, O, Christensen, J, Specchio, N, Trivisano, M, Weber, Y G, Nava, C, Keren, B, Doummar, D, Schaefer, E, Hopkins, S, Dubbs, H, Shaw, J E, Pisani, L, Myers, C T, Tang, S, Tang, S, Pal, D K, Millichap, J J, Carvill, G L, Helbig, K L, Mecarelli, O, Striano, P, Rubboli, G & Møller, R S 2018, ' Defining the phenotypic spectrum of SLC6A1 mutations ', Epilepsia, vol. 59, no. 2, pp. 389-402 . https://doi.org/10.1111/epi.13986 Johannesen, K M, Gardella, E, Linnankivi, T, Courage, C, de Saint Martin, A, Lehesjoki, A-E, Mignot, C, Afenjar, A, Lesca, G, Abi-Warde, M-T, Chelly, J, Piton, A, Merritt, J L, Rodan, L H, Tan, W-H, Bird, L M, Nespeca, M, Gleeson, J G, Yoo, Y, Choi, M, Chae, J-H, Czapansky-Beilman, D, Reichert, S C, Pendziwiat, M, Verhoeven, J S, Schelhaas, H J, Devinsky, O, Christensen, J, Specchio, N, Trivisano, M, Weber, Y G, Nava, C, Keren, B, Doummar, D, Schaefer, E, Hopkins, S, Dubbs, H, Shaw, J E, Pisani, L, Myers, C T, Tang, S, Tang, S, Pal, D K, Millichap, J J, Carvill, G L, Helbig, K L, Mecarelli, O, Striano, P, Helbig, I, Rubboli, G, Mefford, H C & Møller, R S 2018, ' Defining the phenotypic spectrum of SLC6A1 mutations ', Epilepsia, vol. 59, no. 2, pp. 389-402 . https://doi.org/10.1111/epi.13986 Epilepsia, vol 59, iss 2
ISSN:	0013-9580
DOI:	10.1111/epi.13986⟩
Popis:	OBJECTIVE: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients.METHODS: We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.RESULTS: Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).SIGNIFICANCE: Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
Databáze:	OpenAIRE
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