title: Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.
abstract: OBJECTIVE
  Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening.
  
  
  METHODS
  We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH).
  
  
  RESULTS
  We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%.
  
  
  CONCLUSIONS
  Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening.
authors.affiliation: Pediatric Neurology Department, Timone Children Hospital, Marseille, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Di Meglio
authors.affiliation: INSERM, U1028, CNRS, UMR5292, Laboratory of Molecular Genetics, Lyon, France.
authors.forename: Gaetan
authors.initials: G
authors.lastname: Lesca
authors.affiliation: Pediatric Neurology Department, Timone Children Hospital, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villeneuve
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Medical Genetics Department, Timone Children Hospital, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoste
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Affef
authors.initials: A
authors.lastname: Abidi
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Medical Genetics Department, Timone Children Hospital, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cacciagli
authors.affiliation: Department of Pediatrics, St. Jacques Hospital, Besançon, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Altuzarra
authors.affiliation: Pediatric Neurology Department, Montpellier University Hospital, Montpellier, France.|Institute for Neurosciences of Montpellier (INM), INSERM U 1051, Montpellier, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.affiliation: Pediatric Neurology Department, Trousseau Hospital, AP-HP, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.affiliation: Pediatric Neurology Department, Trousseau Hospital, AP-HP, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Renaldo-Robin
authors.affiliation: Medical Genetics Department, Nantes University Hospital, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Department of Pediatrics, Nantes University Hospital, Nantes, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Gautier
authors.affiliation: Pediatric Neurology Department, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Husson
authors.affiliation: Pediatric Neurology Department, Toulouse University Hospital, Toulouse, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Cances
authors.affiliation: Pediatric Neurology Department, Bicêtre Hospital, Kremlin-Bicêtre, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Metreau
authors.affiliation: Department of Pediatrics, Limoges University Hospital, Limoges, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Laroche
authors.affiliation: Department of Pediatrics, Dijon University Hospital, Dijon, France.
authors.forename: Mondher
authors.initials: M
authors.lastname: Chouchane
authors.affiliation: Pediatric Neurology Department, Lyon University Hospital, Bron, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Ville
authors.affiliation: Pediatric Neurology Department, Lyon University Hospital, Bron, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Marignier
authors.affiliation: Pediatric Neurology Department, Lyon University Hospital, Bron, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Rougeot
authors.affiliation: Medical Genetics Department, St Etienne University Hospital, Saint Priez en Jarez, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Lebrun
authors.affiliation: Pediatric Neurology Department, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint Martin
authors.affiliation: Pediatric Intensive Cares Unit, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Perez
authors.affiliation: Pediatric Neurology Department, Lille University Hospital, Lille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Riquet
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Medical Genetics Department, Timone Children Hospital, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: Medical Genetics Department, Timone Children Hospital, Marseille, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Missirian
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Medical Genetics Department, Timone Children Hospital, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.affiliation: Pediatric Neurology Department, Timone Children Hospital, Marseille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.affiliation: Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
authors.affiliation: Pediatric Neurology Department, Timone Children Hospital, Marseille, France.|Aix Marseille University, INSERM, UMR_S 910, Marseille, France.|Aix Marseille University, GMGF, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
mesh_terms: D017668:Age of Onset; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation; D012189:Retrospective Studies; D017384:Sequence Deletion; D013036:Spasms, Infantile / Q000235:genetics
chemical_list: D051938:Munc18 Proteins; C497937:STXBP1 protein, human
keywords: Early onset epileptic encephalopathy; Genetics; Ohtahara syndrome; Suppression-burst