Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases

Chloé Di Meglio (1) , Gaetan Lesca (2, 3) , Nathalie Villeneuve (1) , Caroline Lacoste (3, 4) , Affef Abidi (3) , Pierre Cacciagli (3, 4) , Cécilia Altuzarra (5) , Agathe Roubertie (6, 7) , Alexandra Afenjar (8) , Florence Renaldo-Robin (8) , Bertrand Isidor (9) , Agnès Gautier (10) , Marie Husson (11) , Claude Cances (12) , Julia Metreau (13) , Cécile Laroche (14) , Mondher Chouchane (15) , Dorothée Ville (16) , Stéphanie Marignier (16) , Christelle Rougeot (17) , Marine Lebrun (18) , Anne de Saint Martin (19) , Alexandra Perez (19) , Audrey Riquet (20) , Catherine Badens (3, 4, 21) , Chantal Missirian (4) , Nicole Philip (4, 3) , Brigitte Chabrol (1, 3) , Laurent Villard (3) , Mathieu Milh (1, 3)

1 Service de pédiatrie et neurologie pédiatrique
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 GMGF - Génétique Médicale et Génomique Fonctionnelle
4 Département de génétique médicale [Hôpital de la Timone - APHM]
5 Service de pédiatrie [CHRU Besançon]
6 CHU - Hôpital Lapeyronie [Montpellier]
7 INM - Institut des Neurosciences de Montpellier
8 CHU Trousseau [APHP]
9 Service de génétique médicale - Unité de génétique clinique [Nantes]
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes
11 CHU Bordeaux
12 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
13 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
14 Service de Pédiatrie médicale [CHU Limoges]
15 Service de pédiatrie (CHU de Dijon)
16 Hôpital Louis Pradel [CHU - HCL]
17 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
18 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
19 Hôpital de Hautepierre [Strasbourg]
20 Service de Neuro-pédiatrie[Lille]
21 Centre de référence maladie rare Thalassémie

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 geno-mic 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%.

Domaines: Sciences du Vivant [q-bio]; Génétique; Médecine humaine et pathologie; Neurosciences [q-bio.NC]

Chloé Di Meglio, Gaetan Lesca, Nathalie Villeneuve, Caroline Lacoste, Affef Abidi, et al.. Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases. Epilepsia, 2015, 56 (12), pp.1931-1940. ⟨10.1111/epi.13214⟩. ⟨hal-01664313⟩