title: Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.
abstract: Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.
authors: Child Neurology and Psychiatry Unit, S Orsola Malpighi Hospital, University of Bologna, Bologna, Italy. ducciomaria.cordelli@aosp.bo.it
authors: Duccio Maria
authors: DM
authors: Cordelli
authors: Livia
authors: L
authors: Garavelli
authors: Salvatore
authors: S
authors: Savasta
authors: Azzurra
authors: A
authors: Guerra
authors: Alessandro
authors: A
authors: Pellicciari
authors: Lucio
authors: L
authors: Giordano
authors: Silvia
authors: S
authors: Bonetti
authors: Ilaria
authors: I
authors: Cecconi
authors: Anita
authors: A
authors: Wischmeijer
authors: Marco
authors: M
authors: Seri
authors: Simonetta
authors: S
authors: Rosato
authors: Chiara
authors: C
authors: Gelmini
authors: Elvio
authors: E
authors: Della Giustina
authors: Anna Rita
authors: AR
authors: Ferrari
authors: Nicoletta
authors: N
authors: Zanotta
authors: Roberta
authors: R
authors: Epifanio
authors: Daniele
authors: D
authors: Grioni
authors: Baris
authors: B
authors: Malbora
authors: Isabella
authors: I
authors: Mammi
authors: Francesca
authors: F
authors: Mari
authors: Sabrina
authors: S
authors: Buoni
authors: Rosa
authors: R
authors: Mostardini
authors: Salvatore
authors: S
authors: Grosso
authors: Chiara
authors: C
authors: Pantaleoni
authors: Morena
authors: M
authors: Doz
authors: Maria Luisa
authors: ML
authors: Poch-Olivé
authors: Francesca
authors: F
authors: Rivieri
authors: Giovanni
authors: G
authors: Sorge
authors: Graziella
authors: G
authors: Simonte
authors: Francesca
authors: F
authors: Licata
authors: Luigi
authors: L
authors: Tarani
authors: Emanuela
authors: E
authors: Terazzi
authors: Laura
authors: L
authors: Mazzanti
authors: Paola
authors: P
authors: Cerruti Mainardi
authors: Antonella
authors: A
authors: Boni
authors: Francesca
authors: F
authors: Faravelli
authors: Marina
authors: M
authors: Grasso
authors: Paolo
authors: P
authors: Bianchi
authors: Marcella
authors: M
authors: Zollino
authors: Emilio
authors: E
authors: Franzoni
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D019066:Facies; D005260:Female; D006627:Hirschsprung Disease / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008831:Microcephaly / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D014635:Valproic Acid / Q000627:therapeutic use; D055815:Young Adult; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D000927:Anticonvulsants; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D014635:Valproic Acid