Epilepsy in Mowat–Wilson syndrome: Delineation of the electroclinical phenotype
- 15 January 2013
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 161 (2), 273-284
- https://doi.org/10.1002/ajmg.a.35717
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.Keywords
This publication has 24 references indexed in Scilit:
- Spectrum of epilepsy and electroencephalogram patterns in Wolf–Hirschhorn syndrome: experience with 87 patientsDevelopmental Medicine and Child Neurology, 2009
- Mowat–Wilson syndrome: Facial phenotype changing with age: Study of 19 Italian patients and review of the literatureAmerican Journal of Medical Genetics Part A, 2009
- Mowat–Wilson syndrome: an underdiagnosed syndrome?Clinical Genetics, 2008
- Spectrum of epilepsy in terminal 1p36 deletion syndromeEpilepsia, 2007
- Mowat-Wilson syndromeOrphanet Journal of Rare Diseases, 2007
- Clinical features and management issues in Mowat–Wilson syndromeAmerican Journal of Medical Genetics Part A, 2006
- Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the “Mowat–Wilson” syndromeNeurobiology of Disease, 2004
- Mowat-Wilson syndrome and mutation in the zinc finger homeo box 1B gene: a well defined clinical entityJournal of Medical Genetics, 2004
- Hirschsprung disease, mental retardation, characteristic facial features, and mutation in the gene ZFHX1B (SIP1): Confirmation of the Mowat‐Wilson syndromeAmerican Journal of Medical Genetics Part A, 2002
- Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung diseaseHuman Molecular Genetics, 2001