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.

Mowat-Wilson syndrome: neurological and molecular study in seven patients

“…In our group, similarly to the literature, the first seizure occurred at a mean age of 1 year and 8 months, and in three patients, it occurred within the first year of life, in contrast with the observations of Cordelli et al, who rarely observed the start of epilepsy in the first year of life 19 . A fever-triggered seizure, in most cases, is the first seizure and is frequent 19 ; fever-triggered seizure was observed in four patients of our patients, at a median age of 1 year and 2 months. Nonfebrile seizures typically started usually afterwards, with a mean age of onset of 2 years and 10 months (varying from 9 months to 5 years).…”

“…Nonfebrile seizures typically started usually afterwards, with a mean age of onset of 2 years and 10 months (varying from 9 months to 5 years). Another seizure characteristic was apparent activation during sleep, also observed in a previous study 19 . All of our patients presented frequent seizures during sleep, and two of them presented with exclusively sleep seizures.…”

“…All of our patients presented frequent seizures during sleep, and two of them presented with exclusively sleep seizures. In our group, all patients presented with focal seizures, and, unlike Cordelli et al 19 , atypical absence seizures were not observed. No specific EEG pattern or cortical area was observed in our patients, but in one patient in this series, activation of EEG abnormalities during sleep was observed, as described previously 19 .…”

Epilepsy in Mowat‐Wilson syndrome: Is it a matter of GABA?

“…We recently delineated the electroclinical phenotype of epilepsy in MWS. In these patients, epilepsy is usually characterized by frontal lobe and atypical absence seizures, often preceded by fevertriggered seizures; in addition, we observed an age-dependent electroencephalography (EEG) pattern with frequent diffuse frontal dominant spike and wave discharges during the awake state and a near to continuous spike and wave activity during slow sleep (Cordelli et al, 2013).…”

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

“…26 One of the major challenges posed by MWS is the recurrence of seizures. 27 In 2013 Cordelli et al 28 hypothesized that a distinct electroclinical phenotype featuring focal and atypical absence seizures (which are often preceded by febrile seizures) and age-dependent electroencephalogram changes can be detected in the majority of patients with MWS.…”