Search

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 (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617–623], ∼179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21–q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition. © 2009 Wiley-Liss, Inc.

Topiramate (TPM) is a new, effective and safe antiepileptic drug. TPM is also effective in treating a wide spectrum of conditions such as eating disorders and related anomalies, bulimia nervosa and other conditions in which serotonin (5-hydroxytryptamine, 5-HT) is involved pathogenetically. Plasma serotonin mainly derives from blood platelets, which represent a valid model of serotoninergic neurons. We measured plasma 5-HT levels in 12 children affected by epilepsy who underwent TPM therapy. Inclusion criteria were (i) age range 2–12 years, (ii) weight greater than 12 kg, (iii) no more than one antiepileptic drug used when TPM therapy was instituted, and (iv) a minimum study period of 3 months. After a mean period of 3 months of TPM treatment, a significant increase in mean plasma serotonin levels was observed with respect to the basal levels and those of a control group. There were no significant correlations between the changes in serotonin concentrations and the antiepileptic efficacy or doses of TPM used. TPM may influence serotonin metabolism in children affected by epilepsy. Further studies are needed to establish whether these serotonin plasma changes represent an epiphenomenon or indicate direct effects of TPM on the serotoninergic system.

Allopregnanolone belongs to a group of neuroactive steroid hormones, or neurosteroids, synthesized and acting within the brain and is as a potent endogenous positive modulator ofGABAA receptor complex. Administration of allopregnanolone protects rats against pentylentetrazol, bicuculline, kainic acid, and picrotoxin-induced seizures. We investigated serum allopregnanolone levels in children with active epilepsy at pubertal Tanner’s stage I (n = 52). Blood specimens were collected at least 12 h after a seizure (inter-ictal). In a subgroup of patients (n = 11), specimens were also collected within 30 min from a seizure attack (post-ictal). Healthy age-matched children (n = 18) served as controls. Serum allopregnanolone was measured by radioimmunoassay using a polyclonal antiserum. The inter-ictal serum allopregnanolone levels in the epileptic children were not statistically different from those detected in the control group, whereas post-ictal levels were significantly higher than the inter-ictal ones (P = 0.0001). In this subgroup of patients allopregnanolone levels decreased to the basal values during the following 12 h. Serum allopregnanolone levels may therefore reflect changes in neuronal excitability, and allopregnanolone appears to be a reliable circulating marker of epileptic seizures. It is possible that increased post-ictal serum levels of allopregnanolone may play a role in modulating neuronal excitability and may represent an endogenous mechanism of seizure control.