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Brescia, Italy

Capovilla G.,Epilepsy Center | Beccaria F.,Epilepsy Center | Bianchi A.,Epilepsy Center | Canevini M.P.,University of Milan | And 9 more authors.
Brain and Development | Year: 2011

Purpose: To describe the EEG pattern of seizures in patients with benign childhood epilepsy with centro-temporal spikes (BCECTS). Methods: The clinical and EEG data of 701 BCECTS patients with at least a 3. years follow-up were reviewed from 10 epilepsy centers. Results: Thirty-four seizures were recorded in 30 patients. Four different ictal EEG patterns (A-D) were identified. The most frequent (pattern A) was characterized by low voltage activity of fast rhythmic spikes, increasing in amplitude and decreasing in frequency, and occurred in 14 children. Pattern B (six patients) was constituted by a discharge of spikes intermixed with sharp waves increasing in frequency and amplitude. Pattern C (seven children) consisted of monomorphic theta which progressively formed a discharge increasing in amplitude and decreasing in frequency. Pattern D (5 children) was characterized by a initial focal depression of the electrical activity, followed by one of the three above described patterns. In 21 out of 28 children, the initial ictal pattern, altered from one pattern to another one. No clinical or EEG feature was predictive of a specific ictal pattern. Discussion: We failed to identify a unique ictal EEG pattern in our patients with BCECTS. The occurrence of per-ictal features, e.g., initial EEG depression or post-ictal slowing, is common and should not be interpreted with prejudice. Alteration of ictal EEG pattern from one to another is not in conflict with the diagnosis of BCECTS. © 2010 The Japanese Society of Child Neurology.

Artuso R.,University of Siena | Papa F.T.,University of Siena | Grillo E.,University of Siena | Mucciolo M.,University of Siena | And 11 more authors.
Journal of Human Genetics | Year: 2011

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies. © 2011 The Japan Society of Human Genetics All rights reserved.

Agostinelli S.,University of Chieti Pescara | Traverso M.,G Gaslini Institute | Accorsi P.,Child Neuropsychiatry | Beccaria F.,C Poma Hospital | And 22 more authors.
European Journal of Neurology | Year: 2013

Background and purposes: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). Methods: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. Results: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). Conclusions: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Bijlsma E.K.,Leiden University | Collins A.,Wessex Clinical Genetics Service | Papa F.T.,University of Siena | Tejada M.I.,Molecular Genetics Laboratory | And 26 more authors.
European Journal of Medical Genetics | Year: 2012

Duplications leading to functional disomy of chromosome Xq28, including MECP2 as the critical dosage-sensitive gene, are associated with a distinct clinical phenotype in males, characterized by severe mental retardation, infantile hypotonia, progressive neurologic impairment, recurrent infections, bladder dysfunction, and absent speech.Female patients with Xq duplications including MECP2 are rare. Only recently submicroscopic duplications of this region on Xq28 have been recognized in four females, and a triplication in a fifth, all in combination with random X-chromosome inactivation (XCI). Based on this small series, it was concluded that in females with MECP2 duplication and random XCI, the typical symptoms of affected boys are not present. We present clinical and molecular data on a series of five females with an Xq28 duplication including the MECP2 gene, both isolated and as the result of a translocation, and compare them with the previously reported cases of small duplications in females. The collected data indicate that the associated phenotype in females is distinct from males with similar duplications, but the clinical effects may be as severe as seen in males. © 2012 Elsevier Masson SAS.

Mencarelli M.A.,University of Siena | Tassini M.,University of Siena | Pollazzon M.,University of Siena | Vivi A.,University of Siena | And 10 more authors.
American Journal of Medical Genetics, Part A | Year: 2011

Creatine deficiency syndrome due to mutations in X-linked SLC6A8 gene results in nonspecific intellectual disability (ID). Diagnosis cannot be established on clinical grounds and is often based on the assessment of brain creatine levels by magnetic resonance spectroscopy (MRS). Considering high costs of MRS and necessity of sedation, this technique cannot be used as a first level-screening test. Likewise, gene test analysis is time consuming and not easily accessible to all laboratories. In this article feasibility of urine analysis (creatine/creatinine (Cr/Crn) ratio) performed by nuclear magnetic resonance (NMR) as a first level-screening test is explored. Before running a systematic selection of cases a preliminary study for further molecular analysis is shown. NMR urine spectra (n=1,347) of male patients with an ID without a clinically recognizable syndrome were measured. On the basis of abnormal Cr/Crn ratio, three patients with the highest values were selected for molecular analysis. A confirmatory second urine test was positive in two patients and diagnosis was further confirmed by a decreased brain creatine level and by SLC6A8 gene analysis. A de novo mutation was identified in one. Another patient inherited a novel mutation from the mother who also has a mild ID. A repeat urine test was negative in the third patient and accordingly creatine level in the brain and SLC6A8 gene analysis both gave a normal result. We conclude that Cr/Crn ratio measured by NMR for male patients represents a rapid and useful first level screening test preceding molecular analysis. © 2011 Wiley-Liss, Inc.

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