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Summary Purpose To investigate the electroclinical features and the outcome of patients with typical absences starting before the 3 years of life. Methods We reviewed the clinical data of patients with absences started before 3 years observed over a 15-year period. Mutation analysis of SLC2A1 (GLUT-1) gene was performed when possible. Their clinical features were compared with those of subjects with a diagnosis of childhood absence epilepsy (CAE). Results Among 33 children with absence epilepsy starting before 3 years of life, there were 20 boys and 13 girls. Mean seizure onset was at 28.0±8.3 (range: 8–36) months of life. Two children displayed borderline intellectual functioning at long-term follow-up. Twenty-eight (85%) patients showed excellent response to therapy. Three subjects evolved into a different form of idiopathic generalized epilepsy (IGE). No SLC2A1 mutation was identified in 20 (60.6%) patients tested. The main clinical features of patients with early-onset absences did not differ from those of CAE except for increased prevalence of males ( p =0.002) and longer treatment duration ( p =0.001) in the former. Conclusions Strong similarities in the electroclinical features and outcome between children with early-onset absences and those with CAE support the view that these conditions are part of the wide spectrum of IGE.

Background and purposes: To determine the prevalence of SLC2A1 mutations inchildren with early-onset absence epilepsy (EOAE) and to investigate whether therewere differences in demographic and electroclinical data between patients whobecame seizure-free with anti-epileptic drug (AED) monotherapy (group I) andthose who needed add-on treatment of a second AED (group II).Methods: We reviewed children with EOAE attended different Italian epilepsy cen-ters. All participants had onset of absence seizures within the first 3 years of life butotherwise conformed to a strict definition of childhood absence epilepsy. Mutationanalysis of SLC2A1 was performed in each patient.Results: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusioncriteria. No mutation in SLC2A1 was found. There were no statistical differencesbetween the two groups with regard to F/M ratio, age at onset of EOAE, early his-tory 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, failedwithdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month fol-low-up EEG data. Mean duration of seizures/active epilepsy was significantlyshorter in group I than in group II (P = 0.008).Conclusions: We demonstrate that in a large series of children with rigorous diag-nosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration ofseizures/active epilepsy, no significant differences in demographic and electroclinicalaspects are observed between children with EOAE who responded well to AEDmonotherapy and those who became seizure-free with add-on treatment of a secondAED.

Summary Purpose To investigate whether patients with typical absence seizures (TAS) starting in the first 3 years of life, conformed to Panayiotopoulos's definition of childhood absence epilepsy (CAE), show different electroclinical course than those not fulfilling CAE criteria. Methods In this multicenter retrospective study, we choose a fixed duration follow-up of 36 months to examine the electroclinical course of epilepsy in all children with TAS starting before 3 years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were classified as having pure early onset absence epilepsy (P-EOAE), whereas those who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients were further stratified according to the number of antiepileptic drugs taken to obtain initial seizure control (mono-, bi-, and tritherapy). Key Findings Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030) and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n = 77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE. Among patients with NP-EOAE, those receiving tritherapy showed increased risk of structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p = 0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had 2.134 the odds of having relapse during the follow-up compare to those with P-EOAE. Significance Children with early onset TAS who did meet Panayiotopoulos's criteria showed a favorable course of epilepsy, whereas patients not fulfilling Panayiotopoulos's criteria showed increased risk of relapse at long-term follow-up.

The widespread use of Array Comparative Genomic Hybridization (aCGH) technology has enabled the identification of several syndromes associated with copy number variants (CNVs) including the 17q21.31 microdeletion. The 17q21.31 microdeletion syndrome, also known as Koolen-de Vries syndrome, was first described in 2006 in individuals with intellectual disabilities and organ abnormalities. We report the clinical, instrumental, cytogenetic and molecular investigations of a boy admitted for epilepsy and intellectual disabilities. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis by using aCGH. We identified a de novo microdeletion on chromosome 17q21.31, compatible with Koolen-de Vries syndrome. Our case shares some of the typical characteristics of the syndrome already described by other authors: delayed psychomotor development, primarily affecting the expressive language, dysmorphic facial features, and epilepsy. However the clinical outcome was not severe as the intellectual disabilities were moderate with good adaptive and functional behaviour. Epilepsy was easily controlled by a single drug, and he never needed surgery for organ abnormalities. ! 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

15q.13.3 microdeletion has been described in a variety of neurodevelopmental disorders. Epilepsy appears to be a common feature and, specifically, the 15q13.3 microdeletion is found in about 1% of patients with idiopathic generalized epilepsy. Recently, absence seizures with intellectual disability (ID) have been reported in patients carrying this mutation. We describe two families in which several affected members carry a 15q13.3 microdeletion in a pattern suggestive of autosomal dominant inheritance. Their phenotype includes mainly absence epilepsy and mild ID, suggesting only similarities with genetic/idiopathic generalized epilepsies but not typical features. The importance of studying such families is crucial to broaden the phenotype and understand the long-term outcome of patients with this condition.

Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. Conclusions Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.

West syndrome (WS) is characterized by infantile-onset flexor and extensor spasms, an EEG pattern of a high amplitude with asynchronous activity of spikes and theta/delta waves (hypsarrhythmia), and impaired psychomotor development.1 In about 70%–80% of the children, WS develops as a consequence of metabolic disorders or brain lesions, but in many cases the etiology is unknown.2 ### Methods. See also appendices e-1 (Methods) and e-2 (case descriptions) on the Neurology ® Web site at www.neurology.org. We screened by high-resolution comparative genomic hybridization (array-CGH) 38 (20 male, 18 female) consecutively collected patients with WS of unknown etiology (table e-1). Diagnosis was based on 1) absence of prenatal or postnatal etiologic factors, 2) normal development and absence of neurologic abnormalities before the onset, and 3) normal laboratory and MRI findings at onset.1 Patients showing dysmorphisms or other birth defects were excluded. Mutations in ARX and CDKL5 / STK9 genes2 were excluded in all the patients. The Ethics Committees of involved centers approved the study and an informed consent was signed by the parents. …

Summary: Purpose: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. Methods: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. Results: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. Conclusions: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.

SummaryBackgroundDiagnosing asthma cannot be always easy. It is important to consider the validity of the diagnostic tests, and/or how much more commonly they are positive in patients with asthma compared to healthy subjects and, particularly, to patients with asthma-like symptoms.ObjectiveTo evaluate the validity of diagnostic tests for asthma, in terms of sensitivity, specificity, positive and negative predictive values, in patients with bronchial asthma compared to patients affected by gastro-oesophageal reflux disease (GERD) with asthma-like symptoms, and healthy control subjects without asthma and gastro-oesophageal reflux (GER).DesignSingle-center, cross-sectional, observational study.PatientsWe studied 60 patients with mild asthma, 30 patients with GERD and asthma-like symptoms and 25 healthy control subjects.MeasurementsWe measured provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in 1s (MCh PC20/FEV1), the amplitude percent mean of peak expiratory flow (A%M of PEF), derived from twice-daily readings for >2 weeks, the FEV1/forced vital capacity (FEV1/FVC) ratio, the eosinophil count in blood and in induced sputum and the serum eosinophil cationic protein (ECP) levels.ResultsFEV1/FVC ratio, A%M of PEF, blood eosinophils counts and serum ECP levels were less sensitive and specific when the reference population was composed of patients with asthma-like symptoms by GER. While, MCh PC20/FEV1 and induced sputum eosinophils count were the most sensitive (both 90%) and specific (89% and 92%, respectively) tests.ConclusionOur findings demonstrate that MCh PC20/FEV1 and the induced sputum eosinophil count are the most useful objective tests in patients with mild asthma. All patients with asthma presented both an MCh PC20/FEV1 1%.