Angelman syndrome (AS) is a neuro-behavioural, genetically determined condition, characterized by ataxic jerky movements, happy sociable disposition and unprovoked bouts of laughter in association with seizures, learning disabilities and language impairment. Most of the cases are hardly diagnosed during infancy as jerky movements, the cardinal sign, appear later in childhood.AS is caused by a variety of genetic mechanisms involving the 15q 11-13 chromosome. About 70% of cases are due to a "de novo" interstitial deletion in the long arm region, arising on the maternally inherited chromosome. The diagnosis is confirmed by methylation test or by mutation analysis of UBE3A gene. The deletion phenotype is generally linked to a more severe clinical picture in that 95% of patients manifest more severe seizures, severe mental and motor retardation, dysmorphic features and microcephaly.The pathogenesis of epilepsy in AS is still not fully understood. The presence in the commonly deleted region of a cluster of genes coding for 3 subunits of the GABAa receptor complex has lead to the hypothesis that GABA neurotransmission is involved.Epilepsy, often severe and hard to control, is present in 85% of patients within the first three years of life, although less than 25% develop seizures during the first year. It was observed that febrile seizures often precede the diagnosis. Most frequent types are atypical absences, generalized tonic-clonic, atonic or myoclonic seizures, with multiple seizure types occurring in 50% of deleted patients. There is still some doubt about the association with West syndrome.The EEG abnormalities are not themselves pathognomonic of AS and both background activity and epileptic discharges vary even in the same patient with time. Nevertheless, the existence of some suggestive patterns should facilitate the early diagnosis allowing the correct genetic counselling for the family. Some drugs seems to act better than others, Valproate, ethosuximide and clonazepam giving the best results.

Objectives: Atomoxetine is commonly used to treat attention-deficit hyperactivity disorder (ADHD) in children with a broad range of cognitive abilities. We examined the association between level of cognitive functioning as determined by IQ and clinical response during treatment with atomoxetine. Methods: The records of all the children and adolescents treated with atomoxetine at a university clinic in Catania, Italy, over a 3-year period were examined. A total of 55 clinically referred children and adolescents (aged 5-15 years, 53 males) with ADHD were treated with atomoxetine (10-110 mg/day; mean: 1.28 mg/kg/day) for a period ranging from 2 to 168 weeks (mean: 57.3 -SD 39.4, median: 56). The IQ was assessed as part of the diagnostic evaluation prior to starting treatment. During treatment, clinical outcome was rated on the Clinical Global Impression-Improvement (CGI-I) and CGI-Severity (CGI-S) scales. Results: The IQ ranged from 43 to 117 (mean: 80.6 -SD 18.6, median: 84). The IQ and final CGI-I scores were negatively correlated (r = -0.68; p < 0.01). Children and adolescents with an IQ <85 were less likely to be responders (defined as a final CGI-I score of 1 or 2) than children and adolescents with an IQ ‡85 (20.71% vs 76.9%; p < 0.001). None of the patients discontinued atomoxetine due to adverse effects, while treatment was discontinued in 20 subjects due to a lack of efficacy or ambivalence of parents about pharmacological treatment.Conclusions: Atomoxetine appears to be less effective in children and adolescents with an IQ <85 than in children and adolescents in the average range of cognitive functioning. This difference is not accounted for by differences in the severity of ADHD symptoms, co-morbidity or reduced tolerability to the medication. These findings suggest that, in order to be fully informative, clinical trials of medications for ADHD should also include children and adolescents functioning in the borderline and cognitive disability range.

The authors previously reported on the initial manifestations in a set of female twins, who presented soon after birth with bath-induced paroxysmal events each time they were immersed in a warm water bath. These episodes progressively ceased by the age of 36 months, replaced by paroxysmal episodes of alternating hemiplegia unrelated to water immersion. By age 4 years, the twins developed the classic features of alternating hemiplegia of childhood. Clinical outcomes at the age of 11 years are now reported. Standard and video-electroencephalograms showed a large, slow background activity followed by lower amplitude waves without focal abnormalities or other abnormal findings. This represents the first report on (a) alternating hemiplegia of childhood started with bath-induced paroxysmal episodes; (b) this condition in monozygotic twins; and (c) an 11-year follow-up study in which the twins continue to experience episodes of alternating hemiplegia in the setting of baseline cognitive impairment without epileptic episodes.

SummaryWe report on monozygotic twins with neonatal onset of daily reflex seizures triggered by hot water. Video record during the hot water bathing showed clinical signs consistent with a reflex seizure. The numbers of episodes were markedly reduced when the mother began bathing the children with reduced temperature bath water. At the age of 20 months, the twins developed episodes of paroxysmal disturbances including alternating hemiplegia. These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia.

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