Abstract
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.
Highlights
Angelman syndrome (AS) is a neuro-behavioural, genetically determined condition, described in 1965 by Dr Harry Angelman, a British paediatrician[1].Patients are widely known for their behavioural and motor pattern well defined as "happy puppet", this denomination is avoided because of the possible derision meaning to the family
We are aware of another condition, named Pitt-Hopkins syndrome with similar clinical signs and we suggest to verify this possible diagnosis in AS and Rett syndrome (RTT) cases without a molecular confirmation
Seizures are observed in the great majority of AS patients, may have a early onset and are often refractory to treatment
Summary
Angelman syndrome (AS) is a neuro-behavioural, genetically determined condition, described in 1965 by Dr Harry Angelman, a British paediatrician[1]. Valente et al[27] described as "hypsharrhythmiclike variants" the observed EEG tracing characterized by runs of high amplitude asynchronous delta activity associated with multifocal spikes and sharp waves of moderate amplitude This pattern, resembling hypsharrhythmmia showed a predominance of slow waves over the epileptiform discharges. Dion et al[34] evaluated Lamotrigine(LMT) efficacy in 5 patients with different types of seizures (myoclonic, tonic clonic, atypical absences) unresponsive to other drugs (VPA, Benzodiazepines, phenytoine, carbamazepine and topiramate) obtaining a good control in 3 of Figure 2 EEG at different ages. The EEG pattern changed showing a very slow background activity mixed with multifocal spikes (Fig. 2b) Besides these data, our personal experience suggests us the importance of a early diagnosis in view of a possible familial recurrence. The impaired development of the noradrenergic neurons pathway might cause abnormal respiratory network inside the brain
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