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Aplicação dos critérios de diagnóstico de síndrome de Angelman actualizados aos doentes da consulta de neuropediatria

Research output: Contribution to journalArticle

Cristina Dias, Manuela Santos, Adriana Ribeiro, Inês Carrilho, Margarida Reis Lima, Clara Barbot, Rui Chorão

Original languagePortuguese
Pages (from-to)10-17
Number of pages8
JournalSinapse
Volume7
Issue number1
Publication statusPublished - 1 May 2007

King's Authors

Abstract

Introduction: Angelman Syndrome is a genetic disorder characterized by mental retardation, severe language deficit, movement disorder, EEG abnormalities (with or without seizures) and distinctive behavior. AS can be caused by different molecular mechanisms that lead to loss of maternal contribution of the 15q11.2-q13 chromosomal region; most cases are caused by deletion of the maternal allele or paternal uniparental disomy and in 10% they are due to point mutations in the UBE3A gene. In 10 to 15% of patients, genetic analysis is negative, which does not exclude the clinical diagnosis. In those patients with a 15q deletion a more severe presentation, with difficult to treat epilepsy has been described. Recently, the diagnostic criteria were updated (Williams et al, 2006). Objectives: The aim of this study was to review the patients with Angelman Syndrome followed at the Pediatric Neurology Department of our Hospital according to the updated diagnostic criteria, to ascertain a genotype-phenotype correlation and to review the literature. Methods: Fifteen patients were selected from the Pediatric Neurology database with a clinical diagnosis of AS; they were reassessed according to the updated diagnostic criteria for AS and their EEGs were reevaluated. All had southern blot or MSP-PCR analysis performed to detect deletion and/or uniparental disomy of the 15q11.2-q13 region. In one patient mutation analysis of the UBE3A gene was performed. Results: Three patients were excluded for not fulfilling the diagnostic criteria and one who was no longer followed and had insufficient data. Eleven patients fulfilled the updated diagnostic criteria. Of these, seven had a deletion or uniparental disomy of the 15q11.2-q13 region. In two patients no abnormality was found by southern blot; mutation analysis of the UBE3A gene was performed in one of these, but no point mutations were detected. All patients had abnormal EEG recordings. The most frequent pattern was posterior high-amplitude slow wave discharges with mixed spikes. Discussion and Conclusions: The diagnostic technique most frequently used (southern blot), could not discriminate the presence of a deletion or uniparental disomy in two patients, not allowing a genotype-phenotye correlation. The use of the updated diagnostic criteria supported the previous diagnosis in 11 patients. These criteria should be used for clinical evaluation prior to the request for genetic analysis. Even so, in some patients with a clinical diagnosis it is not yet possible to confirm the genetic disorder.

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