[Genetic and clinical diagnosis of Angelman syndrome. Case Reviews]

Angelman syndrome is characterised by mental retardation, epilepsy, speech impairment, facial dysmorphism and a characteristic behavioural phenotype. Diagnostic clinical criteria have been defined by consensus since 1995. It is caused by deficiency or inactivation of the UB3A gene. There is a percentage of cases which satisfy these clinical features but have negative genetic testing. We consider it necessary to analyse the patient characteristics and possible phenotype-genotype correlations.

All cases which were treated between 1981 and 2007 in a neurology unit and fulfilled the clinical criteria were included. Genetic diagnosis was made by methylation testing and fluorescent in situ hybridization.

Thirteen patients were studied, nine with positive genetic testing and four with negative testing who completed the clinical criteria. The average age at diagnosis was 37 months. Eleven cases showed acquired microcephaly. Flat occiput, mouth and maxillary malformations, hypopigmentation, a happy appearance and hyperactivity were practically constant characteristics. Speech and walking ability were the areas which showed most deficit. Twelve cases had epilepsy. Three of the cases with normal genetic testing showed less microcephaly and better psychomotor development, particularly in walking ability.

The phenotypical characteristics of the syndrome should be known before requesting specific genetic testing and to make a diagnosis even in cases with negative genetic. The phenotype characteristics that describe Angelman syndrome were verified. Deletion cases had a worse outcome.