Sd Angelman

SÍNDROME DE ANGELMAN
ORIGINAL

Síndrome de Angelman: características físicas y fenotipo conductual
en 37 pacientes con diagnóstico genético confirmado
M. Galván-Manso a, J. Campistol a, E. Monros b, P. Póo a, A.M. Vernet a, M. Pineda a, A. Sans a,
J. Colomer a, J. Conill a, F.X. Sanmartí a
ANGELMAN SYNDROME: PHYSICAL CHARACTERISTICS AND BEHAVIOURAL PHENOTYPE
IN 37 PATIENTS WITH CONFIRMED GENETICDIAGNOSIS
Summary. Introduction. Angelman syndrome (AS) is characterised by mental retardation, ataxic gait, epilepsy, absence of
language and a special series of physical traits behavioural phenotype. Its incidence is estimated as one in every 20,000
individuals. On the basis of discoveries made in molecular biology, patients can be classified as belonging to five types: deletion,
paternaluniparental disomy (UPD), imprinting defects, mutation of the UBE3A ubiquitin-protein ligase gene and unidentified
mechanism (15%-20% of patients). Some studies report significant correlations between the phenotype and the genetic cause.
Patients and methods. We reviewed, retrospectively, 37 patients suffering from AS with a positive genetic study and who had been
controlled for at least two years inthe Neurological Service at the Hospital Sant Joan de Déu. Data was collected on physical
characteristics, behavioural phenotype, type of communication, sleep disorders and the medication they needed, as well as
epilepsy, start age, types of seizures, medication, schooling and social integration. Results. 87% of cases were due to de novo
deletion, 8% were caused by UPD, and 5% had their origins inimprinting defects. The average age of diagnosis was 6.5 years.
The sleep disorders present in 48% of the patients required medication in 67% of cases, and 95% presented epilepsy. The most
frequent seizures were myoclonic, tonic-clonic and atonic. The electroencephalogram (EEG) was the characteristic found in the
AS in 68%. The most effective treatment was afforded by valproate and clonazepam.Conclusions. As regards the phenotype, no
differences were found according to the genetic alteration. The most effective treatment for the sleep disorders was melatonin.
Epilepsy was an almost constant finding in our series, as was cognitive affectation. Lastly, it must be pointed out that educational
and socio-occupational integration is difficult for patients suffering from AS. [REV NEUROL 2002; 35:425-9]
Key words. Angelman syndrome. Behavioural phenotype. Epilepsy. Genetic diagnosis. Sleep disorders. Socio-occupational
integration.

INTRODUCCIÓN
En 1965, Harry Angelman informó de tres pacientes con unas
características fenotípicas y conductuales peculiares [1]. El síndrome de Angelman (SA) se caracteriza principalmente por retraso mental, marcha atáxica, epilepsia, ausencia de lenguaje,una serie de rasgos físicos y un fenotipo conductual especiales
(Tabla). Su incidencia estimada es de uno por cada 20.000 individuos [2].
Desde la primera descripción, se ha progresado mucho en la
definición de las características clínicas de los pacientes y en la
comprensión de los mecanismos genéticos del síndrome. Los
hallazgos indican que el SA está causado, en un elevado porcentaje de casos,por la ausencia de la contribución génica materna
de la región 15q11-13. La causa genética más común, presente en
un 70% de los pacientes, es una deleción de novo de origen materno de la región 15q11-13. Entre un 3 y un 5% de los pacientes
presentan una disomía uniparental paterna del cromosoma 15, y
en un 8% de los casos la causa es una mutación en el centro de
impronta. Sobre la base de loshallazgos de la biología molecular,
los pacientes pueden clasificarse en cinco formas: deleción, disomía uniparental paterna, defecto de impronta, mutación en el gen
de la proteína ligasa de ubiquitina E3 (UBE3A), mecanismo no

Recibido: 03.04.02. Aceptado tras revisión externa sin modificaciones: 05.06.02.
a

Servicio de Neurología. Unidad Integrada. Hospital Sant Joan de Déu-Hospital Clínic. b...