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Severe phenotype in Angelman syndrome resulting from paternal isochromosome 15
  1. D Poyatos1,
  2. M Guitart2,
  3. E Gabau2,
  4. C Brun3,
  5. M Mila4,
  6. J Vaquerizo5,
  7. M D Coll1
  1. 1Unidad de Biología Celular, Facultad de Ciencias, Departamento de Biología Celular, Fisiología e Inmunología, Universidad Autónoma de Barcelona, Bellaterra, Barcelona, Spain
  2. 2Servicio de Laboratorio, Genética, Servicio de Pediatria, Corporación Parc Taulì, Sabadell, Barcelona, Spain
  3. 3Facultad de Psicología, Universidad Autónoma de Barcelona, Bellaterra, Barcelona, Spain
  4. 4Hospital Clínico, Departamento de Genética, Barcelona
  5. 5Departamento de Pediatria, Hospital Materno-Infantil Universitario “Infanta Cristina”, Badajoz, Spain
  1. Correspondence to:
 Dr D Poyatos, Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Ciencias, Edificio C, Universidad Autónoma de Barcelona, 08913 Bellaterra, Barcelona, Spain;

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Angelman syndrome (AS) is a neurogenetic disorder with an occurrence of approximately 1/20 000 live births.1 Characteristic features include severe mental retardation, absence of speech, seizures, abnormal EEG, hyperactivity, happy disposition with unmotivated laughter, ataxia of gait, and physical anomalies such as microbrachycephaly, macrostomia, protruding tongue, and widely spaced teeth.2 The clinical diagnosis of AS is usually not suspected during the first years of life because the early features are non-specific and the diagnosis is usually made between the ages of 2 and 16. In adults, the clinical diagnosis is often difficult because some characteristics, such as hyperactive behaviour, bursts of laughter, seizures, and EEG pattern tend to improve with age.3 As a result, the frequency of AS is probably underestimated.

AS is caused by the functional absence of the maternal copy of 15q11-q13. This region is subject to genomic imprinting, whereby gene expression is dependent on the parent of origin.4 In about 70% of cases, it is caused by de novo maternal deletions in the 15q11-q13 region, in approximately 2-3% by paternal uniparental disomy (UPD) of chromosome 15, and in 3-5% by imprinting mutations. The remaining AS patients (20%) have biparental inheritance. Some of these cases result from intragenic mutations in the UBE3A gene.5,6 About 20% of AS families in the imprinting mutation and biparental inheritance groups have more than one affected relative.2,7,8

Prader-Willi syndrome (PWS) is located in the same region. This syndrome is caused by the functional absence of the paternal copy of 15q11-q13. PWS is a phenotypically distinct disorder from AS and is characterised by infantile hypotonia, hypogonadism, mild to moderate mental retardation, hyperphagia (leading to obesity), short stature, small hands and feet, and characteristic facial appearance.9 Some of these characteristics, such as hyperphagia and obesity, …

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