Unexpected Angelman syndrome molecular defect in a girl displaying clinical features of Prader-Willi syndrome

Editor— Prader-Willi syndrome (PWS)1and Angelman syndrome (AS)2 are clinically distinct neurobehavioural disorders both resulting from altered expression of specific imprinted genes located in the 15q11q13 chromosomal region. PWS is usually caused by a deletion in the paternally inherited chromosome 15 or by maternal uniparental disomy (UPD) of chromosome 15, whereas maternal deletion or paternal UPD is responsible for AS.3 4 AS patients exhibit severe mental retardation with absence of speech, frequent and inappropriate laughter, ataxic gait with raised arms, and a frequent history of seizures. Most patients have a typical face with a wide open mouth, protruding tongue, and prominent chin.5 Clinical history and physical examination are different in patients with PWS, who have neonatal hypotonia almost invariably associated with poor sucking requiring nasogastric feeding, hypogonadism, short stature, mild to moderate mental retardation, and childhood onset obesity owing to hyperphagia beginning between 1 and 6 years.6 However, although all these clinical characteristics are well defined, molecular confirmation is recommended considering that other diseases share identical clinical features, for example fragile X syndrome and PWS,3 7 8 or Rett syndrome and ATR-X syndrome and AS.5 9 The molecular diagnosis of PWS and AS is based on the analysis of the differential parental specific DNA methylation imprint within the 15q11-q13 chromosomal region. This investigation is currently …