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Death in adults with Prader-Willi syndrome may be correlated with maternal uniparental disomy
  1. A Smith1,
  2. G Loughnan2,
  3. K Steinbeck2,3
  1. 1Department of Cytogenetics, New Children’s Hospital, Westmead, Sydney, Australia
  2. 2Obesity and Metabolism Department, Royal Prince Alfred Hospital, Sydney, Australia
  3. 3University of Sydney, Australia
  1. Correspondence to:
 Dr A Smith, Department of Cytogenetics, Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia; 

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Prader-Willi syndrome (PWS) is a disorder comprising severe neonatal hypotonia, hypogonadism, gross obesity, short stature, small hands and feet, mental handicap, a characteristic facial appearance (almond shaped eyes, thin downturned upper lip, and a narrow bitemporal diameter), nasal, inarticulate speech, and a particular personality profile.1,2 Prader-Willi syndrome has a biphasic course. Initially there is severe neonatal hypotonia, difficulty in feeding, and failure to thrive, usually persisting for 12 months. This is followed by weight gain, and if unchecked obesity is well developed by 6 years of age.1,2 The gain in weight is primarily attributable to a hypothalamic defect resulting in an insatiable appetite and hyperphagia,3,4 but a lowered metabolic rate and lack of exercise owing to continuing hypotonia contribute.5 The patients have a food obsession with a rather specific food related behavioural phenotype, which includes foraging for food, stealing food, and eating inedibles.1,3

The clinical diagnosis of PWS can now be confirmed by accurate genetic testing. Methylation testing makes a definitive diagnosis in about 99% of patients, but will not define the genetic mechanism. Further simple DNA studies of the chromosome 15 (q11-q13) region will do this. These include fluorescence in situ hybridisation (FISH) to check for deletion and DNA polymorphisms for maternal uniparental disomy (UPD).6 A patient with a positive methylation result who is non-deleted and non-disomic has an imprinting defect (ID).7 The commonest genetic mechanism is paternal deletion of the imprinted region (about 75% of patients), followed by UPD in 24% and about 1% have an ID for this region.6,7

Key points

  • Prader-Willi syndrome (PWS) in adulthood in difficult to manage. We present our findings in 36 adults, seen at a multidisciplinary PWS clinic in a major Sydney teaching hospital over a 10 year period. …

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