Death in adults with Prader-Willi syndrome may be correlated with maternal uniparental disomy.

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. 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. 2 The gain in weight is primarily attributable to a hypothalamic defect resulting in an insatiable appetite and hyperphagia, 4 but a lowered metabolic rate and lack of exercise owing to continuing hypotonia contribute. The patients have a food obsession with a rather specific food related behavioural phenotype, which includes foraging for food, stealing food, and eating inedibles. 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). A patient with a positive methylation result who is non-deleted and non-disomic has an imprinting defect (ID). 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. 7 Adults with PWS are cared for in various ways throughout the community. 8 9 Cohorts of adults with PWS seen at clinics in the past found that morbid obesity was usual. 8 A recent study from the United Kingdom has confirmed a continuing high morbidity, despite better early diagnosis, knowledge, and management of PWS. This morbidity among adults is largely the result of complications associated with obesity, such as diabetes (mainly type 2), sleep apnoea, respiratory arrest, peripheral circulatory stagnation, slow healing of skin lesions, and osteoporosis, 10 11 but the hypotonia, which continues into adult life, contributes (for example, scoliosis, kyphosis, lack of exercise). Psychological problems are a cause of major concern to families, reported in 5%–15% of adult patients, and range from obsessive skin picking to overt cyclical psychosis. Hypothalamic insufficiency contributes to hypogonadism, temperature instability, low activity levels, and low metabolic rate, further affecting morbidity. A mortality rate for PWS has not been established by prospective studies. A retrospective prevalence population study in the United Kingdom estimated a mean mortality rate of 3% a year across all ages and 7% a year in those over 30 years of age. We present our findings in a cohort of adults with PWS consistently attending a multidisciplinary PWS clinic over the 10 year period 1991–2001. Our review was conducted to assess outcome data for adult patients and to look for possible future interventions which might improve clinical management.