Assessment of sleep and breathing in adults with Prader-Willi syndrome: a case control series

Objectives: Prader-Willi syndrome (PWS) is a genetic disorder (linked to chromosome 15q11-13) characterized by hypotonia and developmental delay, hyperphagia and obesity, hypersomnia and abnormal sleep, and behavioral problems. Such patients may also be at increased risk of obstructive sleep apnea (OSA), although whether this risk is explained by known risk factors has not previously been directly tested. Our aim was to compare sleep and breathing in an older group of patients with Prader-Willi syndrome with a control group - matched on the basis of age, sex, and body mass index (BMI) - in order to determine which specific features are not explained by these known confounders. Methods: Consecutive patients with PWS attending the PWS clinic at Royal Prince Alfred Hospital Sydney, Australia, were recruited. Age-, sex-, and BMI-matched controls were selected from the Sleep Investigation Unit at Royal Prince Alfred Hospital, and polysomnography-derived sleep and other parameters were compared across the groups. Results: Nineteen subjects with PWS (14 males) were included in the study. Eighteen (95 %) had a total respiratory disturbance index (TRDI) of greater than 5 events per hour, with 4 (21%) having severe obstructive sleep apnea (TRDI ≥ 30 events/hour) and 9 (47%) having evidence of obesity hypoventilation syndrome. Patients with PWS, as compared with the control group, had evidence of more nocturnal hypoxemia, with lower oxyhemoglobin saturations and percentages of sleep time at less than 80% oxyhemoglobin saturation (all p values < 0.05). There were no significant differences in sleep architecture; however, there was a reduction in rapid eye movement latency seen in the PWS group (p < 0.05). Serum leptin was higher than the reference range in the PWS group but was not measured in the control group. Conclusion: Patients with PWS drawn from an adult and adolescent PWS clinic have a high rate of sleep-disordered breathing. There is evidence that patients with PWS may have more nocturnal hypoventilation than a well-matched control group. These data suggest that the chromosome region 15q11-13 may be involved in some aspects of the regulation of breathing, although whether putative molecular mechanisms act directly or indirectly will require further investigation.