Cardiovascular autonomic dysfunction and sleep abnormalities in children with Prader-Willi syndrome.

PURPOSE: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental condition characterized by cognitive disabilities, behavioral problems, hypothalamic dysfunction with obesity, and sleep disorders. A few studies have reported autonomic nervous system dysfunction. Our aim was to investigate dysautonomia by combining sleep studies and standard autonomic testing in regularly followed children with PWS.

METHODS

In this retrospective study, heart rate variability was analyzed during each sleep stage (polysomnography) using time and frequency domains in PWS children (N = 37) compared with age-matched controls (N = 20). Cardiovascular autonomic testing (Ewing tests) and sweating assessment (electrochemical skin conductance) were also performed in patients over 6 years (N = 23).

RESULTS

Autonomic testing: Heart rate changes with active standing and with deep breathing were impaired in 47% and 22% of the children, respectively. Asymptomatic orthostatic hypotension (OH) was found in 26%. Baroreflex sensitivity in supine position was in normal range (14.1 ± 6.7 ms/mmHg). Electrochemical skin conductance was normal. Sleep study: 46% of the children with PWS had obstructive sleep apnea and 24% had central sleep apnea. None of these events were observed in the control group. Mean R-R and time domain heart rate variability parameters were significantly lower compared with controls in N2 and Rapid Eye Movement (REM) sleep stages. Narcoleptic-like phenotype was found in 47% associated with lower low-frequency (LF) power (sympathetic index) in REM sleep.

CONCLUSION

Our study confirms a decreased vagal modulation during both wakefulness and sleep in children with PWS. OH in some patients suggests a sympathetic dysfunction. These changes may contribute to the increased cardiovascular risk in PWS.