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.