This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Familial dysautonomia (FD), i.e. the hereditary sensory and autonomic neuropathy (HSAN) type III, or Riley-Day-Syndrome, is a rare autosomal recessive disorder with extensive central and peripheral autonomic perturbations, accounting for cardio- and cerebrovascular dysregulation as well as compromised respiratory control. Although the prognosis for FD has markedly improved with better treatment, patients with FD still succumb to severe hypertensive dysautonomic crises and sudden unexplained death. Clinically, such events frequently occur during sleep or arousal from sleep, particularly in early morning hours or after having taken a nap. It is still unclear why and how the crises and sudden fatalities are linked to the sleep cycle in FD. However, dysfunction of several mechanisms, such as baroreflexes and chemoreflexes that should assure respiratory and cardiovascular adaptation to autonomic changes occurring at various NREM phases, during REM sleep and arousal, has been documented in FD. Therefore, we hypothesize that inadequate responses to those changes during sleep and arousal phases are a major cause of life threatening cardiovascular emergencies in FD patients. We assume that a detailed evaluation of cardiovascular autonomic function during sleep and wakefulness will better elucidate the mechanisms of those emergencies in FD and will possibly allow for therapeutical interventions mitigating some of the sleep related cardiovascular instability in FD patients.
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