In patients with Familial Dysautonomia (FD), also called Riley-Day syndrome or hereditary sensory and autonomic neuropathy type III, compromised baroreflex function seems to account for severe orthostatic hypotension without reflex tachycardia. Moreover, FD patients have prominent respiratory abnormalities such as breath-holding or sleep apneas, probably due to impaired chemoreflex sensitivity. Most importantly, there is a high risk of unexplained sudden death in FD patients (1). Somers et al. suggested that impaired baroreflex function may predispose to excessive autonomic responses to apnea induced chemoreflex stimulation; responses may comprise non-buffered bradyarrhythmias and sympathetic activation leading to cardiovascular catastrophe and sudden death (2).

We have assessed whether FD patients have impaired cardiovascular responses to baroreflex activation and to hypoxic and hypercapnic chemoreflex stimulation (3, 4). In 21 FD patients and 22 controls, we performed 3 minutes of passive head-up tilt (HUT) and baroreceptor stimulation using sinusoidal neck suction (NS; 0 to -30 mm Hg; 0.1 Hz [LF] and 0.2 Hz [HF]). During NS, participants kept respiration at 15 breaths/minute. We recorded RR-intervals (RRI), blood pressure (BP), and respiration and assessed NS induced changes in RRI and BP by spectral analysis (3). Moreover, we assessed responses of ventilation, end-tidal carbon dioxide (CO2-et), oxygen saturation, RRIs, and BP to progressive isocapnic hypoxia, progressive hyperoxic hypercapnia, and during recovery from moderate hyperventilation (4). In FD patients, HUT induced orthostatic hypotension without compensatory tachycardia. Only controls, but not FD patients, had augmented LF powers of RRI and BP with LF-NS and increased HF powers of RRI with HF-NS (3). In the FD patients, hyperoxic hypercapnia generated normal cardiovascular and ventilatory responses while progressive hypoxia induced an only blunted increase in ventilation and paradoxical RRI- and BP-decreases. Hyperventilation caused prolonged apneas with prominent oxygen desaturation, BP decrease, and RRI increase (4). FD patients have baroreflex dysfunction with insufficient sympathetic vasomotor responses and insufficient cardiac sympathetic and parasympathetic responses to stimulation; the baroreflex dysfunction likely accounts for abnormal BP control with supine hypertension and orthostatic hypotension as well as bradyarrhythmias (3). In FD patients, hypoxia induces central depression with hypotension, bradycardia, and hypoventilation. The combined dysfunction of the baro- and chemoreflexes may account for the increased risk of sudden death in FD patients, possibly to due bradycardia and continued respiratory arrest during hyperventilation or hypoxia (4).

References: 

1. Axelrod FB & Hilz MJ. (2000). Familial dysautonomia. In: Appenzeller O, Editor. Handbook of Clinical Neurology. The Autonomic Nervous System. Part II - Dysfunctions. Amsterdam: Elsevier. p 143–160).

2. Somers VK et al (1992). Clin Auton Res, 2: 171–6.

3. Stemper B et al. (2004). Neurology, 63:1427–31.

4. Bernardi L et al. (2003). Am J Respir Crit Care Med, 167: 141–9.