Abstract
Familial dysautonomia (Riley–Day syndrome, hereditary sensory and autonomic neuropathy
type III) is a rare autosomal recessive disease characterized by impaired development
of primary sensory and autonomic neurons resulting in a severe neurological phenotype,
which includes arterial baroreflex and chemoreflex failure with high frequency of
sleep-disordered breathing and sudden death during sleep. Although a rare disease,
familial dysautonomia represents a unique template to study the interactions between
sleep-disordered breathing and abnormal chemo- and baroreflex function. In patients
with familial dysautonomia, ventilatory responses to hypercapnia are reduced, and
to hypoxia are almost absent. In response to hypoxia, these patients develop paradoxical
hypoventilation, hypotension, bradycardia, and potentially, death. Impaired ventilatory
control due to chemoreflex failure acquires special relevance during sleep when conscious
control of respiration withdraws. Overall, almost all adult (85%) and pediatric (95%)
patients have some degree of sleep-disordered breathing. Obstructive apnea events
are more frequent in adults, whereas central apnea events are more severe and frequent
in children. The annual incidence rate of sudden death during sleep in patients with
familial dysautonomia is 3.4 per 1000 person-year, compared to 0.5–1 per 1000 person-year
of sudden unexpected death in epilepsy. This review summarizes recent developments
in the understanding of sleep-disordered breathing in patients with familial dysautonomia,
the risk factors for sudden death during sleep, and the specific interventions that
could prevent it.
Keywords
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Article info
Publication history
Published online: February 14, 2019
Accepted:
February 11,
2019
Received:
January 8,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
