Peripheral chemoreceptors in congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome is a rare disorder caused by a mutation in the PHOX2B gene resulting in hypoventilation that is worse during sleep. Human physiologic studies show that patients with CCHS have absent or decreased rebreathing ventilatory responses to hypercapnia and hypoxemia during sleep as well as during wakefulness. Some ventilatory responses to hypoxia and hyperoxia can be demonstrated using a step change in inspired oxygen. However, these suggest that both central and peripheral chemoreceptor functions are generally defective in all states in children with CCHS. The defect in CCHS may lie in central nervous system pathways regulating ventilation, whose development and function are controlled by PHOX2B. Moreover, the retrotrapezoid nucleus (RTN) may be the major defect in CCHS, where central and peripheral inputs converge. Human physiological studies predicted that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals. New evidence suggests the RTN may be the respiratory controller where chemoreceptor inputs are integrated. In this review we present the clinical presentation of CCHS, revisit results of human physiologic studies, and discuss the findings in light of new knowledge about the role of PHOX2B and RTN in CCHS.