Congenital central hypoventilation syndrome (CCHS) is a rare condition that usually presents soon after birth and is potentially life-shortening if not treated. The defining abnormality is a persistent hypoventilation, most pronounced during sleep, with relative insensitivity to hypercarbia and a lesser insensitivity to hypoxia, beginning in the neonatal period and requiring life-long ventilatory assistance. Changes in the integration of afferent inputs from central and peripheral chemoreceptors in the brainstem are the most likely disease mechanisms.
The association of congenital failure of autonomic control with congenital central hypoventilation syndrome was first reported in 1978. This syndrome is rare; only about 50 cases have been reported worldwide. Congenital failure of autonomic control is a condition caused by congenital absence of ganglion cells from the enteric nervous system, resulting in bowel obstruction ranging in severity from chronic severe constipation to complete obstruction and early neonatal death. It is thought to originate in a failure of migration of neural crest derived precursor cells, although this is controversial and a hostile gut microenvironment may also contribute.
Congenital failure of autonomic control can be caused by mutation in the paired-liked homeobox 2B (PHOX2B) gene as well as in several other genes, including RET, GDNF, EDN3, and BDNF. PHOX2B is the major disease-causing gene, mutated in half to two thirds of patients with congenital failure of autonomic control.