Congenital central hypoventilation syndrome and the PHOX2B gene mutation

Congenital central hypoventilation syndrome (CCHS) is a rare syndrome of dysfunction of the autonomic nervous system characterized by a decreased response to hypercarbia. It is a disorder in which affected individuals fail to breathe during sleep despite progressive hypercapnia and hypoxia. Infants simply fall asleep and quit breathing. They are found by their parents or caregivers blue and lifeless. CCHS is an autosomal dominant disease. It has been linked with tumors of neural crest origin, segmental aganglionosis of the colon, and diffuse autonomic dysregulation but can occur alone. Discovery of the genetic link between the paired-like homeobox 2B (PHOX2B) genetic mutations and CCHS represents a breakthrough in the diagnosis of CCHS, association of mutated alleles with disease severity, and clues to the pathophysiology responsible for the disorder. Early genetic screening and intervention can provide the families of these infants with hope for achieving a normal life.