Congenital central hypoventilation syndrome: diagnosis, management, and long-term outcome in thirty-two children

Disease characteristics. Classic congenital central hypoventilation syndrome (CCHS) is characterized by adequate ventilation while the affected individual is awake and by hypoventilation with normal respiratory rates and shallow breathing during sleep; more severely affected individuals hypoventilate when both awake and asleep. Both phenotypes present in the newborn period. Children with CCHS often have physiologic and anatomic manifestations of a generalized autonomic nervous system dysfunction/dysregulation (ANSD); a subset have altered development of neural crest-derived structures (i.e., Hirschsprung disease) and tumors of neural crest origin including neuroblastoma, ganglioneuroma, and ganglioneuroblastoma. Recently, it has been recognized that some individuals with nocturnal alveolar hypoventilation, features of ANSD, and a polyalanine expansion mutation in PHOX2B characteristic of CCHS do not present until childhood or adulthood. Many individuals with CCHS who have been successfully ventilated are now in their 20s, suggesting the potential for a normal life span. Diagnosis/testing. Diagnosis of CCHS is established by clinical findings and confirmatory molecular genetic testing. All individuals with the comprehensive CCHS phenotype ar