Abstract □ 10

In 1970, Mellins and Colleagues provided the first report on CCHS and eight years later, the association between CCHS and Hirschsprung's disease (HSCR) was made. One hundred and sixty seven cases of CCHS have been reported since 1970. The majority of cases are sporadic. However, few familial cases have been reported. The respiratory phenotype of CCHS is characterized by hypoventilation during sleep especially during non-rapid-eye-movement sleep. In the most severe cases, hypoventilation occurs during wakefulness and patients require ventilation support both awake and asleep. The pathophysiological mechanisms underlying CCHS remain elusive, but altered integration of afferent imputs from chemoreceptors at the brainstem level has been advanced as the most likely mechanism. In addition to dysfunction in the control of breathing, CCHS patients may exhibit abnormal control of heart rate. Furthermore, swallowing difficulty and ocular abnormalities have been reported. CCHS is associated with HSCR in 27 % of the reported cases. The phenotype of HSCR associated with CCHS is different from that of ordinary HSCH, i.e. long or total aganglionic segment in 76 % of the cases and sex ratio equal to 1. CCHS has recently become a target for genetic analysis. Mutations of genes involved in the development of neural crest cells, including ret, glial-derived-neurotrophic-factor, and endothelin-3, have been reported in four children with CCHS. The involvement of at least three genes belonging to distinct signaling pathways suggest that an interactive polygenic inherance may be involved in CCHS.