Novel insights into congenital hypoventilation syndrome.
Congenital central hypoventilation syndrome (CCHS) is a rare and unique condition that may prompt unparalleled approaches to the discovery of genes involved in development of cardiorespiratory control and gas exchange homeostasis. Its higher risk of recurrence in families and its association with Hirschsprung's disease suggest that an underlying genetic mechanism is involved. However, screening for mutations of the receptor tyrosine kinase RET and endothelin 3 has revealed only occasional patients affected by these mutations, therefore suggesting that CCHS may result from disruption of more than a single gene. In recent years, three principal issues have become apparent: 1) the autonomic nervous system is involved universally in CCHS cases, albeit to a varying extent; 2) the use of novel functional imaging approaches incorporating refined stimulus paradigms may provide essential research and clinical insights into localization and assessment of neural sites underlying the phenotypic expression of this syndrome; and 3) efforts to transition patients' nocturnal respiratory support to a noninvasive ventilatory modality should be critically evaluated and pursued, when appropriate, to improve the quality of life for patients and families.
Gozal
D
D
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. dgozal@tmcpop.tmc.tulane.edu
Harper
R M
RM
D001341:Autonomic Nervous System / Q000503:physiopathology; D029721:Drosophila Proteins; D019334:Endothelin-3 / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D011659:Pulmonary Gas Exchange / Q000235:genetics; D011788:Quality of Life; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012119:Respiration / Q000235:genetics; D012138:Respiratory Therapy; D020182:Sleep Apnea, Central / Q000151:congenital* / Q000235:genetics; D013577:Syndrome
D029721:Drosophila Proteins; D019334:Endothelin-3; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila