Hypoventilation Syndromes of Infancy, Childhood, and Adulthood Congenital Central Hypoventilation Syndrome (CCHS), Later-Onset CCHS, and Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Rehan Saiyed, BS a , Casey M. Rand, BS a , Michael S. Carroll, PhD a,b , Debra E. Weese-Mayer, MD a,b, * a Center for Autonomic Medicine in Pediatrics (CAMP), Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Chicago, IL 60611, USA; b Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA * Corresponding author. Center for Autonomic Medicine in Pediatrics (CAMP), Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Box 165, Chicago, IL 60611. E-mail address: D-Weese-Mayer@Northwestern.edu KEYWORDS  Autonomic dysregulation  Hypothalamic dysregulation  Hypoventilation  PHOX2B KEY POINTS  Congenital central hypoventilation syndrome (CCHS) (including later-onset CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare neurocristopathies with shared features including alveolar hypoventilation, disordered res- piratory control, variable autonomic nervous system dysregulation (ANSD), tumors of neural crest origin, and risk of sudden death.  Mutations in the PHOX2B gene are causative in all known cases of CCHS. The PHOX2B genotype is predictive of many features of the CCHS phenotype, including severity of hypoventilation, risk of cardiac sinus pauses, Hirschsprung disease, neural crest tumors, and symptoms of ANSD.  For ROHHAD, research is under way to determine the etiology of the disease.  Early consideration of CCHS and stepwise PHOX2B testing in cases with unexplained alveolar hy- poventilation or delayed recovery of spontaneous breathing after sedation, anesthesia, or a severe respiratory infection will enhance diagnosis of milder CCHS cases and LO-CCHS, decreasing morbidity and mortality in these instances.  Heightened clinical suspicion in cases of rapid-onset obesity with hypoventilation, especially in the event of a tumor of neural crest origin, will allow for early identification of ROHHAD patients. Coupled with conservative management, this strategy will optimize the long-term outcome and neurocognitive development for children with ROHHAD.  For CCHS, LO-CCHS, and ROHHAD, targets for treatment and drug intervention are being evalu- ated as progress is made in understanding the underlying mechanisms and phenotypic manifesta- tions of these disorders. Sleep Med Clin 9 (2014) 425–439 http://dx.doi.org/10.1016/j.jsmc.2014.06.001 1556-407X/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved. sleep.theclinics.com