Comprehensive Physiology Wiley Online Library

Genetic Diseases: Congenital Central Hypoventilation, Rett, and Prader‐Willi Syndromes

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The present review summarizes current knowledge on three rare genetic disorders of respiratory control, congenital central hypoventilation syndrome (CCHS), Rett syndrome (RTT), and Prader‐Willi syndrome (PWS). CCHS is characterized by lack of ventilatory chemosensitivity caused by PHOX2B gene abnormalities consisting mainly of alanine expansions. RTT is associated with episodes of tachypneic and irregular breathing intermixed with breathholds and apneas and is caused by mutations in the X‐linked MECP2 gene encoding methyl‐CpG‐binding protein. PWS manifests as sleep‐disordered breathing with apneas and episodes of hypoventilation and is caused by the loss of a group of paternally inherited genes on chromosome 15. CCHS is the most specific disorder of respiratory control, whereas the breathing disorders in RTT and PWS are components of a more general developmental disorder. The main clinical features of these three disorders are reviewed with special emphasis on the associated brain abnormalities. In all three syndromes, disease‐causing genetic defects have been identified, allowing the development of genetically engineered mouse models. New directions for future therapies based on these models or, in some cases, on clinical experience are delineated. Studies of CCHS, RTT, and PWS extend our knowledge of the molecular and cellular aspects of respiratory rhythm generation and suggest possible pharmacological approaches to respiratory control disorders. This knowledge is relevant for the clinical management of many respiratory disorders that are far more prevalent than the rare diseases discussed here. © 2012 American Physiological Society. Compr Physiol 2:2255‐2279, 2012.

 1. Abdala AP, Dutschmann M, Bissonnette JM, Paton JF. Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 107: 18208‐18213, 2010.
 2. Aizenfisz S, Dauger S, Durand E, Vardon G, Levacher B, Simonneau M, Pachnis V, Gaultier C, Gallego J. Ventilatory responses to hypercapnia and hypoxia in heterozygous c‐ret newborn mice. Respir Physiolo Neurobiol 131: 213‐222, 2002.
 3. Akefeldt A, Ekman R, Gillberg C, Mansson JE. Cerebrospinal fluid monoamines in Prader‐Willi syndrome. Biol Psychiatry 44: 1321‐1328, 1998.
 4. Al Dabal L, Bahammam AS. Obesity hypoventilation syndrome. Ann Thorac Med 4: 41‐49, 2009.
 5. Amiel J, Dubreuil V, Ramanantsoa N, Fortin G, Gallego J, Brunet JF, Goridis C. PHOX2B in respiratory control: Lessons from congenital central hypoventilation syndrome and its mouse models. Respir Physiol Neurobiol 168: 125‐132, 2009.
 6. Amiel J, Laudier B, Attie‐Bitach T, Trang H, de Pontual L, Gener B, Trochet D, Etchevers H, Ray P, Simonneau M, Vekemans M, Munnich A, Gaultier C, Lyonnet S. Polyalanine expansion and frameshift mutations of the paired‐like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33: 459‐461, 2003.
 7. Amiel J, Sproat‐Emison E, Garcia‐Barcelo M, Lantieri F, Burzynski G, Borrego S, Pelet A, Arnold S, Miao X, Griseri P, Brooks AS, Antinolo G, de Pontual L, Clement‐Ziza M, Munnich A, Kashuk C, West K, Wong KK, Lyonnet S, Chakravarti A, Tam PK, Ceccherini I, Hofstra RM, Fernandez R. Hirschsprung disease, associated syndromes and genetics: A review. J Med Genet 45: 1‐14, 2008.
 8. Amir R, Dahle EJ, Toriolo D, Zoghbi HY. Candidate gene analysis in Rett syndrome and the identification of 21 SNPs in Xq. Am J Med Genet 90: 69‐71, 2000.
 9. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X‐linked MECP2, encoding methyl‐CpG‐binding protein 2. Nat Genet 23: 185‐188, 1999.
 10. Andaku DK, Mercadante MT, Schwartzman JS. Buspirone in Rett syndrome respiratory dysfunction. Brain Dev 27: 437‐438, 2005.
 11. Andrieu D, Watrin F, Niinobe M, Yoshikawa K, Muscatelli F, Fernandez PA. Expression of the Prader‐Willi gene Necdin during mouse nervous system development correlates with neuronal differentiation and p75NTR expression. Gene Expr Patterns 3: 761‐765, 2003.
 12. Antic NA, Malow BA, Lange N, McEvoy RD, Olson AL, Turkington P, Windisch W, Samuels M, Stevens CA, Berry‐Kravis EM, Weese‐Mayer DE. PHOX2B mutation‐confirmed congenital central hypoventilation syndrome: Presentation in adulthood. Am J Respir Crit Care Med 174: 923‐927, 2006.
 13. Archer HL, Evans JC, Millar DS, Thompson PW, Kerr AM, Leonard H, Christodoulou J, Ravine D, Lazarou L, Grove L, Verity C, Whatley SD, Pilz DT, Sampson JR, Clarke AJ. NTNG1 mutations are a rare cause of Rett syndrome. Am J Med Genet A 140: 691‐694, 2006.
 14. Archer HL, Whatley SD, Evans JC, Ravine D, Huppke P, Kerr A, Bunyan D, Kerr B, Sweeney E, Davies SJ, Reardon W, Horn J, MacDermot KD, Smith RA, Magee A, Donaldson A, Crow Y, Hermon G, Miedzybrodzka Z, Cooper DN, Lazarou L, Butler R, Sampson J, Pilz DT, Laccone F, Clarke AJ. Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients. J Med Genet 43: 451‐456, 2006.
 15. Arens R, Gozal D, Burrell BC, Bailey SL, Bautista DB, Keens TG, Ward SL. Arousal and cardiorespiratory responses to hypoxia in Prader‐Willi syndrome. Am J Respir Crit Care Med 153: 283‐287, 1996.
 16. Armstrong D, Dunn JK, Antalffy B, Trivedi R. Selective dendritic alterations in the cortex of Rett syndrome. J Neuropathol Exp Neurol 54: 195‐201, 1995.
 17. Bachetti T, Bocca P, Borghini S, Matera I, Prigione I, Ravazzolo R, Ceccherini I. Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions. Int J Biochem Cell Biol 39: 327‐339, 2007.
 18. Bachetti T, Ceccherini I. In vitro studies of PHOX2B gene mutations in congenital central hypoventilation syndrome. In: Gaultier C, editor. PHOX2B Polyalanine Expansions and Frameshift Mutations. New York: Springer, 2008, pp. 71‐83.
 19. Bachetti T, Matera I, Borghini S, Di Duca M, Ravazzolo R, Ceccherini I. Distinct pathogenetic mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in congenital central hypoventilation syndrome. Hum Mol Genet 14: 1815‐1824, 2005.
 20. Bachetti T, Parodi S, Di Duca M, Santamaria G, Ravazzolo R, Ceccherini I. Low amounts of PHOX2B expanded alleles in asymptomatic parents suggest unsuspected recurrence risk in congenital central hypoventilation syndrome. J Mol Med 89: 505‐513, 2011.
 21. Balkowiec A, Katz DM. Brain‐derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. J Physiol 510(Pt 2): 527‐533, 1998.
 22. Balkowiec A, Kunze DL, Katz DM. Brain‐derived neurotrophic factor acutely inhibits AMPA‐mediated currents in developing sensory relay neurons. J Neurosci 20: 1904‐1911, 2000.
 23. Barratt S, Kendrick AH, Buchanan F, Whittle AT. Central hypoventilation with PHOX2B expansion mutation presenting in adulthood. Thorax 62: 919‐920, 2007.
 24. Bayliss DA, Millhorn DE. Central neural mechanisms of progesterone action: Application to the respiratory system. J Appl Physiol 73: 393‐404, 1992.
 25. Bayliss DA, Millhorn DE, Gallman EA, Cidlowski JA. Progesterone stimulates respiration through a central nervous system steroid receptor‐mediated mechanism in cat. Proc Natl Acad Sci U S A 84: 7788‐7792, 1987.
 26. Bebbington A, Anderson A, Ravine D, Fyfe S, Pineda M, de Klerk N, Ben‐Zeev B, Yatawara N, Percy A, Kaufmann WE, Leonard H. Investigating genotype‐phenotype relationships in Rett syndrome using an international data set. Neurology 70: 868‐875, 2008.
 27. Ben‐Mabrouk F, Tryba AK. Substance P modulation of TRPC3/7 channels improves respiratory rhythm regularity and ICAN‐dependent pacemaker activity. Eur J Neurosci 31: 1219‐1232, 2010.
 28. Berry‐Kravis EM, Zhou L, Rand CM, Weese‐Mayer DE. Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit Care Med 174: 1139‐1144, 2006.
 29. Bienvenu T and Chelly J. Molecular genetics of Rett syndrome: When DNA methylation goes unrecognized. Nat Rev Genet 7: 415‐426, 2006.
 30. Bischof JM, Stewart CL, Wevrick R. Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader‐Willi syndrome. Hum Mol Genet 16: 2713‐2719, 2007.
 31. Bissonnette J, Hilaire G. Possible role of bioaminergic systems in the respiratory disorders of Rett syndrome. In: Gaultier C, editor. Genetic Basis of Respiratory Control Disorder. New York: Springer, 2008, pp. 271‐290.
 32. Bissonnette JM, Knopp SJ. Effect of inspired oxygen on periodic breathing in methy‐CpG‐binding protein 2 (Mecp2) deficient mice. J Appl Physiol 104: 198‐204, 2008.
 33. Bissonnette JM, Knopp SJ. Separate respiratory phenotypes in methyl‐CpG‐binding protein 2 (Mecp2) deficient mice. Pediatr Res 59: 513‐518, 2006.
 34. Blum AS. Respiratory physiology of seizures. J Clin Neurophysiol 26: 309‐315, 2009.
 35. Bolk S, Angrist M, Xie J, Yanagisawa M, Silvestri JM, Weese‐Mayer DE, Chakravarti A. Endothelin‐3 frameshift mutation in congenital central hypoventilation syndrome. Nat Genet 13: 395‐396, 1996.
 36. Bouslama M, Chauviere L, Fontaine RH, Matrot B, Gressens P, Gallego J. Treatment‐induced prevention of learning deficits in newborn mice with brain lesions. Neuroscience 141: 795‐801, 2006.
 37. Bouslama M, Durand E, Van den Bergh O, Gallego J. Olfactory classical conditioning in newborn mice. Behav Brain Res 161: 102‐106, 2005.
 38. Bouslama M, Renaud J, Olivier P, Fontaine RH, Matrot B, Gressens P, Gallego J. Melatonin prevents learning disorders in brain‐lesioned newborn mice. Neuroscience 150: 712‐719, 2007.
 39. Bouvier J, Autran S, Fortin G, Champagnat J, Thoby‐Brisson M. Acute role of the brain‐derived neurotrophic factor (BDNF) on the respiratory neural network activity in mice in vitro. J Physiol Paris 100: 290‐296, 2006.
 40. Boyle J, Hawkins M, Barton DE, Meaney K, Guitart M, O'Grady A, Tobi S, Ramsden SC, Elles R, Gray E, Metcalfe P, Hawkins JR. Establishment of the first WHO international genetic reference panel for Prader Willi and Angelman syndromes. Eur J Hum Genet 19: 857‐864, 2011.
 41. Brown LY and Brown SA. Alanine tracts: The expanding story of human illness and trinucleotide repeats. Trends Genet 20: 51‐58, 2004.
 42. Brunet JF, Goridis C. Phox2b and the homeostatic brain. In: Gaultier C, editor. Genetic Basis for Respiratory Control Disorders. New york: Springer, 2008, pp. 25‐38.
 43. Brunet JF, Pattyn A. Phox2 genes ‐ from patterning to connectivity. Curr Opin Genet Dev 12: 435‐440, 2002.
 44. Burton MD, Kawashima A, Brayer JA, Kazemi H, Shannon DC, Schuchardt A, Costantini F, Pachnis V, Kinane TB. RET proto‐oncogene is important for the development of respiratory CO2 sensitivity. J Auton Nerv Syst 63: 137‐143, 1997.
 45. Calfa G, Percy AK, Pozzo‐Miller L. Experimental models of Rett syndrome based on Mecp2 dysfunction. Exp Biol Med (Maywood) 236: 3‐19, 2011.
 46. Carroll MS, Patwari PP, Weese‐Mayer DE. Carbon dioxide chemoreception and hypoventilation syndromes with autonomic dysregulation. J Appl Physiol 108: 979‐988, 2010.
 47. Cassidy SB, Driscoll DJ. Prader‐Willi syndrome. Eur J Hum Genet 17: 3‐13, 2009.
 48. Chadwick LH, Wade PA. MeCP2 in Rett syndrome: Transcriptional repressor or chromatin architectural protein? Curr Opin Genet Dev 17: 121‐125, 2007.
 49. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320: 1224‐1229, 2008.
 50. Chahrour M and Zoghbi HY. The story of Rett syndrome: From clinic to neurobiology. Neuron 56: 422‐437, 2007.
 51. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49: 341‐348, 2006.
 52. Chen RZ, Akbarian S, Tudor M, Jaenisch R. Deficiency of methyl‐CpG binding protein‐2 in CNS neurons results in a Rett‐like phenotype in mice. Nat Genet 27: 327‐331, 2001.
 53. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, Jaenisch R, Greenberg ME. Derepression of BDNF transcription involves calcium‐dependent phosphorylation of MeCP2. Science 302: 885‐889, 2003.
 54. Clouthier DE, Hosoda K, Richardson JA, Williams SC, Yanagisawa H, Kuwaki T, Kumada M, Hammer RE, Yanagisawa M. Cranial and cardiac neural crest defects in endothelin‐a receptor‐deficient mice. Development 125: 813‐824, 1998.
 55. Cobb S, Guy J, Bird A. Reversibility of functional deficits in experimental models of Rett syndrome. Biochem Soc Trans 38: 498‐506, 2010.
 56. Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, David Sweatt J, Zoghbi HY. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13: 2679‐2689, 2004.
 57. Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P, et al. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375: 235‐238, 1995.
 58. Cross SH, Morgan JE, Pattyn A, West K, McKie L, Hart A, Thaung C, Brunet JF, Jackson IJ. Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: Mechanistic insights into human congenital central hypoventilation syndrome. Hum Mol Genet 13: 1433‐1439, 2004.
 59. Dauger S, Guimiot F, Renolleau S, Levacher B, Boda B, Mas C, Nepote V, Simonneau M, Gaultier C, Gallego J. MASH‐1/RET pathway involvement in development of brain stem control of respiratory frequency in newborn mice. Physiol Genomics 7: 149‐157, 2001.
 60. Dauger S, Pattyn A, Lofaso F, Gaultier C, Goridis C, Gallego J, Brunet JF. Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways. Development 130: 6635‐6642, 2003.
 61. Dauger S, Renolleau S, Vardon G, Nepote V, Mas C, Simonneau M, Gaultier C, Gallego J. Ventilatory responses to hypercapnia and hypoxia in Mash‐1 heterozygous newborn and adult mice. Pediatr Res 46: 535‐542, 1999.
 62. Dauvilliers Y, Stal V, Abril B, Coubes P, Bobin S, Touchon J, Escourrou P, Parker F, Bourgin P. Chiari malformation and sleep related breathing disorders. J Neurol Neurosurg Psychiatry 78: 1344‐1348, 2007.
 63. De Filippis B, Ricceri L, Laviola G. Investigating Rett syndrome through genetic mouse models: Presymptomatic, clearly symptomatic phases, and innovative therapeutic approaches. In: Transgenic and Mutant Tools to Model Brain Disorders. New York: Humana Press 44(2): 151‐178, 2010.
 64. de Lind van Wijngaarden RF, Joosten KF, van den Berg S, Otten BJ, de Jong FH, Sweep CG, de Weerd AW, Hokken‐Koelega AC. The relationship between central adrenal insufficiency and sleep‐related breathing disorders in children with Prader‐Willi syndrome. J Clin Endocrinol Metab 94: 2387‐2393, 2009.
 65. Deguchi K, Antalffy BA, Twohill LJ, Chakraborty S, Glaze DG, Armstrong DD. Substance P immunoreactivity in Rett syndrome. Pediatr Neurol 22: 259‐266, 2000.
 66. Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U. SnoRNA Snord116 (Pwcr1/MBII‐85) deletion causes growth deficiency and hyperphagia in mice. PLoS One 3: e1709, 2008.
 67. Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho‐Montero C, Nicholls RD, Francke U. Lack of Pwcr1/MBII‐85 snoRNA is critical for neonatal lethality in Prader‐Willi syndrome mouse models. Mamm Genome 16: 424‐431, 2005.
 68. Dubreuil V, Barhanin J, Goridis C, Brunet JF. Breathing with phox2b. Philos Trans R Soc Lond B Biol Sci 364: 2477‐2483, 2009.
 69. Dubreuil V, Ramanantsoa N, Trochet D, Vaubourg V, Amiel J, Gallego J, Brunet JF, Goridis C. A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons. Proc Natl Acad Sci U S A 105: 1067‐1072, 2008.
 70. Dubreuil V, Thoby‐Brisson M, Rallu M, Persson K, Pattyn A, Birchmeier C, Brunet JF, Fortin G, Goridis C. Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons. J Neurosci 29: 14836‐14846, 2009.
 71. Dudley O and Muscatelli F. Prader‐Willi syndrome. In: Clément K, Sorensen TIA, editors. Obesity: Genomics and Postgenomics. New York: Informa Healthcare, 2008, pp. 179‐194.
 72. Dura E, Villard L, Roux JC. Expression of methyl CpG binding protein 2 (Mecp2) during the postnatal development of the mouse brainstem. Brain Res 1236: 176‐184, 2008.
 73. Durand E, Dauger S, Pattyn A, Gaultier C, Goridis C, Gallego J. Sleep‐disordered breathing in newborn mice heterozygous for the transcription factor Phox2b. Am J Respir Crit Care Med 172: 238‐243, 2005.
 74. Eiholzer U. Deaths in children with Prader‐Willi syndrome. A contribution to the debate about the safety of growth hormone treatment in children with PWS. Horm Res 63: 33‐39, 2005.
 75. Einspieler C, Kerr AM, Prechtl HF. Abnormal general movements in girls with Rett disorder: The first four months of life. Brain Dev 27(Suppl 1): S8‐S13, 2005.
 76. Einspieler C, Kerr AM, Prechtl HF. Is the early development of girls with Rett disorder really normal? Pediatr Res 57: 696‐700, 2005.
 77. Erickson JT, Brosenitsch TA, Katz DM. Brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. J Neurosci 21: 581‐589, 2001.
 78. Erickson JT, Conover JC, Borday V, Champagnat J, Barbacid M, Yancopoulos G, Katz DM. Mice lacking brain‐derived neurotrophic factor exhibit visceral sensory neuron losses distinct from mice lacking NT4 and display a severe developmental deficit in control of breathing. J Neurosci 16: 5361‐5371, 1996.
 79. Erlandson A, Hagberg B. MECP2 abnormality phenotypes: Clinicopathologic area with broad variability. J Child Neurol 20: 727‐732, 2005.
 80. Feldman JL, Del Negro CA. Looking for inspiration: New perspectives on respiratory rhythm. Nat Rev Neurosci 7: 232‐242, 2006.
 81. Feldman JL, Janczewski WA. The Last Word: Point:Counterpoint authors respond to commentaries on “the parafacial respiratory group (pFRG)/pre‐Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal”. J Appl Physiol 101: 689, 2006.
 82. Ferri R, Curzi‐Dascalova L, Del Gracco S, Elia M, Musumeci SA, Stefanini MC. Respiratory patterns during sleep in Down's syndrome:importance of central apnoeas. J Sleep Res 6: 134‐141, 1997.
 83. Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken‐Koelega AC. Sleep‐related breathing disorders in prepubertal children with Prader‐Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab 91: 4911‐4915, 2006.
 84. Gallego J, Dauger S. PHOX2B mutations and ventilatory control. Respir Physiol Neurobiol 164: 49‐54, 2008.
 85. Gallego J, Ramanantsoa N, Vaubourg V. Tentative mouse model for the congenital central hypoventilation syndrome: Heterozygous phox2b mutant newborn mice. In: Gaultier C, editor. Genetic Basis for Respiratory Control Disorders, New York: Springer, 2008, pp. 243‐254.
 86. Gerard M, Hernandez L, Wevrick R, Stewart CL. Disruption of the mouse necdin gene results in early post‐natal lethality. Nat Genet 23: 199‐202, 1999.
 87. Giacometti E, Luikenhuis S, Beard C, Jaenisch R. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A 104: 1931‐1936, 2007.
 88. Glaze DG, Frost JD, Jr., Zoghbi HY, Percy AK. Rett's syndrome: Characterization of respiratory patterns and sleep. Ann Neurol 21: 377‐382, 1987.
 89. Glaze DG, Percy AK, Skinner S, Motil KJ, Neul JL, Barrish JO, Lane JB, Geerts SP, Annese F, Graham J, McNair L, Lee HS. Epilepsy and the natural history of Rett syndrome. Neurology 74: 909‐912, 2010.
 90. Goldstone AP. Prader‐Willi syndrome: Advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 15: 12‐20, 2004.
 91. Goldstone AP, Holland AJ, Hauffa BP, Hokken‐Koelega AC, Tauber M. Recommendations for the diagnosis and management of Prader‐Willi syndrome. J Clin Endocrinol Metab 93: 4183‐4197, 2008.
 92. Gonzalez C, Almaraz L, Obeso A, Rigual R. Carotid body chemoreceptors: From natural stimuli to sensory discharges. Physiol Rev 74: 829‐898, 1994.
 93. Goridis C, Brunet JF. Transcriptional control of neurotransmitter phenotype. Curr Opin Neurobiol 9: 47‐53, 1999.
 94. Goridis C, Brunet JF. Central chemoreception: Lessons from mouse and human genetics. Respir Physiol Neurobiol 173: 312‐321, 2010.
 95. Goridis C, Rohrer H. Specification of catecholaminergic and serotonergic neurons. Nat Rev Neurosci 3: 531‐541, 2002.
 96. Gosalakkal JA. Sleep‐disordered breathing in Chiari malformation type 1. Pediatr Neurol 39: 207‐208, 2008.
 97. Goyal M, O'Riordan MA, Wiznitzer M. Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome. J Child Neurol 19: 588‐591, 2004.
 98. Gozal D. Congenital central hypoventilation syndrome: An update. Pediatr Pulmonol 26: 273‐282, 1998.
 99. Gozal D, Arens R, Omlin KJ, Ward SL, Keens TG. Absent peripheral chemosensitivity in Prader‐Willi syndrome. J Appl Physiol 77: 2231‐2236, 1994.
 100. Gronli JO, Santucci BA, Leurgans SE, Berry‐Kravis EM, Weese‐Mayer DE. Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatr Pulmonol 43: 77‐86, 2008.
 101. Guillemot F, Joyner AL. Dynamic expression of the murine achaete‐scute homologue Mash‐1 in the developing nervous system. Mech Dev 42: 171‐185, 1993.
 102. Gunay‐Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB. The changing purpose of Prader‐Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 108: E92, 2001.
 103. Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science 315: 1143‐1147, 2007.
 104. Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2‐null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27: 322‐326, 2001.
 105. Guyenet PG, Mulkey DK. Retrotrapezoid nucleus and parafacial respiratory group. Respir Physiol Neurobiol 173: 244‐255, 2010.
 106. Guyenet PG, Stornetta RL, Abbott SB, Depuy SD, Fortuna MG, Kanbar R. Central CO2‐chemoreception and integrated neural mechanisms of cardiovascular and respiratory control. J Appl Physiol, 108: 995‐1002, 2010.
 107. Hagberg H, Peebles D, Mallard C. Models of white matter injury: Comparison of infectious, hypoxic‐ischemic, and excitotoxic insults. Ment Retard Dev Disabil Res Rev 8: 30‐38, 2002.
 108. Hager A, Koch W, Stenzel H, Hess J, Schober J. Effects of movement and work load in patients with congenital central hypoventilation syndrome. Eur J Cardiovasc Prev Rehabil 14: 294‐298, 2007.
 109. Hamilton J, Bodurtha JN. Congenital central hypoventilation syndrome and Hirschsprung's disease in half sibs. J Med Genet 26: 272‐274, 1989.
 110. Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, LaFranchi SH. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader‐Willi syndrome. J Clin Endocrinol Metab 88: 2206‐2212, 2003.
 111. Harper R, Woo M, Macey P, Kumar R. Structural and functional brain abnormalities in congenital central hypoventilation syndrome. In: Gaultier C, editor. Genetic Basis for Respiratory Control Disorders. New York: Springer, 2008, pp. 57‐70.
 112. Harper RM, Macey PM, Woo MA, Macey KE, Keens TG, Gozal D, Alger JR. Hypercapnic exposure in congenital central hypoventilation syndrome reveals CNS respiratory control mechanisms. J Neurophysiol 93: 1647‐1658, 2005.
 113. Healy F, Marcus C. Congenital central hypoventilation syndrome. Paediat Respir Rev 12: 253‐263, 2011.
 114. Hilaire G, Duron B. Maturation of the mammalian respiratory system. Physiol Rev 79: 325‐360, 1999.
 115. Hilaire G, Voituron N, Menuet C, Ichiyama RM, Subramanian HH, Dutschmann M. The role of serotonin in respiratory function and dysfunction. Respir Physiol Neurobiol 174: 76‐88, 2010.
 116. Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochem Cell Biol 87: 219‐227, 2009.
 117. Hodges MR, Richerson GB. Medullary serotonin neurons and their roles in central respiratory chemoreception. Respir Physiol Neurobiol 173: 256‐263, 2010.
 118. Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F. Prader‐Willi syndrome: Consensus diagnostic criteria. Pediatrics 91: 398‐402, 1993.
 119. Huang L, Guo H, Hellard DT, Katz DM. Glial cell line‐derived neurotrophic factor (GDNF) is required for differentiation of pontine noradrenergic neurons and patterning of central respiratory output. Neuroscience 130: 95‐105, 2005.
 120. Ide S, Itoh M, Goto Y. Defect in normal developmental increase of the brain biogenic amine concentrations in the mecp2‐null mouse. Neurosci Lett 386: 14‐17, 2005.
 121. Ishigaki K, Ito Y, Sawaishi Y, Kodaira K, Funatsuka M, Hattori N, Nakano K, Saito K, Osawa M. TRH therapy in a patient with juvenile Alexander disease. Brain Dev 28: 663‐667, 2006.
 122. Isoda K, Morimoto M, Matsui F, Hasegawa T, Tozawa T, Morioka S, Chiyonobu T, Nishimura A, Yoshimoto K, Hosoi H. Postnatal changes in serotonergic innervation to the hippocampus of methyl‐CpG‐binding protein 2‐null mice. Neuroscience 165: 1254‐1260, 2010.
 123. Iughetti L, Bosio L, Corrias A, Gargantini L, Ragusa L, Livieri C, Predieri B, Bruzzi P, Caselli G, Grugni G. Pituitary height and neuroradiological alterations in patients with Prader‐Labhart‐Willi syndrome. Eur J Pediatr 167: 701‐702, 2008.
 124. Janczewski WA, Feldman JL. Novel data supporting the two respiratory rhythm oscillator hypothesis. Focus on “respiration‐related rhythmic activity in the rostral medulla of newborn rats”. J Neurophysiol 96: 1‐2, 2006.
 125. Jay P, Rougeulle C, Massacrier A, Moncla A, Mattei MG, Malzac P, Roeckel N, Taviaux S, Lefranc JL, Cau P, Berta P, Lalande M, Muscatelli F. The human necdin gene, NDN, is maternally imprinted and located in the Prader‐Willi syndrome chromosomal region. Nat Genet 17: 357‐361, 1997.
 126. Jentarra GM, Olfers SL, Rice SG, Srivastava N, Homanics GE, Blue M, Naidu S, Narayanan V. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X‐linked mental retardation. BMC Neurosci 11: 19, 2010.
 127. Julu PO, Kerr AM, Apartopoulos F, Al‐Rawas S, Engerstrom IW, Engerstrom L, Jamal GA, Hansen S. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child 85: 29‐37, 2001.
 128. Kang BJ, Chang DA, Mackay DD, West GH, Moreira TS, Takakura AC, Gwilt JM, Guyenet PG, Stornetta RL. Central nervous system distribution of the transcription factor Phox2b in the adult rat. J Comp Neurol 503: 627‐641, 2007.
 129. Katz DM. Neuronal growth factors and development of respiratory control. Respir Physiol Neurobiol 135: 155‐165, 2003.
 130. Katz DM, Dutschmann M, Ramirez JM, Hilaire G. Breathing disorders in Rett syndrome: Progressive neurochemical dysfunction in the respiratory network after birth. Respir Physiol Neurobiol 168: 101‐108, 2009.
 131. Kerr AM. A review of the respiratory disorder in the Rett syndrome. Brain Dev 14: S43‐S45, 1992.
 132. Kerr AM, Nomura Y, Armstrong D, Anvret M, Belichenko PV, Budden S, Cass H, Christodoulou J, Clarke A, Ellaway C, d'Esposito M, Francke U, Hulten M, Julu P, Leonard H, Naidu S, Schanen C, Webb T, Engerstrom IW, Yamashita Y, Segawa M. Guidelines for reporting clinical features in cases with MECP2 mutations. Brain Dev 23: 208‐211, 2001.
 133. Kline DD, Ogier M, Kunze DL, Katz DM. Exogenous brain‐derived neurotrophic factor rescues synaptic dysfunction in Mecp2‐null mice. J Neurosci 30: 5303‐5310, 2010.
 134. Kozlov SV, Bogenpohl JW, Howell MP, Wevrick R, Panda S, Hogenesch JB, Muglia LJ, Van Gelder RN, Herzog ED, Stewart CL. The imprinted gene Magel2 regulates normal circadian output. Nat Genet 39: 1266‐1272, 2007.
 135. Kron M, Reuter J, Gerhardt E, Manzke T, Zhang W, Dutschmann M. Emergence of brain‐derived neurotrophic factor‐induced postsynaptic potentiation of NMDA currents during the postnatal maturation of the Kolliker‐Fuse nucleus of rat. J Physiol 586: 2331‐2343, 2008.
 136. Kumar R, Ahdout R, Macey PM, Woo MA, Avedissian C, Thompson PM, Harper RM. Reduced caudate nuclei volumes in patients with congenital central hypoventilation syndrome. Neuroscience 163: 1373‐1379, 2009.
 137. Kumar R, Macey PM, Woo MA, Alger JR, Harper RM. Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome. Pediatr Res 64: 275‐280, 2008.
 138. Kumar R, Macey PM, Woo MA, Harper RM. Rostral brain axonal injury in congenital central hypoventilation syndrome. J Neurosci Res 88: 2146‐2154, 2010.
 139. Kumar R, Macey PM, Woo MA, Harper RM. Selectively diminished corpus callosum fibers in congenital central hypoventilation syndrome. Neuroscience 178: 261‐269, 2011.
 140. Kuwaki T, Cao WH, Kurihara Y, Kurihara H, Ling GY, Onodera M, Ju KH, Yazaki Y, Kumada M. Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin‐1. Am J Physiol 270: R1279‐R1286, 1996.
 141. Kuwaki T, Ling GY, Onodera M, Ishii T, Nakamura A, Ju KH, Cao WH, Kumada M, Kurihara H, Kurihara Y, Yazaki Y, Ohuchi T, Yanagisawa M, Fukuda Y. Endothelin in the central control of cardiovascular and respiratory functions. Clin Exp Pharmacol Physiol 26: 989‐994, 1999.
 142. Kwon MJ, Lee GH, Lee MK, Kim JY, Yoo HS, Ki CS, Chang YS, Kim JW, Park WS. PHOX2B mutations in patients with Ondine‐Hirschsprung disease and a review of the literature. Eur J Pediatr 170: 1267‐1271, 2011.
 143. Larimore JL, Chapleau CA, Kudo S, Theibert A, Percy AK, Pozzo‐Miller L. Bdnf overexpression in hippocampal neurons prevents dendritic atrophy caused by Rett‐associated MECP2 mutations. Neurobiol Dis 34: 199‐211, 2009.
 144. Lauterborn JC, Lynch G, Vanderklish P, Arai A, Gall CM. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 20: 8‐21, 2000.
 145. Lee S, Kozlov S, Hernandez L, Chamberlain SJ, Brannan CI, Stewart CL, Wevrick R. Expression and imprinting of MAGEL2 suggest a role in Prader‐Willi syndrome and the homologous murine imprinting phenotype. Hum Mol Genet 9: 1813‐1819, 2000.
 146. Lee S, Walker CL, Karten B, Kuny SL, Tennese AA, O'Neill MA, Wevrick R. Essential role for the Prader‐Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 14: 627‐637, 2005.
 147. Lee S, Walker CL, Wevrick R. Prader‐Willi syndrome transcripts are expressed in phenotypically significant regions of the developing mouse brain. Gene Expr Patterns 3: 599‐609, 2003.
 148. Lekman A, Witt‐Engerstrom I, Gottfries J, Hagberg BA, Percy AK, Svennerholm L. Rett syndrome: Biogenic amines and metabolites in postmortem brain. Pediatr Neurol 5: 357‐362, 1989.
 149. Lekman A, Witt‐Engerstrom I, Holmberg B, Percy A, Svennerholm L, Hagberg B. CSF and urine biogenic amine metabolites in Rett syndrome. Clin Genet 37: 173‐178, 1990.
 150. Lindgren A. Prader‐Willi syndrome and growth hormone teatment. In: Ranke M, Price D, O'Reiter E, editors. Growth Hormone Therapy in ediatrics: 20 Years if KIGS, Basel: Karger, 2007, pp. 309‐376.
 151. Lindgren AC, Hellstrom LG, Ritzen EM, Milerad J. Growth hormone treatment increases CO(2) response, ventilation and central inspiratory drive in children with Prader‐Willi syndrome. Eur J Pediatr 158: 936‐940, 1999.
 152. Livingston FR, Arens R, Bailey SL, Keens TG, Ward SL. Hypercapnic arousal responses in Prader‐Willi syndrome. Chest 108: 1627‐1631, 1995.
 153. Lo L, Morin X, Brunet JF, Anderson DJ. Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells. Neuron 22: 693‐705, 1999.
 154. Lo L, Sommer L, Anderson DJ. MASH1 maintains competence for BMP2‐induced neuronal differentiation in post‐migratory neural crest cells. Curr Biol 7: 440‐450, 1997.
 155. Lotan M. Alternative therapeutic intervention for individuals with Rett syndrome. ScientificWorldJournal 7: 698‐714, 2007.
 156. Lotan M. Assistive technology and supplementary treatment for individuals with Rett syndrome. ScientificWorldJournal 7: 903‐948, 2007.
 157. Lucas ME, Muller F, Rudiger R, Henion PD, Rohrer H. The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons. Development 133: 4015‐4024, 2006.
 158. Lugaresi E, Cirignotta F, Montagna P. Abnormal breathing in the Rett syndrome. Brain Dev 7: 329‐333, 1985.
 159. Maezawa I, Swanberg S, Harvey D, LaSalle JM, Jin LW. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 29: 5051‐5061, 2009.
 160. Marazita ML, Maher BS, Cooper ME, Silvestri JM, Huffman AD, Smok‐Pearsall SM, Kowal MH, Weese‐Mayer DE. Genetic segregation analysis of autonomic nervous system dysfunction in families of probands with idiopathic congenital central hypoventilation syndrome. Am J Med Genet 100: 229‐236, 2001.
 161. Marcus CL, Jansen MT, Poulsen MK, Keens SE, Nield TA, Lipsker LE, Keens TG. Medical and psychosocial outcome of children with congenital central hypoventilation syndrome. J Pediatr 119: 888‐895, 1991.
 162. Matera I, Bachetti T, Puppo F, Di Duca M, Morandi F, Casiraghi G, Cilio M, Hennekam R, Hofstra R, Schöber J, Ravazzolo R, Ottonello G, Ceccherini I. PHOX2B mutations and polyalanine expansions corellate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset central hypoventilation syndrome. J Med Genet 41: 373‐380, 2004.
 163. Matsuishi T, Nagamitsu S, Yamashita Y, Murakami Y, Kimura A, Sakai T, Shoji H, Kato H, Percy AK. Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome. Ann Neurol 42: 978‐981, 1997.
 164. Medrihan L, Tantalaki E, Aramuni G, Sargsyan V, Dudanova I, Missler M, Zhang W. Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome. J Neurophysiol 99: 112‐121, 2008.
 165. Mellins RB, Balfour HH, Jr., Turino GM, Winters RW. Failure of automatic control of ventilation (Ondine's curse). Report of an infant born with this syndrome and review of the literature. Medicine (Baltimore) 49: 487‐504, 1970.
 166. Mercer RE, Kwolek EM, Bischof JM, van Eede M, Henkelman RM, Wevrick R. Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2. Am J Med Genet B Neuropsychiatr Genet 150B: 1085‐1099, 2009.
 167. Metcalf BM, Mullaney BC, Johnston MV, Blue ME. Temporal shift in methyl‐CpG binding protein 2 expression in a mouse model of Rett syndrome. Neuroscience 139: 1449‐1460, 2006.
 168. Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short‐term effects of growth hormone on sleep abnormalities in Prader‐Willi syndrome. J Clin Endocrinol Metab 91: 413‐417, 2006.
 169. Miller JL, Couch J, Schwenk K, Long M, Towler S, Theriaque DW, He G, Liu Y, Driscoll DJ, Leonard CM. Early childhood obesity is associated with compromised cerebellar development. Dev Neuropsychol 34: 272‐283, 2009.
 170. Miller JL, Couch JA, Schmalfuss I, He G, Liu Y, Driscoll DJ. Intracranial abnormalities detected by three‐dimensional magnetic resonance imaging in Prader‐Willi syndrome. Am J Med Genet A 143: 476‐483, 2007.
 171. Miller JL, Shuster J, Theriaque D, Driscoll DJ, Wagner M. Sleep disordered breathing in infants with Prader‐Willi syndrome during the first 6 weeks of growth hormone therapy: A pilot study. J Clin Sleep Med 5: 448‐453, 2009.
 172. Mironov SL, Skorova E, Hartelt N, Mironova LA, Hasan MT, Kugler S. Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain‐derived neurotrophic factor regulated slow calcium buffering. J Physiol 587: 2473‐2485, 2009.
 173. Monteau R, Ptak K, Broquere N, Hilaire G. Tachykinins and central respiratory activity: An in vitro study on the newborn rat. Eur J Pharmacol 314: 41‐50, 1996.
 174. Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver‐Moore K, Rosenthal A. Renal and neuronal abnormalities in mice lacking GDNF. Nature 382: 76‐79, 1996.
 175. Morin X, Cremer H, Hirsch MR, Kapur RP, Goridis C, Brunet JF. Defects in sensory and autonomic ganglia and absence of locus coeruleus in mice deficient for the homeobox gene Phox2a. Neuron 18: 411‐423, 1997.
 176. Mullaney BC, Johnston MV, Blue ME. Developmental expression of methyl‐CpG binding protein 2 is dynamically regulated in the rodent brain. Neuroscience 123: 939‐949, 2004.
 177. Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H. Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader‐Willi syndrome. Hum Mol Genet 9: 3101‐3110, 2000.
 178. Mutolo D, Bongianni F, Carfi M, Pantaleo T. Respiratory responses to thyrotropin‐releasing hormone microinjected into the rabbit medulla oblongata. Am J Physiol 277: R1331‐R1338, 1999.
 179. Nakada Y, Taniura H, Uetsuki T, Inazawa J, Yoshikawa K. The human chromosomal gene for necdin, a neuronal growth suppressor, in the Prader‐Willi syndrome deletion region. Gene 213: 65‐72, 1998.
 180. Nakamura A, Kuwaki T, Kuriyama T, Yanagisawa M, Fukuda Y. Normal ventilation and ventilatory responses to chemical stimuli in juvenile mutant mice deficient in endothelin‐3. Respir Physiol 124: 1‐9, 2001.
 181. Nattie EE. Central chemosensitivity, sleep, and wakefulness. Respir Physiol 129: 257‐268, 2001.
 182. Nattie EE, Li A. CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep. J Appl Physiol 90: 1247‐1257, 2001.
 183. Nattie EE, Li A. CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness. J Appl Physiol 92: 2119‐2130, 2002.
 184. Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi‐Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK. Rett syndrome: Revised diagnostic criteria and nomenclature. Ann Neurol 68: 944‐950, 2010.
 185. Nicholls RD and Knepper JL. Genome organization, function, and imprinting in Prader‐Willi and Angelman syndromes. Annu Rev Genomics Hum Genet 2: 153‐175, 2001.
 186. Nink M, Krause U, Lehnert H, Heuberger W, Huber I, Schulz R, Hommel G, Beyer J. Thyrotropin‐releasing hormone has stimulatory effects on ventilation in humans. Acta Physiol Scand 141: 309‐318, 1991.
 187. Nissenkorn A, Gak E, Vecksler M, Reznik H, Menascu S, Ben Zeev B. Epilepsy in Rett syndrome‐The experience of a National Rett Center. Epilepsia 51: 1252‐1258, 2010.
 188. Nixon GM, Brouillette RT. Sleep and breathing in Prader‐Willi syndrome. Pediatr Pulmonol 34: 209‐217, 2002.
 189. Ogier M, Katz DM. Breathing dysfunction in Rett syndrome: Understanding epigenetic regulation of the respiratory network. Respir Physiol Neurobiol 164: 55‐63, 2008.
 190. Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain‐derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 27: 10912‐10917, 2007.
 191. Ogren JA, Macey PM, Kumar R, Woo MA, Harper RM. Central autonomic regulation in congenital central hypoventilation syndrome. Neuroscience 167: 1249‐1256, 2010.
 192. Onimaru H, Homma I. A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J Neurosci 23: 1478‐1486, 2003.
 193. Oren J, Kelly DH, Shannon DC. Long‐term follow‐up of children with congenital central hypoventilation syndrome. Pediatrics 80: 375‐380, 1987.
 194. Orenstein DM, Boat TF, Owens RP, Horowitz JG, Primiano FP, Jr., Germann K, Doershuk CF. The obesity hypoventilation syndrome in children with the Prader‐Willi syndrome: A possible role for familial decreased response to carbon dioxide. J Pediatr 97: 765‐767, 1980.
 195. Pagliardini S, Ren J, Wevrick R, Greer JJ. Developmental abnormalities of neuronal structure and function in prenatal mice lacking the prader‐willi syndrome gene necdin. Am J Pathol 167: 175‐191, 2005.
 196. Pagliardini S, Rent J, Wevrick R, Greer JJ. Neurodevelopmental abnormalities in the brainstem of prenatal mice lacking the Prader‐Willi syndrome gene Necdin. Adv Exp Med Biol 605: 139‐143, 2008.
 197. Palmer A, Qayumi J, Ronnett G. MeCP2 mutation causes distinguishable phases of acute and chronic defects in synaptogenesis and maintenance, respectively. Mol Cell Neurosci 37: 794‐807, 2008.
 198. Paterson DS, Thompson EG, Belliveau RA, Antalffy BA, Trachtenberg FL, Armstrong DD, Kinney HC. Serotonin transporter abnormality in the dorsal motor nucleus of the vagus in Rett syndrome: Potential implications for clinical autonomic dysfunction. J Neuropathol Exp Neurol 64: 1018‐1027, 2005.
 199. Paton JY, Swaminathan S, Sargent CW, Hawksworth A, Keens TG. Ventilatory response to exercise in children with congenital central hypoventilation syndrome. Am Rev Respir Dis 147: 1185‐1191, 1993.
 200. Paton JY, Swaminathan S, Sargent CW, Keens TG. Hypoxic and hypercapnic ventilatory responses in awake children with congenital central hypoventilation syndrome. Am Rev Respir Dis 140: 368‐372, 1989.
 201. Pattyn A, Goridis C, Brunet JF. Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Mol Cell Neurosci 15: 235‐243, 2000.
 202. Pattyn A, Hirsch M, Goridis C, Brunet JF. Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development 127: 1349‐1358, 2000.
 203. Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF. Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development 124: 4065‐4075, 1997.
 204. Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399: 366‐370, 1999.
 205. Patwari PP, Carroll MS, Rand CM, Kumar R, Harper R, Weese‐Mayer DE. Congenital central hypoventilation syndrome and the PHOX2B gene: A model of respiratory and autonomic dysregulation. Respir Physiol Neurobiol 173: 322‐335, 2010.
 206. Pelka GJ, Watson CM, Radziewic T, Hayward M, Lahooti H, Christodoulou J, Tam PP. Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice. Brain 129: 887‐898, 2006.
 207. Pena F, Ramirez JM. Substance P‐mediated modulation of pacemaker properties in the mammalian respiratory network. J Neurosci 24: 7549‐7556, 2004.
 208. Percy AK. Clinical trials and treatment prospects. Ment Retard Dev Disabil Res Rev 8: 106‐111, 2002.
 209. Percy AK. Rett syndrome: Recent research progress. J Child Neurol 23: 543‐549, 2008.
 210. Percy AK, Glaze DG, Schultz RJ, Zoghbi HY, Williamson D, Frost JD, Jr., Jankovic JJ, del Junco D, Skender M, Waring S, et al. Rett syndrome: Controlled study of an oral opiate antagonist, naltrexone. Ann Neurol 35: 464‐470, 1994.
 211. Percy AK, Lane JB, Childers J, Skinner S, Annese F, Barrish J, Caeg E, Glaze DG, MacLeod P. Rett syndrome: North American database. J Child Neurol 22: 1338‐1341, 2007.
 212. Poceta JS, Strandjord TP, Badura RJ, Jr., Milstein JM. Ondine curse and neurocristopathy. Pediatr Neurol 3: 370‐372, 1987.
 213. Prader A, Labhart A, Willi H. Ein syndrom von adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach myatonieartigem zustandim neugeborenenalter. Schweiz Med Wochenschr 86: 1260‐1261, 1956.
 214. Preston ME, Jensen D, Janssen I, Fisher JT. Effect of menopause on the chemical control of breathing and its relationship with acid‐base status. Am J Physiol Regul Integr Comp Physiol 296: R722‐R727, 2009.
 215. Ptak K, Burnet H, Blanchi B, Sieweke M, De Felipe C, Hunt SP, Monteau R, Hilaire G. The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation. Eur J Neurosci 16: 2245‐2252, 2002.
 216. Ptak K, Di Pasquale E, Monteau R. Substance P and central respiratory activity: A comparative in vitro study on foetal and newborn rat. Brain Res Dev Brain Res 114: 217‐227, 1999.
 217. Ptak K, Konrad M, Di Pasquale E, Tell F, Hilaire G, Monteau R. Cellular and synaptic effect of substance P on neonatal phrenic motoneurons. Eur J Neurosci 12: 126‐138, 2000.
 218. Ramanantsoa N, Vaubourg V, Dauger S, Matrot B, Vardon G, Chettouh Z, Gaultier C, Goridis C, Gallego J. Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factor Phox2b. Am J Physiol Regul Integr Comp Physiol 290: R1691‐1696, 2006.
 219. Ramanantsoa N, Vaubourg V, Matrot B, Vardon G, Dauger S, Gallego J. Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. Am J Physiol Regul Integr Comp Physiol 293: R2027‐R2035, 2007.
 220. Ramirez JM, Viemari JC. Determinants of inspiratory activity. Respir Physiol Neurobiol 147: 145‐157, 2005.
 221. Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN, Moser H. Neuroanatomy of Rett syndrome: A volumetric imaging study. Ann Neurol 34: 227‐234, 1993.
 222. Ren J, Lee S, Pagliardini S, Gerard M, Stewart CL, Greer JJ, Wevrick R. Absence of Ndn, encoding the Prader‐Willi syndrome‐deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice. J Neurosci 23: 1569‐1573, 2003.
 223. Ren J, Poon BY, Tang Y, Funk GD, Greer JJ. Ampakines alleviate respiratory depression in rats. Am J Respir Crit Care Med 174: 1384‐1391, 2006.
 224. Renolleau S, Dauger S, Vardon G, Levacher B, Simonneau M, Yanagisawa M, Gaultier C, Gallego J. Impaired ventilatory responses to hypoxia in mice deficient in endothelin‐converting‐enzyme‐1. Pediatr Res 49: 705‐712, 2001.
 225. Rett A. [On a unusual brain atrophy syndrome in hyperammonemia in childhood]. Wien Med Wochenschr 116: 723‐726, 1966.
 226. Ricceri L, De Filippis B, Laviola G. Mouse models of Rett syndrome: From behavioural phenotyping to preclinical evaluation of new therapeutic approaches. Behav Pharmacol 19: 501‐517, 2008.
 227. Rohdin M, Fernell E, Eriksson M, Albage M, Lagercrantz H, Katz‐Salamon M. Disturbances in cardiorespiratory function during day and night in Rett syndrome. Pediatr Neurol 37: 338‐344, 2007.
 228. Roux JC, Dura E, Moncla A, Mancini J, Villard L. Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome. Eur J Neurosci 25: 1915‐1922, 2007.
 229. Roux JC, Dura E, Villard L. Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse. Neurosci Lett 447: 82‐86, 2008.
 230. Roux JC, Villard L. Biogenic amines in Rett syndrome: The usual suspects. Behav Genet 40: 59‐75, 2010.
 231. Rudzinski E, Kapur RP. PHOX2B immunolocalization of the candidate human retrotrapezoid nucleus. Pediatr Dev Pathol 13: 291‐299, 2010.
 232. Ruggiero DA, Gootman PM, Ingenito S, Wong C, Gootman N, Sica AL. The area postrema of newborn swine is activated by hypercapnia: Relevance to sudden infant death syndrome? J Auton Nerv Syst 76: 167‐175, 1999.
 233. Saito Y, Ito M, Ozawa Y, Matsuishi T, Hamano K, Takashima S. Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome. Brain Dev 23(Suppl 1): S122‐S126, 2001.
 234. Samaco RC, Fryer JD, Ren J, Fyffe S, Chao HT, Sun Y, Greer JJ, Zoghbi HY, Neul JL. A partial loss of function allele of methyl‐CpG‐binding protein 2 predicts a human neurodevelopmental syndrome. Hum Mol Genet 17: 1718‐1727, 2008.
 235. Santos M, Silva‐Fernandes A, Oliveira P, Sousa N, Maciel P. Evidence for abnormal early development in a mouse model of Rett syndrome. Genes Brain Behav 6: 277‐286, 2007.
 236. Sasaki A, Kanai M, Kijima K, Akaba K, Hashimoto M, Hasegawa H, Otaki S, Koizumi T, Kusuda S, Ogawa Y, Tuchiya K, Yamamoto W, Nakamura T, Hayasaka K. Molecular analysis of congenital central hypoventilation syndrome. Hum Genet 114: 22‐26, 2003.
 237. Schluter B, Buschatz D, Trowitzsch E, Aksu F, Andler W. Respiratory control in children with Prader‐Willi syndrome. Eur J Pediatr 156: 65‐68, 1997.
 238. Schulz R, Nink M, Werner GS, Andreas S, Kreuzer H, Beyer J, Lehnert H. Human corticotropin‐releasing hormone and thyrotropin‐releasing hormone modulate the hypercapnic ventilatory response in humans. Eur J Clin Invest 26: 989‐995, 1996.
 239. Serra A, Gorgens H, Alhadad K, Fitze G, Schackert HK. Analysis of RET, ZEB2, EDN3 and GDNF genomic rearrangements in central congenital hyperventilation syndrome patients by multiplex ligation‐dependent probe amplification. Ann Hum Genet 74: 369‐374, 2010.
 240. Shahbazian M, Young J, Yuva‐Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35: 243‐254, 2002.
 241. Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. Insight into Rett syndrome: MeCP2 levels display tissue‐ and cell‐specific differences and correlate with neuronal maturation. Hum Mol Genet 11: 115‐124, 2002.
 242. Shea SA, Andres LP, Shannon DC, Banzett RB. Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity. J Physiol 468: 623‐640, 1993.
 243. Shvarev YN, Lagercrantz H. Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P. Eur J Neurosci 24: 2253‐2263, 2006.
 244. Silvestri JM, Weese‐Mayer DE, Flanagan EA. Congenital central hypoventilation syndrome: Cardiorespiratory responses to moderate exercise, simulating daily activity. Pediatr Pulmonol 20: 89‐93, 1995.
 245. Silvestri JM, Weese‐Mayer DE, Nelson MN. Neuropsychologic abnormalities in children with congenital central hypoventilation syndrome. J Pediatr 120: 388‐393, 1992.
 246. Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ, Andrews R, Bird AP. Neuronal MeCP2 is expressed at near histone‐octamer levels and globally alters the chromatin state. Mol Cell 37: 457‐468, 2010.
 247. Smeets EE, Julu PO, van Waardenburg D, Engerstrom IW, Hansen S, Apartopoulos F, Curfs LM, Schrander‐Stumpel CT. Management of a severe forceful breather with Rett syndrome using carbogen. Brain Dev 28: 625‐632, 2006.
 248. Smith A, Egan J, Ridley G, Haan E, Montgomery P, Williams K, Elliott E. Birth prevalence of Prader‐Willi syndrome in Australia. Arch Dis Child 88: 263‐264, 2003.
 249. Smith JC, Morrison DE, Ellenberger HH, Otto MR, Feldman JL. Brainstem projections to the major respiratory neuron populations in the medulla of the cat. J Comp Neurol 281: 69‐96, 1989.
 250. Sommer L, Shah N, Rao M, Anderson DJ. The cellular function of MASH1 in autonomic neurogenesis. Neuron 15: 1245‐1258, 1995.
 251. Southall DP, Kerr AM, Tirosh E, Amos P, Lang MH, Stephenson JB. Hyperventilation in the awake state: Potentially treatable component of Rett syndrome. Arch Dis Child 63: 1039‐1048, 1988.
 252. Spengler CM, Banzett RB, Systrom DM, Shannon DC, Shea SA. Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity. Respir Physiol 114: 65‐74, 1998.
 253. Sritippayawan S, Hamutcu R, Kun SS, Ner Z, Ponce M, Keens TG. Mother‐daughter transmission of congenital central hypoventilation syndrome. Am J Respir Crit Care Med 166: 367‐369, 2002.
 254. Stafler P and Wallis C. Prader‐Willi syndrome: Who can have growth hormone? Arch Dis Child 93: 341‐345, 2008.
 255. Stearns NA, Schaevitz LR, Bowling H, Nag N, Berger UV, Berger‐Sweeney J. Behavioral and anatomical abnormalities in Mecp2 mutant mice: A model for Rett syndrome. Neuroscience 146: 907‐921, 2007.
 256. Stettner GM, Huppke P, Brendel C, Richter DW, Gartner J, Dutschmann M. Breathing dysfunctions associated with impaired control of postinspiratory activity in Mecp2‐/y knockout mice. J Physiol 579: 863‐876, 2007.
 257. Stettner GM, Huppke P, Gartner J, Richter DW, Dutschmann M. Disturbances of breathing in Rett syndrome: Results from patients and animal models. Adv Exp Med Biol 605: 503‐507, 2008.
 258. Stornetta RL, Moreira TS, Takakura AC, Kang BJ, Chang DA, West GH, Brunet JF, Mulkey DK, Bayliss DA, Guyenet PG. Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. J Neurosci 26: 10305‐10314, 2006.
 259. Straus C, Trang H, Becquemin MH, Touraine P, Similowski T. Chemosensitivity recovery in Ondine's curse syndrome under treatment with desogestrel. Respir Physiol Neurobiol 171: 171‐174, 2010.
 260. Sun YE, Wu H. The ups and downs of BDNF in Rett syndrome. Neuron 49: 321‐323, 2006.
 261. Taddeucci G, Bonuccelli A, Mantellassi I, Orsini A, Tarantino E. Pitt‐Hopkins syndrome: Report of a case with a TCF4 gene mutation. Ital J Pediatr 36: 12, 2010.
 262. Tauber M, Diene G, Molinas C, Hebert M. Review of 64 cases of death in children with Prader‐Willi syndrome (PWS). Am J Med Genet A 146: 881‐887, 2008.
 263. Temudo T, Rios M, Prior C, Carrilho I, Santos M, Maciel P, Sequeiros J, Fonseca M, Monteiro J, Cabral P, Vieira JP, Ormazabal A, Artuch R. Evaluation of CSF neurotransmitters and folate in 25 patients with rett disorder and effects of treatment. Brain Dev 31: 46‐51, 2009.
 264. Thoby‐Brisson M, Cauli B, Champagnat J, Fortin G, Katz DM. Expression of functional tyrosine kinase B receptors by rhythmically active respiratory neurons in the pre‐Botzinger complex of neonatal mice. J Neurosci 23: 7685‐7689, 2003.
 265. Thoby‐Brisson M, Karlen M, Wu N, Charnay P, Champagnat J, Fortin G. Genetic identification of an embryonic parafacial oscillator coupling to the preBotzinger complex. Nat Neurosci 12: 1028‐1035, 2009.
 266. Tiveron MC, Hirsch MR, Brunet JF. The expression pattern of the transcription factor Phox2 delineates synaptic pathways of the autonomic nervous system. J Neurosci 16: 7649‐7660, 1996.
 267. Trang H. Congenital central hypoventilation syndrome: From patients to gene discovery In: Gaultier C, editor. Genetic Basis for Respiratory Control Disorders. New York: Springer, 2008, pp. 45‐55.
 268. Trang H, Dehan M, Beaufils F, Zaccaria I, Amiel J, Gaultier C. The French congenital central hypoventilation syndrome registry: General data, phenotype, and genotype. Chest 127: 72‐79, 2005.
 269. Trochet D, de Pontual L, Estevao MH, Mathieu Y, Munnich A, Feingold J, Goridis C, Lyonnet S, Amiel J. Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine's Curse). Hum Mutat 29: 770, 2008.
 270. Trochet D, Hong SJ, Lim JK, Brunet JF, Munnich A, Kim KS, Lyonnet S, Goridis C, Amiel J. Molecular consequences of PHOX2B missense, frameshift and alanine expansion mutations leading to autonomic dysfunction. Hum Mol Genet 14: 3697‐3708, 2005.
 271. Trochet D, O'Brien LM, Gozal D, Trang H, Nordenskjold A, Laudier B, Svensson PJ, Uhrig S, Cole T, Niemann S, Munnich A, Gaultier C, Lyonnet S, Amiel J. PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome. Am J Hum Genet 76: 421‐426, 2005.
 272. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. Partial reversal of Rett syndrome‐like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 106: 2029‐2034, 2009.
 273. Tsai TF, Armstrong D, Beaudet AL. Necdin‐deficient mice do not show lethality or the obesity and infertility of Prader‐Willi syndrome. Nat Genet 22: 15‐16, 1999.
 274. Tupal S, Faingold CL. Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice. Epilepsia 47: 21‐26, 2006.
 275. Uteshev VV, Tupal S, Mhaskar Y, Faingold CL. Abnormal serotonin receptor expression in DBA/2 mice associated with susceptibility to sudden death due to respiratory arrest. Epilepsy Res 88: 183‐188, 2010.
 276. Vanderlaan M, Holbrook CR, Wang M, Tuell A, Gozal D. Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome. Pediatr Pulmonol 37: 217‐229, 2004.
 277. Viemari JC, Bevengut M, Burnet H, Coulon P, Pequignot JM, Tiveron MC, Hilaire G. Phox2a gene, A6 neurons, and noradrenaline are essential for development of normal respiratory rhythm in mice. J Neurosci 24: 928‐937, 2004.
 278. Viemari JC, Maussion G, Bevengut M, Burnet H, Pequignot JM, Nepote V, Pachnis V, Simonneau M, Hilaire G. Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythm. Eur J Neurosci 22: 2403‐2412, 2005.
 279. Viemari JC, Ramirez JM. Norepinephrine differentially modulates different types of respiratory pacemaker and nonpacemaker neurons. J Neurophysiol 95: 2070‐2082, 2006.
 280. Viemari JC, Roux JC, Tryba AK, Saywell V, Burnet H, Pena F, Zanella S, Bevengut M, Barthelemy‐Requin M, Herzing LB, Moncla A, Mancini J, Ramirez JM, Villard L, Hilaire G. Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 25: 11521‐11530, 2005.
 281. Voituron N, Zanella S, Menuet C, Dutschmann M, Hilaire G. Early breathing defects after moderate hypoxia or hypercapnia in a mouse model of Rett syndrome. Respir Physiol Neurobiol 168: 109‐118, 2009.
 282. Voituron N, Zanella S, Menuet C, Lajard AM, Dutschmann M, Hilaire G. Early abnormalities of post‐sigh breathing in a mouse model of Rett syndrome. Respir Physiol Neurobiol 170: 173‐182, 2010.
 283. Wang H, Chan SA, Ogier M, Hellard D, Wang Q, Smith C, Katz DM. Dysregulation of brain‐derived neurotrophic factor expression and neurosecretory function in Mecp2 null mice. J Neurosci 26: 10911‐10915, 2006.
 284. Ward BC, Agarwal S, Wang K, Berger‐Sweeney J, Kolodny NH. Longitudinal brain MRI study in a mouse model of Rett Syndrome and the effects of choline. Neurobiol Dis 31: 110‐119, 2008.
 285. Ward BC, Kolodny NH, Nag N, Berger‐Sweeney JE. Neurochemical changes in a mouse model of Rett syndrome: Changes over time and in response to perinatal choline nutritional supplementation. J Neurochem 108: 361‐371, 2009.
 286. Watson CM, Pelka GJ, Radziewic T, Shahbazian MD, Christodoulou J, Williamson SL, Tam PP. Reduced proportion of purkinje cells expressing paternally derived mutant Mecp2308 allele in female mouse cerebellum is not due to a skewed primary pattern of X‐chromosome inactivation. Hum Mol Genet 14: 1851‐1861, 2005.
 287. Weaving LS, Ellaway CJ, Gecz J, Christodoulou J. Rett syndrome: Clinical review and genetic update. J Med Genet 42: 1‐7, 2005.
 288. Weese‐Mayer D, Berry‐Kravis E, Zhou L. Adult identified with congenital central hypoventilation syndrome–mutation in PHOX2b gene and late‐onset CHS Am J Respir Crit Care Med 171: 88, 2005.
 289. Weese‐Mayer D, Marazita M, Berry‐Kravis E. Congenital central hypoventilation syndrome. In: Pagon R, Bird T, Dolan C, Stephens K, edirors. GeneReviews (Internet), Seattle (WA): University of Washington, 2008
 290. Weese‐Mayer D, Shannon DC, Keens TG, Silvestri JM. Idiopathic congenital central hypoventilation syndrome: Diagnosis and management. American Thoracic Society. Am J Respir Crit Care Med 160: 368‐373, 1999.
 291. Weese‐Mayer DE, Berry‐Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H. An official ATS clinical policy statement: Congenital central hypoventilation syndrome: Genetic basis, diagnosis, and management. Am J Respir Crit Care Med 181: 626‐644, 2010.
 292. Weese‐Mayer DE, Berry‐Kravis EM, Ceccherini I, Rand CM. Congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS): Kindred disorders of autonomic regulation. Respir Physiol Neurobiol 164: 38‐48, 2008.
 293. Weese‐Mayer DE, Berry‐Kravis EM, Marazita ML. In pursuit (and discovery) of a genetic basis for congenital central hypoventilation syndrome. Respir Physiol Neurobiol 142: 73‐82, 2005.
 294. Weese‐Mayer DE, Berry‐Kravis EM, Zhou L, Maher BS, Silvestri JM, Curran ME, Marazita ML. Idiopathic congenital central hypoventilation syndrome: Analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b. Am J Med Genet 123A: 267‐278, 2003.
 295. Weese‐Mayer DE, Bolk S, Silvestri JM, Chakravarti A. Idiopathic congenital central hypoventilation syndrome: Evaluation of brain‐derived neurotrophic factor genomic DNA sequence variation. Am J Med Genet 107: 306‐310, 2002.
 296. Weese‐Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Ramirez JM. Autonomic dysregulation in young girls with Rett syndrome during nighttime in‐home recordings. Pediatr Pulmonol 43: 1045‐1060, 2008.
 297. Weese‐Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Silvestri JM, Ramirez JM. Autonomic nervous system dysregulation: Breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr Res 60: 443‐449, 2006.
 298. Weese‐Mayer DE, Rand CM, Berry‐Kravis EM, Jennings LJ, Loghmanee DA, Patwari PP, Ceccherini I. Congenital central hypoventilation syndrome from past to future: Model for translational and transitional autonomic medicine. Pediatr Pulmonol 44: 521‐535, 2009.
 299. Weese‐Mayer DE, Silvestri JM, Huffman AD, Smok‐Pearsall SM, Kowal MH, Maher BS, Cooper ME, Marazita ML. Case/control family study of autonomic nervous system dysfunction in idiopathic congenital central hypoventilation syndrome. Am J Med Genet 100: 237‐245, 2001.
 300. Wenk GL. Rett syndrome: Neurobiological changes underlying specific symptoms. Prog Neurobiol 51: 383‐391, 1997.
 301. Woo MA, Macey PM, Macey KE, Keens TG, Woo MS, Harper RK, Harper RM. FMRI responses to hyperoxia in congenital central hypoventilation syndrome. Pediatr Res 57: 510‐518, 2005.
 302. Yamada K, Matsuzawa H, Uchiyama M, Kwee IL, Nakada T. Brain developmental abnormalities in Prader‐Willi syndrome detected by diffusion tensor imaging. Pediatrics 118: e442‐448, 2006.
 303. Yanagisawa H, Yanagisawa M, Kapur RP, Richardson JA, Williams SC, Clouthier DE, de Wit D, Emoto N, Hammer RE. Dual genetic pathways of endothelin‐mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme‐1 gene. Development 125: 825‐836, 1998.
 304. Yee BJ, Buchanan PR, Mahadev S, Banerjee D, Liu PY, Phillips C, Loughnan G, Steinbeck K, Grunstein RR. Assessment of sleep and breathing in adults with prader‐willi syndrome: A case control series. J Clin Sleep Med 3: 713‐718, 2007.
 305. Zanella S, Mebarek S, Lajard AM, Picard N, Dutschmann M, Hilaire G. Oral treatment with desipramine improves breathing and life span in Rett syndrome mouse model. Respir Physiol Neurobiol 160: 116‐121, 2008.
 306. Zanella S, Tauber M, Muscatelli F. Breathing deficits of the Prader‐Willi syndrome. Respir Physiol Neurobiol 168: 119‐124, 2009.
 307. Zanella S, Watrin F, Mebarek S, Marly F, Roussel M, Gire C, Diene G, Tauber M, Muscatelli F, Hilaire G. Necdin plays a role in the serotonergic modulation of the mouse respiratory network: Implication for Prader‐Willi syndrome. J Neurosci 28: 1745‐1755, 2008.
 308. Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecsler M, Christodoulou J. The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome. Neurology 72: 1242‐1247, 2009.
 309. Zelko FA, Nelson MN, Leurgans SE, Berry‐Kravis EM, Weese‐Mayer DE. Congenital central hypoventilation syndrome: Neurocognitive functioning in school age children. Pediatr Pulmonol 45: 92‐98, 2010.
 310. Zweier C, Sticht H, Bijlsma EK, Clayton‐Smith J, Boonen SE, Fryer A, Greally MT, Hoffmann L, den Hollander NS, Jongmans M, Kant SG, King MD, Lynch SA, McKee S, Midro AT, Park SM, Ricotti V, Tarantino E, Wessels M, Peippo M, Rauch A. Further delineation of Pitt‐Hopkins syndrome: Phenotypic and genotypic description of 16 novel patients. J Med Genet 45: 738‐744, 2008.

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Jorge Gallego. Genetic Diseases: Congenital Central Hypoventilation, Rett, and Prader‐Willi Syndromes. Compr Physiol 2012, 2: 2255-2279. doi: 10.1002/cphy.c100037