{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:52:16Z","timestamp":1784717536649,"version":"3.55.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T00:00:00Z","timestamp":1256083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T00:00:00Z","timestamp":1256083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2010,2]]},"DOI":"10.1007\/s00401-009-0599-8","type":"journal-article","created":{"date-parts":[[2009,10,20]],"date-time":"2009-10-20T19:42:18Z","timestamp":1256067738000},"page":"261-269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Novel neuropathologic findings in the Haddad syndrome"],"prefix":"10.1007","volume":"119","author":[{"given":"Nestor D.","family":"Tomycz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith F.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Ackerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Kinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,10,21]]},"reference":[{"key":"599_CR1","doi-asserted-by":"crossref","unstructured":"(1999) Idiopathic congenital central hypoventilation syndrome: diagnosis and management. American Thoracic Society. Am J Respir Crit Care Med 160:368-373","DOI":"10.1164\/ajrccm.160.1.16010"},{"key":"599_CR2","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/S0306-4522(02)00484-0","volume":"115","author":"C Alvarez","year":"2002","unstructured":"Alvarez C, Vitalis T, Fon EA et al (2002) Effects of genetic depletion of monoamines on somatosensory cortical development. Neuroscience 115:753\u2013764","journal-title":"Neuroscience"},{"key":"599_CR3","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/ng1130","volume":"33","author":"J Amiel","year":"2003","unstructured":"Amiel J, Laudier B, Attie-Bitach T et al (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33:459\u2013461","journal-title":"Nat Genet"},{"key":"599_CR4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/ana.410120207","volume":"12","author":"D Armstrong","year":"1982","unstructured":"Armstrong D, Sachis P, Bryan C, Becker L (1982) Pathological features of persistent infantile sleep apnea with reference to the pathology of sudden infant death syndrome. Ann Neurol 12:169\u2013174","journal-title":"Ann Neurol"},{"key":"599_CR5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1055\/s-2008-1052538","volume":"16","author":"LE Becker","year":"1985","unstructured":"Becker LE, Takashima S (1985) Chronic hypoventilation and development of brain stem gliosis. Neuropediatrics 16:19\u201323","journal-title":"Neuropediatrics"},{"key":"599_CR6","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1007\/s00401-008-0351-9","volume":"115","author":"EE Benarroch","year":"2008","unstructured":"Benarroch EE, Schmeichel AM, Low PA, Sandroni P, Parisi JE (2008) Loss of A5 noradrenergic neurons in multiple system atrophy. Acta Neuropathol 115:629\u2013634","journal-title":"Acta Neuropathol"},{"key":"599_CR7","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s00424-007-0338-8","volume":"455","author":"V Biancardi","year":"2008","unstructured":"Biancardi V, Bicego KC, Almeida MC, Gargaglioni LH (2008) Locus coeruleus noradrenergic neurons and CO2 drive to breathing. Pflugers Arch 455:1119\u20131128","journal-title":"Pflugers Arch"},{"key":"599_CR8","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/BF02723168","volume":"70","author":"S D\u2019Souza","year":"2003","unstructured":"D\u2019Souza S, Khubchandani RP (2003) Haddad syndrome\u2014congenital central hypoventilation associated with Hirschsprung\u2019s disease. Indian J Pediatr 70:597\u2013599","journal-title":"Indian J Pediatr"},{"key":"599_CR9","doi-asserted-by":"publisher","first-page":"6635","DOI":"10.1242\/dev.00866","volume":"130","author":"S Dauger","year":"2003","unstructured":"Dauger S, Pattyn A, Lofaso F et al (2003) Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways. Development 130:6635\u20136642","journal-title":"Development"},{"key":"599_CR10","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1073\/pnas.0709115105","volume":"105","author":"V Dubreuil","year":"2008","unstructured":"Dubreuil V, Ramanantsoa N, Trochet D et al (2008) A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons. Proc Natl Acad Sci USA 105:1067\u20131072","journal-title":"Proc Natl Acad Sci USA"},{"key":"599_CR11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/aja.1000130103","volume":"13","author":"C Essick","year":"1912","unstructured":"Essick C (1912) The development of the nucleus pontis and nucleus arcuatus in man. Am J Anat 13:25\u201354","journal-title":"Am J Anat"},{"key":"599_CR12","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/cne.902930308","volume":"293","author":"JJ Filiano","year":"1990","unstructured":"Filiano JJ, Choi JC, Kinney HC (1990) Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. J Comp Neurol 293:448\u2013465","journal-title":"J Comp Neurol"},{"key":"599_CR13","first-page":"659","volume":"15","author":"H Folgering","year":"1979","unstructured":"Folgering H, Kuyper F, Kille JF (1979) Primary alveolar hypoventilation (Ondine\u2019s curse syndrome) in an infant without external arcuate nucleus. Case report. Bull Eur Physiopathol Respir 15:659\u2013665","journal-title":"Bull Eur Physiopathol Respir"},{"key":"599_CR14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3928\/0191-3913-19960501-11","volume":"33","author":"DS Goldberg","year":"1996","unstructured":"Goldberg DS, Ludwig IH (1996) Congenital central hypoventilation syndrome: ocular findings in 37 children. J Pediatr Ophthalmol Strabismus 33:175\u2013180","journal-title":"J Pediatr Ophthalmol Strabismus"},{"key":"599_CR15","doi-asserted-by":"publisher","first-page":"8938","DOI":"10.1523\/JNEUROSCI.2415-05.2005","volume":"25","author":"PG Guyenet","year":"2005","unstructured":"Guyenet PG, Mulkey DK, Stornetta RL, Bayliss DA (2005) Regulation of ventral surface chemoreceptors by the central respiratory pattern generator. J Neurosci 25:8938\u20138947","journal-title":"J Neurosci"},{"key":"599_CR16","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1113\/jphysiol.2008.150870","volume":"586","author":"PG Guyenet","year":"2008","unstructured":"Guyenet PG, Stornetta RL, Bayliss DA (2008) Retrotrapezoid nucleus and central chemoreception. J Physiol 586:2043\u20132048","journal-title":"J Physiol"},{"key":"599_CR17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/00005792-197811000-00003","volume":"57","author":"GG Haddad","year":"1978","unstructured":"Haddad GG, Mazza NM, Defendini R et al (1978) Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate. Medicine (Baltimore) 57:517\u2013526","journal-title":"Medicine (Baltimore)"},{"key":"599_CR18","first-page":"3","volume":"87","author":"Y Kayama","year":"2003","unstructured":"Kayama Y, Koyama Y (2003) Control of sleep and wakefulness by brainstem monoaminergic and cholinergic neurons. Acta Neurochir Suppl 87:3\u20136","journal-title":"Acta Neurochir Suppl"},{"key":"599_CR19","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1097\/00005072-198805000-00003","volume":"47","author":"HC Kinney","year":"1988","unstructured":"Kinney HC, Brody BA, Kloman AS, Gilles FH (1988) Sequence of CNS myelination in human infancy II. Patterns of myelination in autopsied infants. J Neuropathol Exp Neurol 47:217\u2013234","journal-title":"J Neuropathol Exp Neurol"},{"key":"599_CR20","doi-asserted-by":"crossref","unstructured":"Kinney HC, Volpe JJ (2009) Perinatal panencephalopathy in the premature infant: is it due to Hypoxia\u2013Ischemia?\u201d In: Haddad GG, Ping YS (eds) Perinatal Brain Hypoxia and Ischemia. Contemporary Clinical Neuroscience, The Humana Press, Totowa, pp 153\u2013185","DOI":"10.1007\/978-1-60327-579-8_8"},{"key":"599_CR21","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s00401-005-1077-6","volume":"110","author":"HC Kinney","year":"2005","unstructured":"Kinney HC, Panigrahy A, Newburger JW, Jonas RA, Sleeper LA (2005) Hypoxic\u2013ischemic brain injury in infants with congenital heart disease dying after cardiac surgery. Acta Neuropathol 110:563\u2013578","journal-title":"Acta Neuropathol"},{"key":"599_CR22","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1203\/PDR.0b013e31817da10a","volume":"64","author":"R Kumar","year":"2008","unstructured":"Kumar R, Macey PM, Woo MA, Alger JR, Harper RM (2008) Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome. Pediatr Res 64:275\u2013280","journal-title":"Pediatr Res"},{"key":"599_CR23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/0006-8993(79)90287-7","volume":"162","author":"P Levitt","year":"1979","unstructured":"Levitt P, Moore RY (1979) Development of the noradrenergic innervation of neocortex. Brain Res 162:243\u2013259","journal-title":"Brain Res"},{"key":"599_CR24","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1113\/jphysiol.2005.099325","volume":"570","author":"A Li","year":"2006","unstructured":"Li A, Nattie E (2006) Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability. J Physiol 570:385\u2013396","journal-title":"J Physiol"},{"key":"599_CR25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1113\/jphysiol.2006.114504","volume":"577","author":"A Li","year":"2006","unstructured":"Li A, Zhou S, Nattie E (2006) Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats. J Physiol 577:307\u2013318","journal-title":"J Physiol"},{"key":"599_CR26","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1212\/WNL.28.10.1013","volume":"28","author":"HM Liu","year":"1978","unstructured":"Liu HM, Loew JM, Hunt CE (1978) Congenital central hypoventilation syndrome: a pathologic study of the neuromuscular system. Neurology 28:1013\u20131019","journal-title":"Neurology"},{"key":"599_CR27","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1152\/japplphysiol.00969.2004","volume":"98","author":"PM Macey","year":"2005","unstructured":"Macey PM, Woo MA, Macey KE et al (2005) Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome. J Appl Physiol 98:958\u2013969","journal-title":"J Appl Physiol"},{"key":"599_CR28","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.resp.2007.01.019","volume":"157","author":"PF Martino","year":"2007","unstructured":"Martino PF, Davis S, Opansky C et al (2007) The cerebellar fastigial nucleus contributes to CO2\u2013H+ ventilatory sensitivity in awake goats. Respir Physiol Neurobiol 157:242\u2013251","journal-title":"Respir Physiol Neurobiol"},{"key":"599_CR29","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1136\/jmg.2003.015412","volume":"41","author":"I Matera","year":"2004","unstructured":"Matera I, Bachetti T, Puppo F et al (2004) PHOX2B mutations and polyalanine expansions correlate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset Central Hypoventilation syndrome. J Med Genet 41:373\u2013380","journal-title":"J Med Genet"},{"key":"599_CR30","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1152\/japplphysiol.01128.2001","volume":"92","author":"EE Nattie","year":"2002","unstructured":"Nattie EE, Li A (2002) CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness. J Appl Physiol 92:2119\u20132130","journal-title":"J Appl Physiol"},{"issue":"4","key":"599_CR31","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1152\/japplphysiol.00112.2008","volume":"106","author":"EE Nattie","year":"2008","unstructured":"Nattie EE, Li A (2008) Central chemoreception is a complex system function that involves multiple brainstem sites. J Appl Physiol 106(4):1464\u20131466","journal-title":"J Appl Physiol"},{"key":"599_CR32","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/978-0-387-73693-8_61","volume":"605","author":"NL Nichols","year":"2008","unstructured":"Nichols NL, Hartzler LK, Conrad SC, Dean JB, Putnam RW (2008) Intrinsic chemosensitivity of individual nucleus tractus solitarius (NTS) and locus coeruleus (LC) neurons from neonatal rats. Adv Exp Med Biol 605:348\u2013352","journal-title":"Adv Exp Med Biol"},{"key":"599_CR33","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.autneu.2005.12.009","volume":"124","author":"DS Paterson","year":"2006","unstructured":"Paterson DS, Thompson EG, Kinney HC (2006) Serotonergic and glutamatergic neurons at the ventral medullary surface of the human infant: observations relevant to central chemosensitivity in early human life. Auton Neurosci 124:112\u2013124","journal-title":"Auton Neurosci"},{"key":"599_CR34","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1006\/mcne.1999.0826","volume":"15","author":"A Pattyn","year":"2000","unstructured":"Pattyn A, Goridis C, Brunet JF (2000) Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Mol Cell Neurosci 15:235\u2013243","journal-title":"Mol Cell Neurosci"},{"key":"599_CR35","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1242\/dev.127.7.1349","volume":"127","author":"A Pattyn","year":"2000","unstructured":"Pattyn A, Hirsch M, Goridis C, Brunet JF (2000) Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development 127:1349\u20131358","journal-title":"Development"},{"key":"599_CR36","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/20700","volume":"399","author":"A Pattyn","year":"1999","unstructured":"Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF (1999) The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399:366\u2013370","journal-title":"Nature"},{"key":"599_CR37","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1176\/ajp.151.6.864","volume":"151","author":"DS Pine","year":"1994","unstructured":"Pine DS, Weese-Mayer DE, Silvestri JM, Davies M, Whitaker AH, Klein DF (1994) Anxiety and congenital central hypoventilation syndrome. Am J Psychiatry 151:864\u2013870","journal-title":"Am J Psychiatry"},{"key":"599_CR38","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s00439-003-1036-z","volume":"114","author":"A Sasaki","year":"2003","unstructured":"Sasaki A, Kanai M, Kijima K et al (2003) Molecular analysis of congenital central hypoventilation syndrome. Hum Genet 114:22\u201326","journal-title":"Hum Genet"},{"key":"599_CR39","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/nn1130","volume":"6","author":"CA Severson","year":"2003","unstructured":"Severson CA, Wang W, Pieribone VA, Dohle CI, Richerson GB (2003) Midbrain serotonergic neurons are central pH chemoreceptors. Nat Neurosci 6:1139\u20131140","journal-title":"Nat Neurosci"},{"key":"599_CR40","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1152\/jappl.2000.88.6.1996","volume":"88","author":"IC Solomon","year":"2000","unstructured":"Solomon IC, Edelman NH, O\u2019Neal MH 3rd (2000) CO(2)\/H(+) chemoreception in the cat pre-Botzinger complex in vivo. J Appl Physiol 88:1996\u20132007","journal-title":"J Appl Physiol"},{"key":"599_CR41","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0034-5687(01)00294-8","volume":"129","author":"CM Spengler","year":"2001","unstructured":"Spengler CM, Gozal D, Shea SA (2001) Chemoreceptive mechanisms elucidated by studies of congenital central hypoventilation syndrome. Respir Physiol 129:247\u2013255","journal-title":"Respir Physiol"},{"key":"599_CR42","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1203\/01.pdr.0000191814.73340.1d","volume":"59","author":"ES Todd","year":"2006","unstructured":"Todd ES, Weinberg SM, Berry-Kravis EM, Silvestri JM, Kenny AS, Rand CM, Zhou L, Maher BS, Marazita ML, Weese-Mayer DE (2006) Facial phenotype in children and young adults with PHOX2B-determined congenital central hypoventilation syndrome: quantitative pattern of dysmorphology. Pediatr Res 59:39\u201345","journal-title":"Pediatr Res"},{"key":"599_CR43","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/ajmg.a.20527","volume":"123A","author":"DE Weese-Mayer","year":"2003","unstructured":"Weese-Mayer DE, Berry-Kravis EM, Zhou L et al (2003) 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 A 123A:267\u2013278","journal-title":"Am J Med Genet A"},{"key":"599_CR44","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1164\/ajrccm\/137.2.393","volume":"137","author":"DE Weese-Mayer","year":"1988","unstructured":"Weese-Mayer DE, Brouillette RT, Naidich TP, McLone DG, Hunt CE (1988) Magnetic resonance imaging and computerized tomography in central hypoventilation. Am Rev Respir Dis 137:393\u2013398","journal-title":"Am Rev Respir Dis"},{"key":"599_CR45","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1203\/00006450-199203000-00020","volume":"31","author":"MS Woo","year":"1992","unstructured":"Woo MS, Woo MA, Gozal D, Jansen MT, Keens TG, Harper RM (1992) Heart rate variability in congenital central hypoventilation syndrome. Pediatr Res 31:291\u2013296","journal-title":"Pediatr Res"},{"key":"599_CR46","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1006\/geno.1999.5845","volume":"59","author":"M Yokoyama","year":"1999","unstructured":"Yokoyama M, Watanabe H, Nakamura M (1999) Genomic structure and functional characterization of NBPhox (PMX2B), a homeodomain protein specific to catecholaminergic cells that is involved in second messenger-mediated transcriptional activation. Genomics 59:40\u201350","journal-title":"Genomics"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-009-0599-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-009-0599-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-009-0599-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-009-0599-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T02:42:03Z","timestamp":1744166523000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-009-0599-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10,21]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,2]]}},"alternative-id":["599"],"URL":"https:\/\/doi.org\/10.1007\/s00401-009-0599-8","relation":{},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,21]]},"assertion":[{"value":"14 May 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2009","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2009","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2009","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}