Choanal Atresia, Esophageal Atresia, Facial Anomalies, and Dysautonomia

  • Francesco CozziEmail author
  • Denis A. Cozzi


This is a review of our main contributions to the literature regarding the physiological and clinical manifestations that infants with choanal atresia share with those with esophageal atresia. The common clinical picture is characterized by inspiratory and expiratory dyspnea, oropharyngeal dysphagia, gastroesophageal reflux and/or vomiting, bradycardia, sialorrhea, hyperhidrosis, hyperthermia, apparent life-threatening event, and sudden death. The common pathogenetic mechanism appears to be a maturational dysautonomia affecting multiple target sites of vagus nerve. A possible explanation of this association is a maldevelopment of the cephalic neural crest cells, which play an important role in the embryogenesis of face, esophagus, and autonomic nervous system. Support to this concept comes from the presence in infants with choanal atresia or esophageal atresia of similar minor facial anomalies, which are considered markers of a cephalic neural crest maldevelopment.


Choanal atresia Facial anomalies Dysautonomia, associated malformations 



We wish to thank Prof A Schiavetti and Dr S Frediani for their help and comments in the preparation of this chapter.


  1. 1.
    Richardson CW. Congenital atresia of the post nasal orifice. Lancet. 1914;II:439–44.CrossRefGoogle Scholar
  2. 2.
    New GB. Congenital obstruction of the larynx and pharynx. JAMA. 1923;81:363–6.CrossRefGoogle Scholar
  3. 3.
    Robin P. La chute de la base de la langue consideree comme une nouvelle cause de gene dans la respiration nasopharyngienne. Bull Acad Med. 1923;89:117.Google Scholar
  4. 4.
    Robin P. Traitement morpho-fonctionnel de la glossoptose et de la respiration par la bouche. Imprimerie de la Cour d’Appel, 1, rue Cassette, Paris; 1930.Google Scholar
  5. 5.
    Mercer RD. Laryngeal stridor with temporary cardiac and respiratory arrest. Am J Dis Child. 1945;70:336.CrossRefGoogle Scholar
  6. 6.
    Hough JV. The mechanism of asphyxia in bilateral choanal atresia: the technic of its surgical correction in the newborn. South Med J. 1955;48:588–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Mc Govern FH. Bilateral choanal atresia in the newborn – a new method of medical management. Laryngoscope. 1961;71:480–3.CrossRefGoogle Scholar
  8. 8.
    Sjovall K. The use of an oral airway in the treatment of respiratory distress of infants. Acta Paediatr. 1963;52:153–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Bolande RP. The neurocristopathies. Hum Pathol. 1974;5:409–29.CrossRefGoogle Scholar
  10. 10.
    Cozzi F. Glossoptosis as cause of apnoeic spells in infants with choanal atresia. Lancet. 1977;2(8042):830–1.CrossRefPubMedGoogle Scholar
  11. 11.
    Le Douarin N. The neural crest. Cambridge, UK: Cambridge University Press; 1982.Google Scholar
  12. 12.
    Siebert JR. Facial and cardiac anomlaies. Science. 1983;221:908.CrossRefPubMedGoogle Scholar
  13. 13.
    Bower RJ, Akins JC. Ondine’s course and neurocristopathy. Clin Pediatr. 1980;19:665–8.CrossRefGoogle Scholar
  14. 14.
    Cozzi F, Pierro A. Glossoptosis-apnea syndrome in infancy. Pediatrics. 1985;75:836–43.PubMedGoogle Scholar
  15. 15.
    Fearon B, Shortreed R. Tracheobronchial compression by congenital cardiovascular anomalies in children. Syndrome of apnea. Ann Otol Rhinol Laryngol. 1963;72:949–69.CrossRefPubMedGoogle Scholar
  16. 16.
    Gross RE, Neuhauser EB. Compression of the trachea by an anomalous innominate artery; an operation for its relief. Am J Dis Child. 1948;75:570–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Harrison VC, Heese Hde V, Klein M. The significance of grunting in hyaline membrane disease. Pediatrics. 1968;41:549–59.PubMedGoogle Scholar
  18. 18.
    Kinney HC, Thach BT. The sudden infant death syndrome. N Engl J Med. 2009;361(8):795–805.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lindroth M, Johnson B, Ahlström H, et al. Pulmonary mechanics in early infancy. Subclinical grunting in low-birth-weight infants. Pediatr Res. 1981;15:979–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Medovy H, Beckman IH. Asphyxial attacks in the newborn infant due to congenital occlusion of the posterior nares; report of five cases. Pediatrics. 1951;8:678–83.PubMedGoogle Scholar
  21. 21.
    Swift PG, Emery JL. Clinical observations on response to nasal occlusion in infancy. Arch Dis Child. 1973;48:947–51.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Whitehouse WM, Holt JF. Paradoxical expiratory ballooning of the hypopharynx in siblings with bilateral choanal atresia. Radiology. 1952;59:216–20.CrossRefPubMedGoogle Scholar
  23. 23.
    Lowe AA, Gurza SC, Sessle BJ. Regulation of genioglossus and masseter muscle activity in man. Arch Oral Biol. 1977;22:579–84.CrossRefPubMedGoogle Scholar
  24. 24.
    Remmers JE, deGroot WJ, Sauerland EK, et al. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol. 1978;44:931–8.PubMedGoogle Scholar
  25. 25.
    Cozzi F, Albani R, Cardi E. A common pathophysiology for sudden cot death and sleep apnoea. “The vacuum-glossoptosis syndrome”. Med Hypotheses. 1979;5:329–38.CrossRefPubMedGoogle Scholar
  26. 26.
    Tonkin SL, Partridge J, Beach D, et al. The pharyngeal effect of partial nasal obstruction. Pediatrics. 1979;63:261–71.PubMedGoogle Scholar
  27. 27.
    Mathew OP, Abu-Osba YK, Thach BT. Genioglossus muscle responses to upper airway pressure changes: afferent pathways. J Appl Physiol. 1982;52:445–50.PubMedGoogle Scholar
  28. 28.
    Couly G, Lagrue A, Griscelli C. Di George syndrome, exemplary rhomboencephalic neurocristopathy. Rev Stomatol Chir Maxillofac. 1983;84:103–8.PubMedGoogle Scholar
  29. 29.
    van Lunteren E, Van de Graaff WB, Parker DM, et al. Nasal and laryngeal reflex responses to negative upper airway pressure. J Appl Physiol. 1984;56:746–52.CrossRefPubMedGoogle Scholar
  30. 30.
    Reed WR, Roberts JL, Thach BT. Factors influencing regional patency and configuration of the human infant upper airway. J Appl Physiol. 1985;58:635–44.PubMedGoogle Scholar
  31. 31.
    Siebert JR, Graham Jr JM, MacDonald C. Pathologic features of the CHARGE association: support for involvement of the neural crest. Teratology. 1985;31:331–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Leppig KA, Werler MM, Cann CI, et al. Predictive value of minor anomalies. I. Association with major malformations. J Pediatr. 1987;110:531–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Narcy C, Foucaud P, Cargill G, et al. The association of megaesophagus, Binder’s syndrome and dysautonomia: a new neurocristopathy. Arch Fr Pediatr. 1987;44:119–21.PubMedGoogle Scholar
  34. 34.
    Couly G, Cheron G, de Blic J. The Pierre-Robin syndrome. Classification and new therapeutic approach. Arch Fr Pediatr. 1988;45:553–9.PubMedGoogle Scholar
  35. 35.
    Cozzi F, Steiner M, Rosati D, et al. Clinical manifestations of choanal atresia in infancy. J Pediatr Surg. 1988;23:203–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Southall DP, Samuels MP, Talbert DG. Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death. Arch Dis Child. 1990;65:953–61.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Cozzi F, Myers NA, Madonna L, et al. Esophageal atresia, choanal atresia, and dysautonomia. J Pediatr Surg. 1991;26:548–52.CrossRefPubMedGoogle Scholar
  38. 38.
    Francois M, Elmaleh M, Garel C, et al. Dimensions du pharynx en fonction de la position, chez la nouveau-nè et le nourrisson. Arch Fr Pediatr. 1992;49:23–6.PubMedGoogle Scholar
  39. 39.
    Cozzi F, Myers NA, Piacenti S, et al. Maturational dysautonomia and facial anomalies associated with esophageal atresia: support for neural crest involvement. J Pediatr Surg. 1993;28:798–801.CrossRefPubMedGoogle Scholar
  40. 40.
    Mitchell EA, Taylor BJ, Ford RP, et al. Dummies and the sudden infant death syndrome. Arch Dis Child. 1993;68:501–4.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Cozzi DA, Bonanni M, Cozzi F. Recurrent apparent life-threatening event relieved by glossopexy. J Pediatr Surg. 1996;31:1715–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Cozzi F, Bonanni M, Cozzi DA. Assessment of pulmonary mechanics and breathing patterns during posturally induced glossoptosis in infants. Arch Dis Child. 1996;74:512–6.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Rees K, Wright A, Keeling JW, et al. Facial structure in the sudden infant death syndrome: case-control study. BMJ. 1998;317:179–80.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Cozzi DA, Capocaccia P, Roggini M, et al. Respiratory status of infants with esophageal atresia. Pediatr Surg Int. 2001;17:92–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Morini F, Cozzi DA, Ilari M, et al. Pattern of cardiovascular anomalies associated with esophageal atresia: support for a caudal pharyngeal arch neurocristopathy. Pediatr Res. 2001;50:565–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Cozzi F, Morini F, Casati A, et al. Glossopexy as an alternative to aortopexy in infants with repaired esophageal atresia and upper airway obstruction. J Pediatr Surg. 2002;37:202–6.CrossRefPubMedGoogle Scholar
  47. 47.
    Cozzi F, Morini F, Tozzi C, et al. Effect of pacifier use on oral breathing in healthy infants. Pediatr Pulmonol. 2002;33:368–73.CrossRefPubMedGoogle Scholar
  48. 48.
    American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005;116:1245–55.CrossRefGoogle Scholar
  49. 49.
    Hauck FR, Omojokun OO, Siadaty MS. Do pacifiers reduce the risk of sudden infant death syndrome? A meta-analysis. Pediatrics. 2005;116:e716–23.CrossRefPubMedGoogle Scholar
  50. 50.
    Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome. Lancet. 2007;370(9598):1578–87.CrossRefPubMedGoogle Scholar
  51. 51.
    Pasquale-Styles MA, Tackitt PL, Schmidt CJ. Infant death scene investigation and the assessment of potential risk factors for asphyxia: a review of 209 sudden unexpected infant deaths. J Forensic Sci. 2007;52:924–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Audero E, Coppi E, Mlinar B, et al. Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition. Science. 2008;321(5885):130–3.CrossRefPubMedGoogle Scholar
  53. 53.
    Cozzi F, Totonelli G, Frediani S, et al. The effect of glossopexy on weight velocity in infants with Pierre Robin syndrome. J Pediatr Surg. 2008;43:296–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Ramsden JD, Campisi P, Forte V. Choanal atresia and choanal stenosis. Otolaryngol Clin North Am. 2009;42:339–52.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Pediatric Surgery UnitUniversity of Rome “La Sapienza”, Azienda Policlinico Umberto IRomeItaly

Personalised recommendations