European Journal of Pediatrics

, Volume 173, Issue 12, pp 1607–1609 | Cite as

An unusual cause of fetal hypomobility:congenital central hypoventilation syndrome associated with hirschsprung disease

  • Sybille De Montpellier
  • Yves Sznajer
  • Jeanne Amiel
  • Genevieve Francois
  • Marie-Cecile Nassogne
  • Christian Debauche
  • Isabelle Scheers
Case Report


Co-occurrence of congenital central hypoventilation syndrome and Hirschsprung disease is known as Haddad syndrome. Affected patients develop with variable expressivity a dysfunction of the autonomic nervous system. We report the natural history of a full-term newborn infant presenting multiple features of autonomic system dysfunction that were already noted antenatally. The presence of a nonpolyalanine repeat expansion mutation in the PHOX2B gene confirmed postnatally the diagnosis of Haddad syndrome. This case suggests that patients presenting with autonomic system dysfunction may already present signs of the disease during the fetal period. Furthermore, antenatal presentations may correlate with a more severe presentation of the disease. In conclusion, antenatal signs of dysautonomy should stimulate multidisciplinary prenatal approach to orientate proper postnatal intervention and facilitate treatment strategies.


Congenital central hypoventilation syndrome PHOX2B gene Haddad syndrome 


Ethical standards

The next of kin gave their written informed consent for the publication of their child’s case report.

Conflict of interests

The authors report that no conflicts of interest exist.


  1. 1.
    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 (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet 33:459–461PubMedCrossRefGoogle Scholar
  2. 2.
    Berry-Kravis EM, Zhou L, Rand CM, Weese-Mayer DE (2006) Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit Care Med 174:1139–1144PubMedCrossRefGoogle Scholar
  3. 3.
    Haddad GG, Mazza NM, Defendini R, Blanc WA, Driscoll JM, Epstein MA, Epstein RA, Mellins RB (1978) Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate. Medicine (Baltimore) 57:517–526CrossRefGoogle Scholar
  4. 4.
    Majumdar S, Wood P (2009) Congenital central hypoventilation syndrome (CCHS) with Hirschsprung disease (Haddad syndrome): an unusual cause of reduced baseline variability of the fetal heart rate. J Obstet Gynaecol 29:152–153PubMedCrossRefGoogle Scholar
  5. 5.
    Matera I, Bachetti T, Puppo F, Di Duca M, Morandi F, Casiraghi GM, Cilio MR, Hennekam R, Hofstra R, Schober JG, Ravazzolo R, Ottonello G, Ceccherini I (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 41:373–380PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Sagel SD, Cohen H, Townsend SF (1999) Neonatal Hirschsprung disease, dysautonomia, and central hypoventilation. Obstet Gynecol 93:834–836PubMedCrossRefGoogle Scholar
  7. 7.
    Trang H, Boureghda S, Denjoy I, Alia M, Kabaker M (2003) 24-hour BP in children with congenital central hypoventilation syndrome. Chest 124:1393–1399PubMedCrossRefGoogle Scholar
  8. 8.
    Trochet D, de Pontual L, Straus C, Gozal D, Trang H, Landrieu P, Munnich A, Lyonnet S, Gaultier C, Amiel J (2008) PHOX2B germline and somatic mutations in late-onset central hypoventilation syndrome. Am J Respir Crit Care Med 177:906–911PubMedCrossRefGoogle Scholar
  9. 9.
    Weese-Mayer DE, Silvestri JM, Menzies LJ, Morrow-Kenny AS, Hunt CE, Hauptman SA (1992) Congenital central hypoventilation syndrome: diagnosis, management, and long-term outcome in thirty-two children. J Pediatr 120:381–387PubMedCrossRefGoogle Scholar
  10. 10.
    Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H (2010) An official ATS clinical policy statement: Congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med 181:626–644PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sybille De Montpellier
    • 1
  • Yves Sznajer
    • 2
  • Jeanne Amiel
    • 3
  • Genevieve Francois
    • 1
  • Marie-Cecile Nassogne
    • 4
  • Christian Debauche
    • 5
  • Isabelle Scheers
    • 6
  1. 1.General Pediatrics and Sleep Disorders UnitCliniques Universitaires Saint-LucBrusselsBelgium
  2. 2.Center for Human GeneticsCliniques Universitaires Saint-LucBrusselsBelgium
  3. 3.Université Paris 5-Descartes, Faculté de Médecine, INSERM U-781, AP-HPHôpital Necker-Enfants MaladesParisFrance
  4. 4.Pediatric Neurology UnitCliniques Universitaires Saint-LucBrusselsBelgium
  5. 5.Neonatal Intensive Care UnitCliniques Universitaires Saint-LucBrusselsBelgium
  6. 6.Pediatric Gastroenterology, Hepatology and Nutrition UnitCliniques Universitaires Saint-LucBrusselsBelgium

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