FaCD Online Syndrome Fact Sheet

Last updated: 23 Jun 2011

Name: Congenital Central Hypoventilation Syndrome

Synonym: CCHS, Ondine Curse, incl. Ondine-Hirschsprung Disease

Mode of Inheritance: AR

OMIM number: 209880  


PHOX2B, mapped to 4p12

Tumor features

neuroblastoma, adrenal
neuroblastoma, extra-adrenal

Non-tumor features

Hirschsprung disease
hypoventilation, central


Germline PHOX2B mutations cause congenital central hypoventilation syndrome (CCHS)[1]. This syndrome is probably underdiagnosed because of the mild phenotypes in some of the families[2]. Germline PHOX2B alterations have also been reported in neuroblastoma cases with CCHS and/or Hirschsprung disease and also in a few non-syndromic familial as well as non-familial neuroblastoma patients[3-6]. In general, the chance of finding germline PHOX2B mutations in apparently sporadic neuroblastoma cases is small[7]. Ganglioneuroma has been reported in a PHOX2B family[3].


Neuroblastoma home page, Center for Medical Genetics page, University Hospital Gent, Belgium 23 1 08


[1] Bourdeaut F, Trochet D, Janoueix-Lerosey I, Ribeiro A, Deville A, Coz C, Michiels JF, Lyonnet S, Amiel J, Delattre O. Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Cancer letters 2005; 228(1-2):51-8.
[2] Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H; ATS Congenital Central Hypoventilation Syndrome Subcommittee. An official ATS clinical policy statement: Congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med. 2010 Mar 15;181(6):626-44.
[3] Trochet D, Bourdeaut F, Janoueix-Lerosey I, Deville A, de Pontual L, Schleiermacher G, Coze C, Philip N, Frébourg T, Munnich A, Lyonnet S, Delattre O, Amiel J. Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. American journal of human genetics 2004; 74(4):761-4.
[4] McConville C, Reid S, Baskcomb L, Douglas J, Rahman N. PHOX2B analysis in non-syndromic neuroblastoma cases shows novel mutations and genotype-phenotype associations. American journal of medical genetics. Part A 2006; 140(12):1297-301.
[5] Raabe EH, Laudenslager M, Winter C, Wasserman N, Cole K, LaQuaglia M, Maris DJ, Mosse YP, Maris JM. Prevalence and functional consequence of PHOX2B mutations in neuroblastoma. Oncogene 2008; 27(4):469-76.
[6] Grigg-Damberger M, Wells A. Central congenital hypoventilation syndrome: changing face of a less mysterious but more complex genetic disorder. Semin Respir Crit Care Med. 2009 Jun;30(3):262-74.
[7] Serra A, Häberle B, König IR, Kappler R, Suttorp M, Schackert HK, Roesner D, Fitze G. Rare occurrence of PHOX2b mutations in sporadic neuroblastomas. J Pediatr Hematol Oncol. 2008 Oct;30(10):728-32