Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

CHARGE Syndrome (CHD7, SEMA3E)

  • Melissa L. CrenshawEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_167-1



CHARGE syndrome is a well-described genetic condition affecting multiple body systems and more recently noted to be associated with immunodeficiency. This is recognized as the co-occurrence of anomalies including the eyes (coloboma), heart (congenital heart defects), choanal atresia, retardation of somatic and mental development, genitourinary anomalies, and ear anomalies (Pagon et al. 1981).

The majority of individuals with CHARGE syndrome are de novo. However, rarely familiar cases are described with autosomal dominant inheritance. Over 90% of individuals with typical CHARGE have a heterozygous pathogenic change in the gene CHD7 (Vissers et al. 2004), which encodes the chromodomain helicase DNA-binding protein 7. SEMA3E has also been reported as a causative gene in at least two affected persons (Lalani et al. 2004). This produces the protein semaphorin 3E. This is an autosomal dominant condition with most cases being sporadic.

CHARGE Syndrome

This is a preview of subscription content, log in to check access.


  1. Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, Chang CP, Zhao Y, Swigut T, Wysocka J. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature. 2010;463:958–62.CrossRefGoogle Scholar
  2. Chopra C, Baretto R, Duddridge M, Browning MJ. T-cell immunodeficiency in CHARGE syndrome. Acta Paediatr. 2009;98(2):408–10.CrossRefGoogle Scholar
  3. Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, Montgomery T, Goodship JA, Burt AD, Flood TJ, Abinum M, Cant AJ, Johnson D. Mutations in CHD7 in patients with CHARGE syndrome cause T–B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome. Clin Exp Immunol. 2008;153:75–80.CrossRefGoogle Scholar
  4. Hsu P, Ma A, Barnes EH, Stat M, Wilson M, Hoefsloot LH, Rinne T, Munns C, Williams G, Wong M, Mehr S. The immune phenotype of patients with CHARGE syndrome. J Allergy Clin Immunol Pract. 2016;4(1):96–103.CrossRefGoogle Scholar
  5. Janssen N, Bergman JE, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RM, van Ravenswaaij-Arts CM, Hoefsloot LH. Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat. 2012;33(8):1149–60.CrossRefGoogle Scholar
  6. Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L, van Hagen JM, Donnai D, de Ravel TJ, Veltman JA, van Kessel AG, De Vries BB, Brunner HG, Hoefsloot LH, van Ravenswaaij CM. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006;43(4):306–14.CrossRefGoogle Scholar
  7. Lalani Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW. SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet. 2004; 41(7):e94.CrossRefGoogle Scholar
  8. Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet. 2006;78(2):303–14.CrossRefGoogle Scholar
  9. Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109:4539–47.CrossRefGoogle Scholar
  10. Pagon AP, Graham JM, Siu-Li Y. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. 1981;99(2):223–7.CrossRefGoogle Scholar
  11. Polleux F, Morrow T, Ghosh A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature. 2000;404(6778):567–73.CrossRefGoogle Scholar
  12. Sanka M, Tangsinmankong N, Loscalzo M, Sleasman JW, Dorsey M. Complete DiGeorge syndrome associated with CHD7 mutation. J Allergy Clin Immunol. 2007;120(4):952–4.CrossRefGoogle Scholar
  13. Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F, Zammataro L, Primo L, Tamagnone L, Logan M, Tessier-Lavigne M, Taniguchi M, Puschel AW, Bussolino F. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature. 2003;424:391–7.CrossRefGoogle Scholar
  14. Verloes. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. 2005;133A(3):303–8.CrossRefGoogle Scholar
  15. Vissers LE, Ravenswaaij RA, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36(9):955–7.CrossRefGoogle Scholar
  16. Wong MT, Lambeck AJ, van der Burg M, la Bastidevan Gemert S, Hogendorf LA, van Ravenswaaij-Arts CM, Schölvinck EH. Immune dysfunction in children with CHARGE syndrome: a cross-sectional study. PLoS One. 2015a;10(11):e0142350.CrossRefGoogle Scholar
  17. Wong MT, Schölvinck EH, Lambeck AJ, van Ravenswaaij-Arts CM. CHARGE syndrome: a review of the immunological aspects. Eur J Hum Genet. 2015b;23:1451–9.CrossRefGoogle Scholar
  18. Writzl K, Cale CM, Pierce CM, Wilson LC, Hennekan RC. Immunological abnormalities in CHARGE syndrome. Eur J Med Genet. 2007;50(5):338–45.CrossRefGoogle Scholar
  19. Zentner GE, Hurd EA, Schnetz MP, Handoko L, Wang C, Wang Z, Wei C, Tesar PJ, Hatzoglou M, Martin DM, Scacheri PC. CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis. Hum Mol Genet. 2010;19(18):3491–501.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of GeneticsJohns Hopkins All Children’s HospitalSt. PetersburgUSA

Section editors and affiliations

  • Jolan Walter
    • 1
  1. 1.USF HealthTampaUSA