Further Outpatient Care

See the list below:

Long-term coordination of care is necessary in patients with CHARGE syndrome.
Ensure follow-up care and recognition and prevention of complications.

Transfer

See the list below:

A tertiary hospital with appropriate pediatric subspecialists should coordinate and undertake care.

Complications

See the list below:

Eye - Corneal ulceration, retinal detachment

Patient Education

See the list below:

Families of patients with CHARGE syndrome require education regarding the disease manifestations and potential complications.
Discuss the genetic basis of the disorder and include the recurrence risks (1-2% for unaffected parents, as much as 50% for affected individuals).
Genetic counseling should be made available for individuals at increased risk for affected offspring to explain options in future pregnancies, including prenatal and preimplantation genetic diagnosis.
Familial cases do occur; although autosomal dominant heritance with variable expression is rare, it does occur.

Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004 Sep. 36(9):955-7. [QxMD MEDLINE Link].
Zentner GE, Layman WS, Martin DM, Scacheri PC. Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome. Am J Med Genet A. 2010 Mar. 152A(3):674-86. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Pagon RA, Graham JM Jr, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. 1981 Aug. 99(2):223-7. [QxMD MEDLINE Link].
Pampal A. CHARGE: an association or a syndrome?. Int J Pediatr Otorhinolaryngol. 2010 Jul. 74(7):719-22. [QxMD MEDLINE Link].
[Guideline] Blake KD, Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS. CHARGE association: an update and review for the primary pediatrician. Clin Pediatr (Phila). 1998 Mar. 37(3):159-73. [QxMD MEDLINE Link].
[Guideline] Verloes A. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. 2005 Mar 15. 133A(3):306-8. [QxMD MEDLINE Link]. [Full Text].
[Guideline] de Geus CM, Free RH, Verbist BM, et al. Guidelines in CHARGE syndrome and the missing link: Cranial imaging. Am J Med Genet C Semin Med Genet. 2017 Dec. 175 (4):450-64. [QxMD MEDLINE Link]. [Full Text].
Jones KL. CHARGE SYNDROME. Smith's Recognizable Patterns of Human Malformation. 7th ed. WB Saunders Co; 2013. 330-331.
Bergman JE, Janssen N, Hoefsloot LH, Jongmans MC, Hofstra RM, van Ravenswaaij-Arts CM. CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype. J Med Genet. 2011 May. 48(5):334-42. [QxMD MEDLINE Link].
Hefner MA, Fassi E. Genetic counseling in CHARGE syndrome: Diagnostic evaluation through follow up. Am J Med Genet C Semin Med Genet. 2017 Dec. 175 (4):407-16. [QxMD MEDLINE Link]. [Full Text].
Hale, CL, Niederriter, AN, Green, GE, et al. Atypical Phenotypes Associated with Pathogenic CHD7 Varaints and a Proposal for Broadening CHARGE Syndrome Clinical Diagnostic Criteria. American Journal of Medical Genetics. 170A:344-354. [QxMD MEDLINE Link]. [Full Text].
Aramaki M, Udaka T, Kosaki R, Makita Y, Okamoto N, Yoshihashi H. Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr. 2006 Mar. 148(3):410-4. [QxMD MEDLINE Link].
Clementi M, Tenconi R, Turolla L, Silvan C, Bortotto L, Artifoni L. Apparent CHARGE association and chromosome anomaly: chance or contiguous gene syndrome. Am J Med Genet. 1991 Nov 1. 41(2):246-50. [QxMD MEDLINE Link].
North KN, Wu BL, Cao BN, Whiteman DA, Korf BR. CHARGE association in a child with de novo inverted duplication (14)(q22-->q24.3). Am J Med Genet. 1995 Jul 17. 57(4):610-4. [QxMD MEDLINE Link].
Lev D, Nakar O, Bar-Am I, Zudik A, Watemberg N, Finkelstien S. CHARGE association in a child with de Novo chromosomal aberration 46, X,der(X)t(X;2)(p22.1;q33) detected by spectral karyotyping. J Med Genet. 2000 Dec. 37(12):E47. [QxMD MEDLINE Link].
Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW. SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet. 2004 Jul. 41(7):e94. [QxMD MEDLINE Link].
Ufartes R, Schwenty-Lara J, Freese L, et al. Sema3a plays a role in the pathogenesis of CHARGE syndrome. Hum Mol Genet. 2018 Apr 15. 27 (8):1343-52. [QxMD MEDLINE Link].
Moccia A, Srivastava A, Skidmore JM, et al. Genetic analysis of CHARGE syndrome identifies overlapping molecular biology. Genet Med. 2018 Jan 4. [QxMD MEDLINE Link]. [Full Text].
Williams MS. Speculations on the pathogenesis of CHARGE syndrome. Am J Med Genet A. 2005 Mar 15. 133A(3):318-25. [QxMD MEDLINE Link].
Sanlaville D, Etchevers HC, Gonzales M, et al. Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet. 2006 Mar. 43(3):211-317. [QxMD MEDLINE Link]. [Full Text].
Issekutz KA, Graham JM Jr, Prasad C, Smith IM, Blake KD. An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study. Am J Med Genet A. 2005 Mar 15. 133A(3):309-17. [QxMD MEDLINE Link].
Kallen K, Robert E, Mastroiacovo P, et al. CHARGE Association in newborns: a registry-based study. Teratology. 1999 Dec. 60(6):334-43. [QxMD MEDLINE Link].
Blake KD, Russell-Eggitt IM, Morgan DW, Ratcliffe JM, Wyse RK. Who's in CHARGE? Multidisciplinary management of patients with CHARGE association. Arch Dis Child. 1990 Feb. 65(2):217-23. [QxMD MEDLINE Link].
Tellier AL, Cormier-Daire V, Abadie V, et al. CHARGE syndrome: report of 47 cases and review. Am J Med Genet. 1998 Apr 13. 76(5):402-9. [QxMD MEDLINE Link].
Jongmans MC, Admiraal RJ, van der Donk KP, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006 Apr. 43(4):306-14. [QxMD MEDLINE Link].
Davenport SL, Hefner MA, Mitchell JA. The spectrum of clinical features in CHARGE syndrome. Clin Genet. 1986 Apr. 29(4):298-310. [QxMD MEDLINE Link].
Kong F, Martin DM. Atopic disorders in CHARGE syndrome: A retrospective study and literature review. Eur J Med Genet. 2018 Apr. 61 (4):225-9. [QxMD MEDLINE Link].
Legendre M, Abadie V, Attie-Bitach T, et al. Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome. Am J Med Genet C Semin Med Genet. 2017 Dec. 175 (4):417-30. [QxMD MEDLINE Link].
Nishina S, Kosaki R, Yagihashi T, Azuma N, Okamoto N, Hatsukawa Y, et al. Ophthalmic features of CHARGE syndrome with CHD7 mutations. Am J Med Genet A. 2012 Mar. 158A(3):514-8. [QxMD MEDLINE Link].
da Costa Monsanto R, Knoll RM, de Oliveira Penido N, et al. Otopathologic Abnormalities in CHARGE Syndrome. Otolaryngol Head Neck Surg. 2022 Feb. 166 (2):363-72. [QxMD MEDLINE Link].
Sohn YB, Ko JM, Shin CH, Yang SW, Chae JH, Lee KA. Cerebellar vermis hypoplasia in CHARGE syndrome: clinical and molecular characterization of 18 unrelated Korean patients. J Hum Genet. 2016 Mar. 61 (3):235-9. [QxMD MEDLINE Link].
Yu T, Meiners LC, Danielsen K, et al. Deregulated FGF and homeotic gene expression underlies cerebellar vermis hypoplasia in CHARGE syndrome. Elife. 2013 Dec 24. 2:e01305. [QxMD MEDLINE Link]. [Full Text].
Isaac KV, Ganske IM, Rottgers SA, Lim SY, Mulliken JB. Cleft Lip and Palate in CHARGE Syndrome: Phenotypic Features That Influence Management. Cleft Palate Craniofac J. 2018 Mar. 55 (3):342-7. [QxMD MEDLINE Link].
Van de Laar I, Dooijes D, Hoefsloot L, Simon M, Hoogeboom J, Devriendt K. Limb anomalies in patients with CHARGE syndrome: an expansion of the phenotype. Am J Med Genet A. 2007 Nov 15. 143A (22):2712-5. [QxMD MEDLINE Link].
Brock KE, Mathiason MA, Rooney BL, Williams MS. Quantitative analysis of limb anomalies in CHARGE syndrome: correlation with diagnosis and characteristic CHARGE anomalies. Am J Med Genet A. 2003 Nov 15. 123A (1):111-21. [QxMD MEDLINE Link].
Lalani SR, Safiullah AM, Fernbach SD, et al. Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation. Am J Hum Genet. 2006 Feb. 78(2):303-14. [QxMD MEDLINE Link].
Bergman JE, de Wijs I, Jongmans MC, Admiraal RJ, Hoefsloot LH, van Ravenswaaij-Arts CM. Exon copy number alterations of the CHD7 gene are not a major cause of CHARGE and CHARGE-like syndrome. Eur J Med Genet. 2008 Sep-Oct. 51(5):417-25. [QxMD MEDLINE Link].
Udaka T, Okamoto N, Aramaki M, Torii C, Kosaki R, Hosokai N. An Alu retrotransposition-mediated deletion of CHD7 in a patient with CHARGE syndrome. Am J Med Genet A. 2007 Apr 1. 143(7):721-6. [QxMD MEDLINE Link].
van Ravenswaaij-Arts C, Martin DM. New insights and advances in CHARGE syndrome: Diagnosis, etiologies, treatments, and research discoveries. Am J Med Genet C Semin Med Genet. 2017 Dec. 175 (4):397-406. [QxMD MEDLINE Link]. [Full Text].
Monfort S, Roselló M, Orellana C, Oltra S, Blesa D, Kok K, et al. Detection of known and novel genomic rearrangements by array based comparative genomic hybridisation: deletion of ZNF533 and duplication of CHARGE syndrome genes. J Med Genet. 2008 Jul. 45(7):432-7. [QxMD MEDLINE Link].
Writzl K, Cale CM, Pierce CM, Wilson LC, Hennekam RC. Immunological abnormalities in CHARGE syndrome. Eur J Med Genet. 2007 Sep-Oct. 50(5):338-45. [QxMD MEDLINE Link].
Gennery AR, Slatter MA, Rice J, Hoefsloot LH, Barge D, McLean-Tooke A, et al. 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 Jul. 153(1):75-80. [QxMD MEDLINE Link].
Mahdi ES, Whitehead MT. Clival Malformations in CHARGE Syndrome. AJNR Am J Neuroradiol. 2018 Jun. 39 (6):1153-6. [QxMD MEDLINE Link].
Arndt S, Laszig R, Beck R, et al. Spectrum of Hearing Disorders and Their Management in Children With CHARGE Syndrome. Otol Neurotol. 2009 Oct 16. [QxMD MEDLINE Link].
Vincenti V, Di Lella F, Falcioni M, Negri M, Zanetti D. Cochlear implantation in children with CHARGE syndrome: a report of eight cases. Eur Arch Otorhinolaryngol. 2018 Aug. 275 (8):1987-93. [QxMD MEDLINE Link].

Media Gallery

Typical ear malformation

of 1

Author

Megan Ehlinger Boothe, MD Clinical Assistant Professor, Department of Pediatrics, Division of Genetics and Metabolism, UFHealth, University of Florida College of Medicine

Megan Ehlinger Boothe, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Nathaniel H Robin, MD Professor, Departments of Genetics and Pediatrics, University of Alabama at Birmingham, Marnix E Heersink School of Medicine; Medical Director of Genetics, UAB Medicine

Nathaniel H Robin, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate-Craniofacial Association, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

David H Tegay, DO, FACMG Associate Professor and Chair, Department of Medicine, NYIT College of Osteopathic Medicine; Director, Genetics Division, Department of Pediatrics, Nassau University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American College of Osteopathic Internists, American Osteopathic Association, Federation of American Societies for Experimental Biology, American Society of Human Genetics

Disclosure: Nothing to disclose.

Jamie C Yedowitz New York College of Osteopathic Medicine of the New York Institute of Technology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Venkataraman Krishnan, MBBS, DCH, MRCP, FAAP, MD to the development and writing of this article.