eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

CHARGE Syndrome: Differential Diagnoses & Workup

Author: David H Tegay, DO, FACMG, Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center
Coauthor(s): Jamie C Yedowitz, New York College of Osteopathic Medicine of the New York Institute of Technology
Contributor Information and Disclosures

Updated: Nov 13, 2009

Differential Diagnoses

DiGeorge Syndrome
Smith-Lemli-Opitz Syndrome
Velocardiofacial Syndrome

Other Problems to Be Considered

Cat-eye syndrome
Holoprosencephaly spectrum disorders
Isolated coloboma
Isolated choanal atresia
Isolated congenital heart defects
VATER/VACTERL association

Workup

Laboratory Studies

  • CHD7 mutation analysis is diagnostic in 58-71% of individuals referred with presumptive CHARGE syndrome. Some studies suggest this may be as much as 90% in those meeting strict clinical criteria for definite CHARGE syndrome. Genotype-phenotype understanding is increasing.1,6,17
  • High-resolution karyotype (chromosome analysis).
  • Fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (aCGH) can be used to detect submicroscopic copy number variations involving CHD7 and at other loci in individuals in whom CHD7 sequencing is uninformative.1
  • BUN, creatinine, electrolytes: Evaluate and monitor renal function and exclude hypocalcemia (DiGeorge syndrome).
  • Luteinizing hormone-releasing hormone (LHRH) and human chorionic gonadotropin (HCG): Perform these tests to evaluate the pituitary gonadal axis in cases of hypogenitalism.
  • Growth hormone levels: Obtain growth hormone levels to exclude growth hormone deficiency contributing to growth retardation.
  • CBC count and immunology studies: Immunodeficiency has been reported and is primarily T-cell based but may also be humoral, even appearing like Omenn syndrome.23,24

Imaging Studies

  • Chest radiography: Perform chest radiography to exclude cardiopulmonary pathology and to document normal lung volume and cardiac shape and size in persons with respiratory distress, especially in the newborn period.
  • Cranial ultrasonography: Perform this study in the immediate neonatal period to exclude major malformations of the brain.
  • Head CT scanning and/or MRI, including the temporal bones: Perform CT scanning and/or MRI to exclude cerebral malformation and cerebral atrophy and to exclude defective formation of the ossicles of the middle ear. MRI of the brain may reveal cerebral atrophy, midline brain defects (eg, agenesis of corpus callosum), and forebrain anomalies, particularly arrhinencephaly. CT scanning of the temporal bone reveals partial or complete semicircular canal hypoplasia. Ideally, evaluate the internal ear in later infancy or early childhood, when the ear is more fully formed.
  • Barium swallow: Perform this study to diagnose swallow dysfunction and/or esophageal dysmotility and tracheal aspiration.
  • Abdominal ultrasonography: Perform abdominal ultrasonography to exclude renal anomalies.
  • Skeletal survey: Survey the skeleton to exclude skeletal anomalies.
  • Echocardiography: Perform echocardiography to identify or exclude congenital cardiac defects.

Other Tests

  • Electroencephalogram: Perform EEG to diagnose seizures.
  • Immune system evaluation: Evaluate the immune system to exclude cellular immunodeficiency or lymphopenia and lymphocyte function defect (DiGeorge syndrome overlap).
  • ECG: Perform to identify and/or exclude congenital cardiac defects.
  • Serial audiometry and auditory brainstem evoked responses
    • Document the type and severity of conductive and sensorineural hearing loss.
    • A characteristic wedge-shaped response is reported.
  • Visual evoked response and electroretinogram
    • Identify and document the severity of visual loss.
    • Visual evoked response (VER) and electroretinogram (ERG) are abnormal but do not correlate with the extent or the localization of the coloboma.
    • Due to cognitive defects, administering tests of visual acuity is difficult; hence, more sophisticated tests (eg, VER, ERG) that do not depend on patient behavior responses are appropriate.

More on CHARGE Syndrome

Overview: CHARGE Syndrome
Differential Diagnoses & Workup: CHARGE Syndrome
Treatment & Medication: CHARGE Syndrome
Follow-up: CHARGE Syndrome
Multimedia: CHARGE Syndrome
References
[ CLOSE WINDOW ]

References

  1. Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. Sep 2004;36(9):955-7. [Medline].

  2. [Guideline] Pagon RA, Graham JM Jr, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. Aug 1981;99(2):223-7. [Medline].

  3. [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). Mar 1998;37(3):159-73. [Medline].

  4. [Guideline] Verloes A. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. Mar 15 2005;133A(3):306-8. [Medline].

  5. Jones KL. CHARGE association. In: Smith's Recognizable Patterns of Human Malformation. 5th ed. WB Saunders Co; 1997:668-70.

  6. Aramaki M, Udaka T, Kosaki R, Makita Y, Okamoto N, Yoshihashi H. Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr. Mar 2006;148(3):410-4. [Medline].

  7. 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. Nov 1 1991;41(2):246-50. [Medline].

  8. 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. Jul 17 1995;57(4):610-4. [Medline].

  9. 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. Dec 2000;37(12):E47. [Medline].

  10. Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW. SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet. Jul 2004;41(7):e94. [Medline].

  11. Williams MS. Speculations on the pathogenesis of CHARGE syndrome. Am J Med Genet A. Mar 15 2005;133A(3):318-25. [Medline].

  12. 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. Mar 2006;43(3):211-317. [Medline].

  13. 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. Mar 15 2005;133A(3):309-17. [Medline].

  14. Kallen K, Robert E, Mastroiacovo P, et al. CHARGE Association in newborns: a registry-based study. Teratology. Dec 1999;60(6):334-43. [Medline].

  15. 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. Feb 1990;65(2):217-23. [Medline].

  16. Tellier AL, Cormier-Daire V, Abadie V, et al. CHARGE syndrome: report of 47 cases and review. Am J Med Genet. Apr 13 1998;76(5):402-9. [Medline].

  17. Jongmans MC, Admiraal RJ, van der Donk KP, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. Apr 2006;43(4):306-14. [Medline].

  18. Davenport SL, Hefner MA, Mitchell JA. The spectrum of clinical features in CHARGE syndrome. Clin Genet. Apr 1986;29(4):298-310. [Medline].

  19. 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. Feb 2006;78(2):303-14. [Medline].

  20. 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. Sep-Oct 2008;51(5):417-25. [Medline].

  21. 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. Apr 1 2007;143(7):721-6. [Medline].

  22. 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. Jul 2008;45(7):432-7. [Medline].

  23. Writzl K, Cale CM, Pierce CM, Wilson LC, Hennekam RC. Immunological abnormalities in CHARGE syndrome. Eur J Med Genet. Sep-Oct 2007;50(5):338-45. [Medline].

  24. 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. Jul 2008;153(1):75-80. [Medline].

  25. Arndt S, Laszig R, Beck R, et al. Spectrum of Hearing Disorders and Their Management in Children With CHARGE Syndrome. Otol Neurotol. Oct 16 2009;[Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

CHARGE syndrome, coloboma, heart anomalies, choanal atresia, retardation of growth and development, genital and ear anomalies, CHARGE Association, CHD-7 spectrum disorder, treatment, diagnosis, symptoms

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

David H Tegay, DO, FACMG, Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center
David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology
Disclosure: Nothing to disclose.

Coauthor(s)

Jamie C Yedowitz, New York College of Osteopathic Medicine of the New York Institute of Technology
Disclosure: Nothing to disclose.

Medical Editor

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 American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.