CHARGE Syndrome Workup

  • Author: David H Tegay, DO, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 12, 2012
 

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, 8, 19]
  • 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.[26, 27]
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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.
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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.
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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.

Specialty Editor Board

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.

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.

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.

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 and Genetics, Director RSA, 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.

Additional Contributors

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.

References

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  28. 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].

 
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