eMedicine Specialties > Dermatology > Pediatric Diseases

DiGeorge Syndrome

Author: Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Nov 1, 2007

Introduction

Background

DiGeorge anomaly is one of a group of disorders that share a chromosome deletion resulting in monosomy 22q11. These disorders include cardiac defect, abnormal face, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH-22) syndrome1,2 ; conotruncal anomaly face syndrome; and DiGeorge anomaly syndrome.

Pathophysiology

This condition is a heterogeneous genodermatosis with deletions of chromosome band 22q11, which result in monosomy 22q11. The clinical syndrome results from a congenital developmental field defect with malformation of the third and fourth pharyngeal pouches. Patients have a variable T-cell deficiency resulting from faulty embryologic development of the thymus and parathyroid glands. A combined T- and B-cell deficiency may result from lack of T-helper cell function. Other features include cardiac abnormalities; parathyroid deficiency; hypocalcemia; characteristic facies; and recurrent infections, especially oral candidiasis.

Although band 22q11.2 deletion is the most common etiology of DiGeorge anomaly, other chromosomal anomalies (namely TBX1 gene mutations3 ), teratogens, and maternal diabetes have also been implicated. The DiGeorge critical region 6 gene is present in 2 highly homologous copies (DGCR64 and DCGR6L) on band 22q11, and deletions of this gene results in velocardiofacial syndrome/DiGeorge syndrome.

Frequency

United States

DiGeorge syndrome is rare. The 22q11 deletion is estimated to occur in approximately 1 in 4000 live births.

International

DiGeorge syndrome is rare.

Mortality/Morbidity

  • Severe cases manifest with severe combined immune deficiency (SCID).
  • Death is typically caused by infection during early infancy.

Race

No racial predilection is reported.

Sex

No sex predilection is recognized.

Age

DiGeorge syndrome is congenital.

Clinical

History

  • Depending on the degree of T-cell dysfunction, infection is the primary problem and leads to early death.
  • Endocrinologic problems associated with parathyroid deficiency must be addressed. These include the following:
    • Hypocalcemia (approximately 33% of patients in one study)
    • Chronic diarrhea
    • Nephrocalcinosis
    • Tetany: Neonatal tetany has been reported as a result of hypocalcemia.
  • In addition, congenital defects of the heart and major vessels are common and may require early surgical intervention.
  • Neuropsychological deficits include impairment in selective and executive visual attention, working memory, and sensorimotor function. Approximately 25% of children will develop schizophrenia in late adolescence or adulthood.

Physical

  • Characteristic facial features
    • Short philtrum
    • Low-set malformed ears
    • Hypertelorism
  • Other features
    • Micrognathia
    • Bifid uvula
    • Bowed mouth
  • Cardiac features
    • Truncus arteriosus
    • Septal defects
    • Abnormal aortic arch vessels (eg, interrupted aortic arch, double aortic arch, aberrant subclavian artery)
  • Neurologic features
    • Mental retardation
    • Calcification of the CNS
  • Renal features - Nephrocalcinosis
  • Ocular findings - Posterior embryotoxon, tortuous retinal vessels, eyelid hooding, strabismus, ptosis, and amblyopia5
  • Pulmonary features
    • Tracheoesophageal fistula
    • Short trachea with a reduced number of tracheal rings
    • Abnormal thyroid cartilage
    • Laryngomalacia
    • Tracheomalacia
    • Bronchomalacia

Causes

The deletion of chromosomal band 22q11, which results in monosomy 22q11, produces the developmental changes of DiGeorge syndrome.

  • Recent estimates suggest that the deletion of band 22q11.2 occurs in approximately 1 in 4000 live births.
  • Because the 22q11.2 deletion is present in most patients with the DiGeorge anomaly and a conotruncal anomaly face syndrome, these conditions are probably phenotypic variants of the same disorder.

More on DiGeorge Syndrome

Overview: DiGeorge Syndrome
Differential Diagnoses & Workup: DiGeorge Syndrome
Treatment & Medication: DiGeorge Syndrome
Follow-up: DiGeorge Syndrome
References
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References

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Further Reading

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Keywords

congenital thymic aplasia, third and fourth branchial pouch syndrome, CATCH-22 syndrome, DiGeorge anomaly and velocardiofacial syndrome,  conotruncal anomaly face syndrome, monosomy 22q11, severe combined immunodeficiency, severe combined immune deficiency, SCID

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Contributor Information and Disclosures

Author

Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine
Suguru Imaeda, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Connecticut State Medical Society, Sigma Xi, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other

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