Deletion Syndrome (Digeorge Syndrome)

Deletion Syndrome (Digeorge Syndrome): Excerpt from The 5-Minute Pediatric Consult

Erin E. McGintee, MD

Deletion Syndrome - BASICS

Deletion Syndrome - description

Deletion syndrome, which is more commonly known as DiGeorge syndrome is characterized by thymic and parathyroid aplasia or hypoplasia, cardiac outflow tract abnormalities, cleft palate, velopharyngeal insufficiency, and facial dysmorphism. T-cell immunodeficiency is observed in 80% of children with DiGeorge syndrome:

• Patients with complete DiGeorge syndrome have a severe T-cell defect.
• Partial DiGeorge syndrome occurs when the T-cell defect is partial or transient.

Deletion Syndrome - risk factors

Deletion Syndrome - genetics

• Heterogeneous
• 6–10% of cases are familial
• Most common associated chromosomal abnormalities are heterozygous microdeletions of 22q11.2.

Deletion Syndrome - pathophysiology

DiGeorge is believed to be a developmental defect of the 3rd and 4th pharyngeal arches.

Deletion Syndrome - DIAGNOSIS

Deletion Syndrome - signs & symptoms

Deletion Syndrome - history

• Neonatal hypocalcemia secondary to hypoparathyroidism
• Recurrent viral and opportunistic infections: Diarrhea, candidiasis, respiratory infections, Pneumocystis carinii (PCP)
• Cardiac defects, particularly interrupted aortic arch, septal defects, tetralogy of Fallot, and truncus arteriosus
• Failure to thrive

Deletion Syndrome - physical exam

Facial dysmorphism (micrognathia; low, rotated ears; fish-shaped mouth; short philtrum, anteverted nares, broad nasal bridge and hypertelorism):

• Cleft lip and palate
• Heart murmur
• Renal abnormalities
• Skeletal abnormalities
• Central nervous system malformations
• Cognitive/Behavioral disorders
• Major immunologic features present at birth: Lymphopenia, T-cell dysfunction; antibody levels and function are variable.

Deletion Syndrome - tests

Deletion Syndrome - lab

• CBC with differential:
  • Immediately after birth, a lymphocyte count of <1,200/mm³ is suspicious
  • Serum calcium
  • Evaluation of parathyroid function, if necessary
• Lymphocyte markers:
  • To determine absolute numbers of T and B cells and their subsets
• Mitogen studies:
  • To study the functional abilities of T and B cells. In DiGeorge syndrome, you may see a variably depressed response to phytohemagglutinin, concanavalin A, and pokeweed mitogen.
• Quantitative immunoglobulins (IgG, IgA, IgM, and IgE):
  • Often the humoral system will be abnormal if there is helper T-cell dysfunction.
• Fluorescence in situ hybridization (FISH) for 22q11 deletion:
  • Most common chromosomal defect

Deletion Syndrome - imaging

• Chest radiograph study
• To evaluate for cardiac malformation and also for the presence of a thymic shadow

Deletion Syndrome - TREATMENT

Deletion Syndrome - general measures

• Depending on the defects or deficiencies the child manifests, some issues may need to be addressed:
  • Cardiology for the cardiac malformations
  • Otolaryngology and feeding specialist for cleft palate
  • Endocrinology for follow-up of hypoparathyroidism
  • Speech and cognitive intervention for speech delay
  • Immunology to monitor T-cell disorder and recurrent infections
  • Severe immunodeficiency may require matched sibling bone marrow transplant or thymic transplant.
• Special consideration with infections: Children with the complete DiGeorge syndrome are at increased risk of morbidity and mortality from viral infections either from vaccines such as oral polio or natural infections such as varicella:
  • Avoid live viral vaccines in cases of T-cell dysfunction. These patients may need immunoglobulin replacement therapy to protect from infections.
  • Consider varicella immune globulin in a patient either with unknown humoral immunity status or definitive humoral abnormalities and a history of exposure. IV acyclovir may be necessary if varicella develops and patient has a low T-cell count or abnormal mitogens.
• Special consideration with blood transfusions:
  • Because these patients are at risk for graft-versus-host disease, it is best to use cytomegalovirus-negative, irradiated blood.

Deletion Syndrome - FOLLOW UP

Deletion Syndrome - prognosis

Prolonged survival is seen in most patients after the spontaneous improvement of T-cell numbers and function. Patients with complete DiGeorge syndrome may have more severe and persistent T-cell dysfunction. Complications may include an increase in autoimmune phenomena and neurologic sequelae.

Deletion Syndrome - complications

In the newborn period, patients present with hypocalcemic tetany, manifestation of cardiac abnormality, and recurrent infections. Later on, patients present more commonly with neurologic and developmental or behavioral issues.

• Monitor growth
• Monitor hearing

Deletion Syndrome - bibliography

Ballow M, O’Neil KM. Approach to the patient with recurrent infections. In: Adkinson NF, Yunginger JW, Busse WW, et al., eds. Middleton’s Allergy Principles and Practice. 6th ed. Philadelphia: Mosby; 2003:1057–1058.
1. Goldmuntz E. DiGeorge Syndrome: New Insights. Clin Perinatol. 2005;32(4):963–978.
Notarangelo LD. T cell immunodeficiencies. In: Leung DYM, Sampson HA, Geha RS, et al., eds. Pediatric Allergy Principles and Practice. St. Louis, MO: Mosby; 2003:104–105.
2. Perez E, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes). Curr Opin Pediatr. 2002;14:678–683.
3. Radford DJ. The DiGeorge syndrome and the heart. Curr Opin Pediatr. 1991;3:828–831.
4. Sullivan KE. DiGeorge syndrome/chromosome 22q11.2 deletion syndrome. Curr Allergy Asthma Rep. 2001;1(Sep):438–444.
Sullivan KE. DiGeorge Syndrome and Chromosome 22q11.2 Deletion Syndrome. In: Stiehm ER, Ochs HD, Winkelstein JA, eds. Immunologic Disorders in Infants and Children. 5th ed. Philadelphia: El Sevier Saunders; 2004:523–530.

Deletion Syndrome - CODES

Deletion Syndrome - icd9

279.11 DiGeorge syndrome

Deletion Syndrome - FAQ

• Q: Is there a definitive test to distinguish between partial and complete DiGeorge syndrome?
• A: Over time, patients with partial DiGeorge syndrome will reconstitute their T cells and acquire improved function based on mitogen and antigen studies.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About DiGeorge's syndrome

• Back to disease: DiGeorge's syndrome: Introduction
• Next Book Extract About DiGeorge's syndrome: Pharyngitis (The 5-Minute Pediatric Consult)
• More Book Extracts: All Online Books for DiGeorge's syndrome

More Medical Textbooks Online about DiGeorge's syndrome

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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