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DiGeorge Syndrome

(22q11.2 Deletion Syndrome)

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Last full review/revision Dec 2019| Content last modified Dec 2019
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DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell immunodeficiency and hypoparathyroidism. Infants with DiGeorge syndrome have low-set ears, midline facial clefts, a small receding mandible, hypertelorism, a shortened philtrum, developmental delay, and congenital heart disorders. Diagnosis is based on clinical findings and includes assessments of immune and parathyroid function and chromosome analysis. Treatment includes supportive measures and, if severe, thymus or stem cell transplantation.

DiGeorge syndrome is a primary immunodeficiency disorder that involves T cell defects. It results from gene deletions in the DiGeorge chromosomal region at 22q11, mutations in genes at chromosome 10p13, and mutations in other unknown genes, which cause dysembryogenesis of structures that develop from pharyngeal pouches during the 8th week of gestation. Most cases are sporadic; boys and girls are equally affected.

DiGeorge syndrome may be

  • Partial: Some T-cell function exists

  • Complete: T-cell function is absent

Symptoms and Signs

Infants with DiGeorge syndrome have low-set ears, midline facial clefts, a small receding mandible, hypertelorism, a shortened philtrum, developmental delay, and congenital heart disorders (eg, interrupted aortic arch, truncus arteriosus, tetralogy of Fallot, atrial or ventricular septal defects). They also have thymic and parathyroid hypoplasia or aplasia, causing T-cell deficiency and hypoparathyroidism.

Recurrent infections begin soon after birth, but the degree of immunodeficiency varies considerably, and T-cell function may improve spontaneously. Hypocalcemic tetany appears within 24 to 48 hours of birth.

Prognosis often depends on severity of the heart disorder.

Diagnosis

  • Immune function assessment with immunoglobulin (Ig) levels, vaccine titers, and lymphocyte subset counts

  • Parathyroid function assessment (see Hypocalcemia)

  • Chromosome analysis

Diagnosis of DiGeorge syndrome is based on clinical findings.

An absolute lymphocyte count is done, followed by B- and T-cell counts and evaluation of lymphocyte subsets if leukopenia is detected; blood tests to evaluate T-cell and parathyroid function are done. Ig levels and vaccine titers are measured. If complete DiGeorge syndrome is suspected, the T-cell receptor excision circle (TREC) test should also be done.

A lateral chest x-ray may help evaluate thymic shadow.

Fluorescent in situ hybridization (FISH) testing can detect the chromosomal deletion in the 22q11 region; standard chromosomal tests to check for other abnormalities may also be done.

If DiGeorge syndrome is suspected, echocardiography is done. Cardiac catheterization may be necessary if patients present with cyanosis.

Because most cases are sporadic, screening of relatives is not necessary.

Treatment

  • Partial syndrome: Calcium and vitamin D supplementation

  • Complete syndrome: Transplantation of cultured thymus tissue or hematopoietic stem cells

In partial DiGeorge syndrome, hypoparathyroidism is treated with calcium and vitamin D supplementation; long-term survival is not affected.

Complete DiGeorge syndrome is fatal without treatment, which is transplantation of cultured thymus tissue or hematopoietic stem cell transplantation. A recent review of thymus transplantation has shown relatively good results with T cell reconstitution by 5 to 6 months (1).

Treatment reference

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