DiGeorge Syndrome (DGS)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU


Combined Immunodeficiencies (click to enlarge the image).

Deletion of 22q11.2 is the cause of DGS in 90% of cases. Hypocalcemia that results from the hypoparathyroidism can result in seizures. There are wide clinical variations of DGS.

DGS is due to dysmorphogenesis of the 3rd and 4th pharyngeal pouches which leads to thymic and parathyroid aplasia or hypoplasia . DGS can be partial or complete, depending on the degree of thymic hypo/aplasia . Microdeletions at 22q11.2 are the most common cause. DGS is rarely familial.

The lack of thymus in DGS leads to a lack of T-cell differentiation. DGS manifests with decreased cellular immunity which leads to an increased susceptibility to certain fungal, viral and bacterial infections. The B-cell function is also affected due to the lack of helper cells.

Features of complete DGS

Micrognathia
Hypertelorism
Low-set malformed ears
Short Philtrum
Fish shaped mouth
Thymic aplasia or hypoplasia, congenital heart disease, hypoparathyroidism
Absent thymus shadow

DiGeorge syndrome: part of CATCH 22

DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22q11.

DiGeorge syndrome should be seen as the severe end of the clinical spectrum embraced by the acronym CATCH 22 syndrome:

Cardiac defects
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcaemia resulting from 22q11 deletions.

Patients with complete DiGeorge syndrome typically do not have a thymic shadow on chest X-ray.

Treatment of DiGeorge Syndrome

No treatment is needed for children with the partial form. DGS has a generally good prognosis if there are no major cardiac anomalies.

The transplant of thymic epithelial explants from HLA-matched donors has reconstituted immune function in some patients with complete DiGeorge syndrome.

Conditions with elevated IgE

Atopic dermatitis, Asthma, ABPA, and allergic fungal sinusitis

Infections (parasites, HIV, TB, EBV, and CMV)

Malignancy (IgE myeloma and lymphoma)

Churg-Strauss syndrome

Kimura’s disease, painless, unilateral cervical lymphadenopathy or subcutaneous masses in the head or neck region

Immunodeficiency diseases with elevated IgE

Hyper IgE syndrome (HIES)

Wiskott-Aldrich syndrome (WAS)

Omenn syndrome

DiGeorge syndrome (DGS)

Netherton syndrome, form of ichthyosis associated with SPINK5

Nezelof syndrome, congenital hypoplasia of the thymus with retention of normal parathyroid function (in contrast to complete DiGeorge syndrome in which there is absence of the parathyroids)

References

DiGeorge syndrome: part of CATCH 22. Wilson DI, Burn J, Scambler P, Goodship J. J Med Genet. 1993 Oct;30(10):852-6.

Published: 08/29/2009
Updated: 12/03/2012