DiGeorge Syndrome (22q11.2 Deletion Syndrome)

Key Features

• Congenital heart defects

• Hypocalcemia and seizures

• Distinctive craniofacial features

• Thymic hypoplasia

• Incidence is about 1:4000 births

• Associated immunodeficiency is secondary to the aplastic or hypoplastic thymus

• Most patients have no or only mild immune defects

• The term partial DiGeorge syndrome is commonly applied to patients with impaired rather than absent thymic function

Clinical Findings

• Clinical characteristics include congenital heart defects, hypocalcemia due to hypoparathyroidism, distinctive craniofacial features, renal anomalies, and thymic hypoplasia

• Presentation usually results from cardiac failure or from hypocalcemia 24–48 hours postpartum

• Infections commonly present as recurrent ear-nose-throat infections

• Additional important clinical issues include delayed speech, cognitive impairment, and behavioral problems

• Risk of developing schizophrenia and autoimmune disorders in increased in these patients

Diagnosis

• Laboratory evaluation typically reveals normal to decreased numbers of T lymphocytes with preserved T-lymphocyte function and normal B-lymphocyte function

• In the rare patient with absent or dysfunctional T lymphocytes, B-lymphocyte function and antibody production may be abnormal

• Over time, T-lymphocyte numbers normalize in the majority of patients who have low numbers of T lymphocytes at initial presentation

• Fluorescence in situ hybridization (FISH) chromosomal analysis for the microdeletion on chromosome 22, or microarray-based comparative genomic hybridization confirms diagnosis

Treatment

• Surgery may be required for cardiac defects

• Vitamin D, calcium, or parathyroid hormone replacement to correct hypocalcemia and treat seizures may be needed

• Transfusion products should be irradiated

• Both thymic grafts and BMT have been used successfully in patients with absent T-lymphocyte immunity

• T-cell numbers and function should be assessed before administration of vaccine to avoid side effects