Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome

Abstract

The clinical features of 22q11.2 deletion syndrome include virtually every organ of the body. This review will focus on the immune system and the differences related to deletion breakpoints. A hypoplastic thymus was one of the first features described in this syndrome and low T cell counts, as a consequence of thymic hypoplasia, are the most commonly described immunologic feature. These are most prominently seen in early childhood and can be associated with increased persistence of viruses. Later in life, evidence of T cell exhaustion may be seen and secondary deficiencies of antibody function have been described. The relationship of the immunodeficiency to the deletion breakpoints has been understudied due to the infrequent analysis of people carrying smaller deletions. This manuscript will review the immune deficiency in 22q11.2 deletion syndrome and describe differences in the T cell counts related to the deletion breakpoints. Distal, non-TBX1 inclusive deletions, were found to be associated with better T cell counts. Another new finding is the relative preservation of T cell counts in those patients with a 22q11.2 duplication.

Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome

“…Smaller deletions bracketed by the other LCRs have overlapping clinical features. We studied the deletion size as a predictor of immune deficiency and found that the deletion of TBX1 was associated with the immunodeficiency . The distal deletions that do not include TBX1 and the duplications appear to be largely spared the immunodeficiency.…”

“…We therefore examined the association of cardiac anomalies to T cell count in infants with 22q11.2del and found there was no relationship between the complexity of the cardiac anomaly and the T cell count . We also examined deletion size as an independent driver of T cell lymphopenia . Deletion size was not critical but inclusion of the gene TBX1 in the deletion was associated with worse T cell counts.…”

“…We studied the deletion size as a predictor of immune deficiency and found that the deletion of TBX1 was associated with the immunodeficiency. 41 The distal deletions that do not include TBX1 and the duplications appear to be largely spared the immunodeficiency. TBX1, encoding a T-box transcription factor, has been the gene implicated most strongly in the overall phenotype using murine knockouts with overlapping deletions.…”

“…106 We also examined deletion size as an independent driver of T cell lymphopenia. 41 Deletion size was not critical but inclusion of the gene TBX1 in the deletion was associated with worse T cell counts.…”

Outcomes of truncus arteriosus repair and predictors of mortality

“…The main characteristics observed in this syndrome are dysmorphic facial features, velophrayngeal abnormlaities, conotruncal cardiac defects, immunodeficiency, thymic insufficiency, hypoparthyroidisim, and developmental delays 7 . We hypothesize that having 22q11.2 deletion syndrome would influence the resource utilization in the postoperative period, as these subjects would have a prolonged and more complicated postoperative course given the presence of immunodeficiency and multiple noncardiac anomalies that are associated with 22q11.2 deletion syndrome 8 …”