Immunodeficiency in CHARGE syndrome

Abstract

Immunodeficiency can occur in CHARGE syndrome, with immunophenotypes including reduction in T‐cell counts, combined T‐B cell defects rarely requiring antibiotic prophylaxis or immunoglobulin replacement, and severe combined immunodeficiency, which is fatal without immune reconstitution. However, the prevalence of immunodeficiency in CHARGE syndrome remains unclear with few prospective studies. In this review, we examine the existing literature covering immunodeficiency associated with CHARGE syndrome, compare these with immunodeficiencies reported in 22q11.2 deletion syndrome (a condition that shares many phenotypic characteristics with CHARGE syndrome) and suggest future research priorities.

T-Cell Immunodeficiencies With Congenital Alterations of Thymic Development: Genes Implicated and Differential Immunological and Clinical Features

“…They may show severe T-cell deficiency resembling SCID or, similarly to DGS, they may present transient lymphopenia, that usually normalizes over time. A close association between lymphopenia and hypocalcemia has been identified (115). Severity of the T-cell lymphopenia relates to the degree of thymic hypoplasia (127).…”

“…Naive CD4 and CD8 lymphocytes are lower in pDGS patients compared to controls independently of age and they decline more rapidly with age (78). The improvement of the lymphopenia with age is not due to a recovery of the thymic function but to the peripheral homeostatic expansion of the available T cells, as suggested by the evidence that T cells are predominantly or almost exclusively of a memory phenotype, TRECs are low and the repertoire is oligoclonal (78,115,116). T-cell proliferation, total immunoglobulins, and specific antibody response to vaccines are typically normal.…”

Establishment of immunity against Epstein‐Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion

“…Recent reports have demonstrated that there is a significant prevalence of immunodeficiency among CHARGE syndrome patients, which may occasionally be fatal, especially in patients who share symptoms with cDGS. 6 Choices of treatment for immunodeficiency in cDGS include stem cell transplantation, cord blood transplantation, or G-CSF-induced peripheral blood stem cell transplantation, peripheral blood lymphocyte transfusion, and thymus transplantation. Although thymus transplantation shows better survival rates (75%) 7 than others (41%), 9 it is not universally available and is not approved in Japan due to ethical issues.…”

“…These two congenital disorders are not mutually exclusive. It has been reported that the clinical manifestations sometimes overlap between CHARGE syndrome and DGS …”

“…It has been reported that the clinical manifestations sometimes overlap between CHARGE syndrome and DGS. 5,6 Definitive treatment of cDGS is transplantation of allogeneic thymus tissue, 7 but this technique is not universally available.…”