DIAGNOSIS AND MANAGEMENT OF AN INFANT WITH ATYPICAL COMPLETE DIGEORGE IMMUNOLOGIC PHENOTYPE

Abstract

Introduction The diagnosis of complete DiGeorge syndrome is seen ≤1.5% of patients with 22q11.2 syndrome. We present a rare case of an infant with CHARGE syndrome with atypical complete DiGeorge immunologic phenotype. Case Description A 3-day old Caucasian male was referred for absent TRECs for SCID. He had known arch hypoplasia prior to delivery. Following delivery, a tracheoesophageal fistula was identified. Additional congenital anomalies included large patent ductus arteriosus, bilateral iris colobomas, dysplastic ears, microphallus, cryptorchidism, and bilateral hydronephrosis. His initial lymphocyte enumeration demonstrated absent T-cells, normal number of B-cells and NK-cells. Lymphocyte proliferation to mitogens was absent. Targeted sequencing demonstrated a new variant in CHD7c.2698-11A>G predicted to affect splicing. SCID genetic panel and chromosomal microarray were normal. Based on workups and congenital anomalies, he was diagnosed with CHARGE syndrome with a complete DiGeorge phenotype. At 5 months of age, he developed Omenn syndrome-like manifestations with diffuse non-blanching erythematous macular rash over his body. Serial lymphocyte subsets demonstrated the development of T-cells expressing HLA-DR indicating the emergence of activated T-cells (CD3 269/cumm; CD3+HLA-DR 258/cumm, 96% of total T-cells). Spectratyping confirmed the presence of oligoclonal-T-cells. Therefore, immunosuppression with cyclosporin and prednisolone was given for treatment of self-reactive oligoclonal-T-cells with resolution of rashes. He is currently awaiting thymus transplantation, and receiving IVIG, and antimicrobial prophylaxis. Discussion Although not yet approved by FDA, thymus transplantation is the preferred treatment for complete DiGeorge syndrome. Additionally, close monitoring of activated self-reactive oligoclonal-T-cells symptoms with proper immunosuppressive treatment is crucial while patient is waiting for thymus transplantation.