22q11.2 Deletion Syndrome and Immune Dysregulation: A Case Report

The 22q11.2 deletion syndrome is a multisystemic genetic disorder characterized by a broad spectrum of clinical manifestations, including congenital heart defects, palatal anomalies, neurodevelopmental disorders, and immunodeficiencies. In rare cases, it may be associated with immune dysregulation, including autoimmunity and lymphoproliferation, which, combined with immunodeficiency, predispose patients to severe infections and poor response to treatment.

We report a 4-year-old female with a history of surgical closure of a patent ductus arteriosus at 1 year, psychomotor developmental delay, and viral pneumonia requiring mechanical ventilation. At 2 years, she developed bicytopenia (hemoglobin 8.7 g/dL, platelets 6 × 10³/μL), a positive direct Coombs test, and splenomegaly. Leukemia was excluded by bone marrow aspirate and molecular studies. Flow cytometry revealed marked reductions in CD4⁺ naïve (76/μL), CD8⁺ naïve (70/μL), and TCRγδ⁺ CD4^-CD8^- cells (8/μL). Immunological studies showed IgG 1,264 mg/dL, IgM 314 mg/dL, IgA 86 mg/dL, C3 73 mg/dL, and C4 11 mg/dL. Genetic testing identified a 22q11.2 deletion and a variant of uncertain significance in the TLR8 gene. She was started on prednisone and mycophenolate, achieving partial response. At 4 years, she was readmitted with pancytopenia (leukocytes 3.94 × 10³/μL, hemoglobin 3.1 g/dL, platelets 47 × 10³/μL) and septic shock secondary to bacterial pneumonia, requiring intensive care unit admission, broad-spectrum antibiotics, vasopressors, and intravenous immunoglobulin. Imaging revealed multiple cervical and peritoneal lymphadenopathies and hepatosplenomegaly. Additionally, positive antiplatelet antibodies were detected. Despite immunosuppressive therapy, she exhibited persistent cytopenias and incomplete hematologic response to date.

This case illustrates a severe and atypical presentation of immune dysregulation in 22q11.2 deletion syndrome, manifesting as immunodeficiency, autoimmune cytopenias, and lymphoproliferation. The findings underscore the importance of early immunological and genetic evaluation in patients with refractory cytopenias and recurrent severe infections. Conventional immunosuppressive therapy may be insufficient, requiring tailored strategies in complex cases.