From Thymic Hypoplasia to Immune Reconstitution: An Immunological Review of DiGeorge Syndrome

DiGeorge syndrome (DGS), also known as 22q11.2 deletion syndrome, is the most prevalent chromosomal microdeletion syndrome. It presents with a heterogeneous phenotype and diverse clinical manifestations, which may include, but are not limited to, cardiovascular, endocrine, neurodevelopmental and immune function abnormalities. The immune defects seen in individuals with DGS arise from impairment in thymus development, resulting in immune dysregulation. This thymic dysfunction impairs T-cell development and maturation, leading to a spectrum of T-cell lymphopenia, a restricted T-cell receptor repertoire and defects relating to regulatory T cells. Consequently, patients exhibit increased susceptibility to recurrent infections, particularly of the respiratory tract and a higher prevalence of autoimmune conditions and atopic diseases. The present literature review synthesises current knowledge on the immunopathogenic mechanisms, clinical manifestations and treatment approaches for the immune dysregulation in DGS.