Congenital Athymia: from Genetic Causes to Advanced Therapeutic Approaches

Congenital athymia is an extremely rare disorder characterized by the absence of a functioning thymus at birth, resulting in profound immunodeficiency. This immunodeficiency is caused by the lack of T cell development, leading to increased susceptibility to infections and the risk of autologous graft-versus-host disease due to extrathymic T cell production. The condition is often associated with genetic and syndromic disorders, including FOXN1 deficiency, 22q11.2 deletion syndrome, CHARGE syndrome, and complete DiGeorge syndrome. Thymus transplantation has emerged as the most effective treatment, particularly when performed early to improve immune reconstitution and reduce the risk of infections. Supportive care, including antimicrobial prophylaxis, immunoglobulin replacement therapy, and close monitoring for viral infections, is essential while awaiting transplantation. The present review article focuses on clinical manifestations, aetiology, pathophysiological consequences, management strategies and economic burden of congenital athymia