DiGeorge syndrome (22q11.2 deletion) is a multisystem disorder, and its management has advanced most notably in immunology and in the physiologic replacement of the hormones it disrupts. For the rare complete DiGeorge syndrome with athymia and profound T-cell deficiency, cultured thymus tissue transplantation (FDA-approved in 2021) restores thymopoiesis and naive T-cell development in almost all recipients, with graft failure and rejection rare. Newborn screening using the T-cell receptor excision circle (TREC) assay has improved early detection, allowing prompt immunologic evaluation — important because immune manifestations vary widely and partial DiGeorge syndrome can undergo spontaneous immune reconstitution.
Hypoparathyroidism is a core endocrine feature, and its treatment has been transformed: beyond conventional calcium and active vitamin D, palopegteriparatide (Yorvipath) — a once-daily prodrug of PTH(1-34) approved in 2024 — is the first true PTH replacement therapy for chronic hypoparathyroidism, restoring more physiologic PTH exposure and reducing reliance on high-dose calcium and vitamin D while sparing the kidneys. Research also implicates oxidative stress and neuroinflammation in the neurocognitive and psychiatric features of the syndrome, pointing to possible future targets. Care remains inherently multidisciplinary given the cardiac, developmental, immunologic, and endocrine involvement.
Further reading: thymus transplantation for DiGeorge syndrome (Ahmed et al., 2025); immunologic features and management of 22q11.2 deletion (Biggs et al., 2023); palopegteriparatide (Yorvipath) approval for hypoparathyroidism (2024).