22q11.2 deletion syndrome (DS) is the second most common cause of congenital heart disease (CHD) and a multisystem disorder that contributes to substantial overall disease burden. Additionally, 22q11.2DS is the most common cause of DiGeorge syndrome and the second most common chromosomal abnormality after Down syndrome, found in 1/2,148 live births. Up to 75–80% of 22q11.2DS patients have immune system abnormalities. We aim to determine whether CHD complexity is associated with a higher burden of allergic, immunologic, and autoimmune diagnoses.
We performed a retrospective chart review of adults (>18 years) with confirmed 22q11.2DS seen at the 22q and You Center at Children’s Hospital of Philadelphia (CHOP). Exclusion criteria included 22q11.2 duplication, residence more than 100 miles from CHOP, and no documented visit between 2001 and 2025. We assessed CHD severity (based on structural complexity) and its association with allergic, immunologic, and autoimmune disorders identified through diagnosis codes. These variables were compared by chi-square analysis.
A total of 419 adults met the inclusion criteria; 54 of 419 (13%) had a documented autoimmune diagnosis, 118 (28%) had an allergic condition, and 121 (29%) had an immune disorder. Twenty-five patients (6%) had an unknown cardiac history—so presumed normal/mild CHD. Of those with CHD, 37 individuals (9%) had a documented autoimmune diagnosis, 75 (18%) had an allergic diagnosis, and 87 (21%) had an immune condition.
Analysis of CHD complexity revealed no statistically significant association with lifetime autoimmune diagnoses (p = 0.08) or allergic diagnoses (p = 0.32). In contrast, CHD complexity was significantly associated with immune diagnoses (p = 0.001), suggesting that individuals with more structurally complex congenital heart disease experience a higher burden of immune-related conditions over their lifetime.
These findings highlight a potential link between cardiac severity and immune system involvement in adults with 22q11.2DS, underscoring the importance of longitudinal cardiovascular and immunologic care in this population.
