Clinical and Immunological Defects and Outcomes in Patients with Chromosome 22q11.2 Deletion Syndrome

Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans and can present with highly variable clinical manifestations. Immune deficiencies occur because of thymic hypoplasia or aplasia.

Methods: This retrospective study included patients diagnosed with 22q11.2DS at a medical center between 2000 and 2021. We analyzed the association between clinical phenotypes, immunological abnormalities, age, and outcomes.

Results: Eighty-seven patients with 22q11.2DS had a median diagnostic age of 1.78 months. Patients presented with congenital heart disease (CHD; 86.2%), major infections (75.9%), and failure to thrive (FTT; 58.6%). Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Neonatal seizures were associated with early diagnosis before 2 months (OR 8.56, 95% CI 1.21-60.58, P = 0.032). Immunological abnormalities included lymphopenia (93.1%), T lymphopenia (71.9%), CD4⁺ T lymphopenia (64.1%), a lack of hepatitis B vaccine antibodies (46.2%), and complete DiGeorge syndrome (cDGS) (2.3%). Severe lymphopenia and T lymphopenia improved at 3 years of age. Two patients with cDGS were treated with hematopoietic stem cell transplantation, and one survived. The mortality rate was 12.8% and the estimated 35-year survival probability was 77.5%. Major infections experienced > four times were significantly associated with a decreased survival rate of 60%. Patients with CHD without FTT or recurrent infections had a better 20-year survival rate (96.2%).

Conclusions: CHD, major infection, and FTT were common manifestations and poor prognostic factors. Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Although T lymphopenia may improve with age, patients with 22q11.2DS require lifelong monitoring for immune dysregulation.