D3.367 - Clinical and immunological heterogeneity of 22q11.2 deletion syndrome in children from the Republic of Moldova

22q11.2 deletion syndrome (22q11.2DS) is a prototypical inborn error of immunity caused by abnormal thymic development and characterized by marked clinical and immunological variability. Data from Eastern Europe, including the Republic of Moldova, remain limited, particularly regarding immune-related morbidity.

Aim

To describe the clinical and immunological spectrum of pediatric 22q11.2DS in a single-country Eastern European cohort and to explore the association between immunological abnormalities and infection burden.

We conducted a descriptive observational study including 10 genetically confirmed pediatric patients with 22q11.2DS followed at a national tertiary center. Clinical manifestations, congenital anomalies, and immunological parameters (lymphocyte counts, immunoglobulin levels, thrombocyte counts, and thymic status) were analyzed. Genetic confirmation was performed using droplet digital PCR (ddPCR) and fluorescence in situ hybridization (FISH). Exploratory statistical analyses were applied to assess associations between infections and immunological findings, using Fisher’s exact test and odds ratios (OR).

The cohort included 70% females, with a median age at diagnosis of 17 months; 40% were diagnosed within the first year of life. Recurrent respiratory infections occurred in 40% of patients, mainly pneumonia. Thymic aplasia or hypoplasia was documented in 60%. Children with thymic aplasia had increased odds of infections (OR 3.0), although this association did not reach statistical significance (Fisher exact test, p=0.52). No significant association was observed between lymphopenia and infections (p=1.0), likely reflecting limited statistical power. Infection frequency decreased following corrective cardiac surgery. Congenital heart disease was present in 90%. Immunological abnormalities were heterogeneous, including lymphopenia (30%), thrombocytopenia (20%), IgA deficiency (10%), and elevated IgE levels (20%). Neurodevelopmental delay and speech impairment affected 40%, while facial dysmorphism was present in 90%. 

This cohort from the Republic of Moldova highlights the pronounced clinical and immunological heterogeneity of 22q11.2DS. Although exploratory analyses did not demonstrate statistically significant associations, observed trends support a biologically plausible link between thymic abnormalities and infection susceptibility. Early genetic diagnosis combined with longitudinal immunological monitoring is essential to optimize patients’ care.