Clinical phenotype and diagnostic pathways of 22q11.2 deletion syndrome in a Ukrainian cohort

Introduction Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a common multisystem genomic disorder with marked phenotypic variability and diagnostic delay. Data on diagnostic pathways and specialist involvement in Eastern Europe remain limited. We aimed to characterize diagnostic pathways and clinical triggers, assess specialist involvement and follow-up, and identify factors associated with diagnosis before or after 1 year of age in a Ukrainian cohort. Methods We conducted a retrospective multicenter observational study of patients with 22q11.2DS registered in the Ukrainian National Registry of Primary Immunodeficiencies. Clinical manifestations, diagnostic triggers, specialists involved in diagnosis and follow-up, immunological findings, and age at diagnosis were analyzed. Results The cohort included 126 patients, with a median age of 12 years (range, 0.1–39 years) and median age at diagnosis of 1.0 year (range, 0.1–18 years). Among 120 patients with available diagnostic timing, 63 (52.5%) were diagnosed within the first year, including the two antenatal cases. Congenital heart disease (CHD) was the most frequent major manifestation (74/89, 83.1%), followed by craniofacial dysmorphism (62/74, 83.8%), thymic hypoplasia (54/65, 83.1%), developmental delay (46/62, 74.2%), and recurrent infections (44/65, 67.7%). Among 83 patients with documented diagnostic triggers, CHD was the most frequent (61/83, 73.5%). Developmental delay was more frequent among patients diagnosed after 1 year than within the first year (22.9% vs. 4.4%, p = 0.0135). Immunodeficiency was a diagnostic trigger in 10/83 patients (12.0%), despite T-cell lymphopenia in 31/59 (52.5%). Immunologists and geneticists were most frequently involved in diagnosis. Cardiothoracic surgeons and cardiologists were more frequently involved among patients diagnosed within the first year than after 1 year (27.9% vs. 9.1%, p = 0.0411). Among 13 patients diagnosed after implementation of TREC/KREC newborn screening, two were identified following an abnormal screening result. Conclusions In this Ukrainian cohort, 22q11.2DS diagnosis was predominantly phenotype-driven, with CHD representing the principal diagnostic trigger. Developmental delay was associated with diagnosis after 1 year, whereas immunological abnormalities relatively infrequently initiated diagnostic evaluation. Broader recognition of non-cardiac presentations, standardized referral criteria, coordinated multidisciplinary care, and continued development of newborn and prenatal screening may improve timely diagnosis of 22q11.2DS in Ukraine.