Clinical and Immunological Characteristics of Kabuki Syndrome Patients with Autoimmune Cytopenias

Background Kabuki syndrome (KS) is a multisystem genetic disorder caused predominantly by pathogenic variants in KMT2D or KDM6A, characterized by developmental delay, congenital anomalies, and immune dysregulation. Autoimmune cytopenias are an important hematologic manifestation in KS; however, their clinical and immunological correlations remain insufficiently defined. This study aimed to compare the clinical and immunological features of KS patients with and without autoimmune cytopenias. Methods This multicenter study included all patients with Kabuki syndrome who met the international consensus diagnostic criteria for KS. A total of 51 patients with genetically or clinically confirmed KS were enrolled. Among them, 11 had autoimmune cytopenias (autoimmune thrombocytopenia, autoimmune hemolytic anemia, or both) and 40 did not. Clinical manifestations, immune parameters, and comorbidities were compared between groups. Continuous variables were compared using the t test, while categorical variables were analyzed using the chi-square test. Results Patients with cytopenias were significantly older at diagnosis compared to those without cytopenias (10.5 ± 7.5 vs. 3.4 ± 4.9 years, p = 0.005). Gender distribution did not differ significantly between groups (p = 0.477). Hearing impairment was significantly more prevalent in patients without cytopenias (65.8%) than in those with cytopenias (18.2%) (p = 0.005). Conversely, hypogammaglobulinemia was markedly more common among patients with cytopenias (70%) compared to those without (22.9%) (p = 0.005). No statistically significant differences were observed in the prevalence of congenital cardiac abnormalities or endocrinopathies between the two groups. Regarding lymphocyte subsets, B cell lymphopenia and natural killer (NK) cell lymphopenia were significantly more frequent in the cytopenias group (33.3% vs. 6.7% for both, p = 0.036). Although T cell lymphopenia was more common in patients with cytopenias (55.6% vs. 30%), this difference did not reach statistical significance (p = 0.161). Conclusion Approximately 20% of KS patients exhibit autoimmune cytopenias. Autoimmune cytopenias in KS are associated with a higher frequency of hypogammaglobulinemia and B cell lymphopenia, indicating a more pronounced underlying immune dysfunction. These findings highlight the importance of proactive immunological evaluation and monitoring in KS patients presenting with cytopenias. Tabular data are included as downloadable supplement files.