Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients

Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives. From a cohort of 1802 patients with paediatric-onset autoimmune cytopenia (AIC), 11 pathogenic variants in the KMT2D gene were identified, with three cases detected during this AIC genetic work-up. Three patients had variants of unknown significance; this underscores challenges in NGS interpretation using both genetic and clinical data integration. Recognizing KS in paediatric or adult patients with AIC is crucial for appropriate management and follow-up. Those rare patients may benefit from rituximab, mycophenolate mofetil or rapamycin.image