Abstract
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.