Kabuki syndrome (KS) is a rare multi-systemic disorder characterized by a distinct face, postnatal growth deficiency, mild-to-moderate intellectual disability, skeletal and visceral (mainly cardiovascular, renal, and skeletal) malformations, dermatoglyphic abnormalities. Its cause is related to mutations of two genes: KMT2D (histone-lysine N-methyltransferase 2D) and KDM6A (lysine-specific demethylase 6A), both functioning as epigenetic modulators through histone modifications in the course of embryogenesis and in several biological processes. Epigenetic regulation is defined as the complex of hereditable modifications to DNA and histone proteins that modulates gene expression in the absence of DNA nucleotide sequence changes. Different human disorders are caused by mutations of genes involved in the epigenetic regulation, and not surprisingly, all these share developmental defects, disturbed growth (in excess or defect), multiple congenital organ malformations, and also hematological and immunological defects. In particular, most KS patients show increased susceptibility to infections and have reduced serum immunoglobulin levels, while some suffer also from autoimmune manifestations, such as idiopathic thrombocytopenic purpura, hemolytic anemia, autoimmune thyroiditis, and vitiligo. Herein we review the immunological aspects of KS and propose a novel model to account for the immune dysfunction observed in this condition.
Keywords: Antibody deficiency; Autoimmunity; Epigenetic regulation; KDM6A (UTX); KMT2D (MLL2); Kabuki syndrome; Thrombocytopenia.