Kabuki syndrome (OMIM: 147920) is a rare condition, mainly associating intellectual deficiency, a polymalformative syndrome, and specific morphological changes in the face. It nevertheless has a strong clinical and biological heterogeneity with rarer but very different symptoms (endocrinological anomalies, autoimmune disorders, obesity, etc.). Clinical diagnosis is difficult because it is based on a spectrum of clinical, radiological, and biological factors. Complications are numerous, sometimes interpenetrating, and early diagnosis of the disease is essential for optimal management. The development of genetic testing is therefore essential for the diagnosis of this disease. Recently, exome sequencing has helped identify two genes responsible for the disease: KMT2D (lysine (K)-specific methyltransferase 2D, better known as MLL2 - mixed lineage leukemia), and KDM6A (lysine-specific demethylase 6A). Functional studies of these genes should help clarify their role in the pathogenesis of the disease, in particular to test the hypothesis of epigenetic changes during embryogenesis and development. Finally, understanding the interactions between KMT2D and its target genes could unravel other candidate genes for hitherto unexplained Kabuki syndrome cases.
