Kabuki Syndrome (KS) is a rare genetic syndrome characterized by a typical facial gestalt, variable degrees of intellectual disability, organ malformations, postnatal growth retardation and skeletal abnormalities.

Unravelling molecular pathways shared by Kabuki and Kabuki-like syndromes:

Abstract

Kabuki Syndrome (KS) is a rare genetic syndrome characterized by a typical facial gestalt, variable degrees of intellectual disability, organ malformations, postnatal growth retardation and skeletal abnormalities. So far, KMT2D or KDM6A mutations have been identified as the main cause of KS, accounting for 56-75% and 3-8% of cases, respectively. Patients without mutations in one of the two causative KS genes are often referred to as affected by Kabuki-like syndrome. Overall they represent approximately 30% of KS cases, pointing towards substantial genetic heterogeneity for this condition. Here, we review all currently available Literature describing KS-like phenotypes (or phenocopies) associated with genetic variants located in loci different from KMT2D and KDM6A. We also report on a new KS phenocopy harboring a 5 Mb de novo deletion in chr10p11.22-11.21. An enrichment analysis aimed at identifying functional Gene Ontology classes shared by the two known KS causative genes and by new candidate genes currently associated with KS-like phenotypes primarily converges upon abnormal chromatin remodeling and transcriptional dysregulation as pivotal to the pathophysiology of KS phenotypic hallmarks. The identification of mutations in genes belonging to the same functional pathways of KMT2D and KDM6A can help design molecular screenings targeted to KS-like phenotypes.

Graphical Abstract

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