Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms

World J Pediatr. 2019 Dec;15(6):528-535. doi: 10.1007/s12519-019-00309-4. Epub 2019 Oct 5.


Background: Kabuki syndrome (KS), is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase (KMT2D) or an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A). The characteristics in patients with KS have not yet been well recognized.

Data sources: We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome. The most relevant articles to the scope of this review were chosen for analysis.

Results: Clinical diagnosis of KS is challenging in initial period, because many clinical characteristics become apparent only in subsequent years. Recently, the genetic and functional interaction between KS-associated genes and their products have been elucidated. New clinical findings were reported including nervous system and intellectual performance, endocrine-related disorders and immune deficiency and autoimmune disease. Cancer risks of Kabuki syndrome was reviewed. Meanwhile, we discussed the Kabuki-like syndrome. Digital clinical genetic service, such as dysmorphology database can improve availability and provide high-quality diagnostic services. Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk, efforts in the research for new mechanisms are thus of maximum interest.

Conclusions: Kabuki syndrome has a strong clinical and biological heterogeneity. The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and -off of the chromatin. The direction of drug research may be to regulate the normal opening of chromatin. Small molecule inhibitors of histone deacetylases maybe helpful in treatment of mental retardation and reduce cancer risk in KS.

Keywords: Cancer risk; KDM6A; KMT2D; Kabuki syndrome; Kabuki-like syndrome.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Child
  • Epigenesis, Genetic*
  • Face / abnormalities*
  • Hematologic Diseases / diagnosis*
  • Hematologic Diseases / genetics*
  • Humans
  • Vestibular Diseases / diagnosis*
  • Vestibular Diseases / genetics*

Supplementary concepts

  • Kabuki syndrome