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

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Abstract

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.

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Funding

This study was supported by the Clinical Research Promotion Project of Shanghai Jiao Tong University (no. JQ201810).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yi-Rou Wang, Jian Wang & Xiu-Min Wang

  2. Department of Genetics, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Jian Wang & Xiu-Min Wang

  3. Huaxi Medical College School of Sichuan University, Sichuan, China

    Nai-Xin Xu

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  1. Yi-Rou Wang
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WYR collected and analyzed data and wrote the manuscript. XNX revised the layout of the manuscript and edited the format. WJ and WXM designed the study and supervised the drafting of the manuscript.

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Correspondence to Xiu-Min Wang.

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Wang, YR., Xu, NX., Wang, J. et al. Kabuki syndrome: review of the clinical features, diagnosis and epigenetic mechanisms. World J Pediatr 15, 528–535 (2019). https://doi.org/10.1007/s12519-019-00309-4

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