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Kabuki syndrome, first described in 1967, became a formal diagnosis in 1981. Kabuki syndrome was originally referred to as Kabuki make-up syndrome (KMS). It would also be named (and less commonly referred to as) Niikawa-Kuroki syndrome, after the founding doctors.  Kabuki make-up syndrome would later be shortened to Kabuki syndrome. 

Kabuki syndrome is a rare genetic disorder originally believed to affect approximately 1 in 32,000 births worldwide. Some geneticists believe the occurrence rate may be as high as 1 in 15,000 births, however this data is unconfirmed. The term genetic means an individual is born with a condition and the cause of that condition resides in his or her genetic makeup. Genetic disorders can be passed down (inherited) or spontaneous (de novo).

The first gene recognized to be responsible for Kabuki was discovered in 2010 at the University of Washington. There are currently two genes identified as the cause for Kabuki syndrome. Mutations on KMT2D, formerly known as MLL2, are believed to affect as many as 75% of those diagnosed. Mutations on KDM6A are less common and present in approximately 5% of cases. Studies have shown there are likely additional genes yet to be identified. Kabuki syndrome can be clinically or genetically diagnosed by a Geneticist.

Children and adults affected by Kabuki experience a variety of symptoms, some of which may include: mild to moderate intellectual impairment, growth delays, low muscle tone, feeding difficulties, heart defects, cleft palate, skeletal abnormalities, visual and/or hearing impairments, communication delays, and autistic-like behaviors. Kabuki syndrome affects each individual differently.

Kabuki syndrome does not shorten ones life span, however underlying conditions may.


It is presently known that the KMT2D (formerlly known as MLL2) gene mutation is responsible for approximately 75% of individuals with Kabuki Syndrome.  More recently, mutations of the KDM6A gene have been discovered in approximately 5% of individuals who tested negative for the KMT2D gene mutation. Interestingly, the functions of KDM6A and KMT2D are related to each other.  They function by either adding (in the case of KMT2D ) an activating methyl group or removing (in the case of KDM6A) repressive methyl groups to specific amino acids in a protein called Histone H3. The H3 protein can either be modified by repressive (H3K27me3) or active (H3K4me3) methyl groups.  Since the KMT2D and KDM6A genes have mutations, the KMT2D is not adding the active methyl-groups or KDM6A is not removing the repressive groups.  In essence, although they are doing the opposite activity, the result is the same – repressing the open chromatin state of the H3 protein. As a result, the cells in the body that require gene activation through H3 protein, must  now do without. 

To help families better understand the basics of the discovery please see the following articles on our Resources pages: Understanding the Genetics of Kabuki and Epigenetics and How it Relates to Kabuki Syndrome. It is speculated that Kabuki is a heterogeneous syndrome, meaning that multiple genes could potentially be involved. It is hoped that with continued analysis, other genes will be discovered. 


In 1968 Dr. Yoshikazu Kuroki and colleagues examined a boy in Fukuoka, in the southern part of Japan, with a unique set of malformations that did not fit into known syndromes.  Ten years later another child with similar characteristics was examined in Kanagawa, followed with three others in the ensuing two years. At the same time, in 1967 Dr. Norio Niikawa and colleagues discovered a female infant with an unusual set of characteristics that, again, did not fit into known syndromes. They found four other individuals from Hokkaido, an island north of Japan. In 1981 the combined findings of these individuals were presented as a new malformation syndrome. The name "Kabuki make-up" was selected because of the facial resemblance to the makeup of actors in Kabuki, traditional Japanese theatre. The arched eyebrows, thick eyelashes, eversion of the lateral lower lid, and long palpebral fissures all contributed to this resemblance, especially in children of Asian descent. It has also been referred to as Niikawa-Kuroki syndrome. It is now more commonly known as Kabuki Syndrome.


"The logo is derived from the first Japanese character sign of the word Kabuki syndrome. The first thing you see is the elegant letter K. If you look more closely, you see a person standing with both arms outstretched, which symbolises the invitation to network with one another." - Jos Vergouwen, Netwerk Kabuki Syndroom Netherland

Kabuki Syndrome poster presented at the National Organization for Rare Disorders (NORD) 2022 Summit!

Academic and community collaboration to accelerate Kabuki Syndrome awareness, research and clinical care  

Submitted by Roya Kabuki Program at BCH in collaboration with ATK.        

Abstract Poster Nord 2022.jpg





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