Kabuki syndrome

Reviewed March 2011

What is Kabuki syndrome?

Kabuki syndrome is a disorder that affects many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from a type of traditional Japanese theater called Kabuki in which actors wear makeup that gives them a striking large-eyed facial appearance.

People with Kabuki syndrome have developmental delay and intellectual disability that ranges from mild to severe. They may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have vision problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).

Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and sharply defined pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth.

A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty.

How common is Kabuki syndrome?

Kabuki syndrome occurs in approximately 1 in 32,000 newborns.

What genes are related to Kabuki syndrome?

About 70 percent of cases of Kabuki syndrome are caused by mutations in the KMT2D gene. This gene provides instructions for making a protein that is found in many organs and tissues of the body.

The KMT2D protein functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones, histone methyltransferases control (regulate) the activity of certain genes, which is essential for normal development and function. The histone methyltransferase produced from the KMT2D gene appears to activate certain genes that are important for development.

The KMT2D gene mutations associated with Kabuki syndrome lead to the absence of functional KMT2D protein. A lack of functional KMT2D protein disrupts its role in histone methylation and impairs proper activation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome.

Some people with Kabuki syndrome have no identified KMT2D gene mutation. The cause of the disorder in these individuals is unknown.

Related Gene(s)

Changes in this gene are associated with Kabuki syndrome.

KMT2D

How do people inherit Kabuki syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In a few cases, an affected person is believed to have inherited the mutation from one affected parent.

Where can I find information about diagnosis or management of Kabuki syndrome?

These resources address the diagnosis or management of Kabuki syndrome and may include treatment providers.

Children's Hospital Boston (http://www.childrenshospital.org/az/Site872/mainpageS872P0.html)
Gene Review: Kabuki Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK62111/)
Genetic Testing Registry: Kabuki make-up syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796004)
Kabuki Syndrome Guideline Development Group (UK): Clinical Management Guidelines (http://www.dyscerne.org/dysc/digitalAssets/0/264_Kabuki_Guidelines.pdf)

You might also find information on the diagnosis or management of Kabuki syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/kabuki-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/kabuki-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Kabuki syndrome?

You may find the following resources about Kabuki syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information
Health Topic: Developmental Disabilities (http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html)
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6810/resources/resources/1)
Additional NIH Resources - National Institutes of Health
National Institutes of Health: Kabuki Syndrome Gene Identified (http://www.nih.gov/researchmatters/august2010/08232010kabuki.htm)
Educational resources - Information pages
- Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=273)
- Orphanet (http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=2177)
- Swedish Information Centre for Rare Diseases (http://www.socialstyrelsen.se/rarediseases/kabukisyndrome)
- Victoria (Australia) State Department of Health (http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Kabuki_syndrome?open)
Patient support - For patients and families
- Family Village (http://www.familyvillage.wisc.edu/lib_kabuki.html)
- Kabuki Syndrome Network (http://kabukisyndrome.com/)
- National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/920/viewAbstract)
- University of Kansas Genetics Education Center (http://www.kumc.edu/gec/support/kabuki.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK62111/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Kabuki make-up syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0796004)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Kabuki%20syndrome%22)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Abnormalities,%20Multiple%5BMAJR%5D)%20AND%20(kabuki%20syndrome%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/147920)

What other names do people use for Kabuki syndrome?

Kabuki makeup syndrome
KMS
Niikawa-Kuroki syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Kabuki syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Kabuki syndrome?

autosomal ; autosomal dominant ; cell ; cleft palate ; developmental delay ; DNA ; gene ; histone ; hypotonia ; involuntary ; methyl ; methylation ; methyltransferase ; microcephaly ; molecule ; muscle tone ; mutation ; nystagmus ; otitis media ; palate ; protein ; puberty ; scoliosis ; short stature ; stature ; strabismus ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Armstrong L, Abd El Moneim A, Aleck K, Aughton DJ, Baumann C, Braddock SR, Gillessen-Kaesbach G, Graham JM Jr, Grebe TA, Gripp KW, Hall BD, Hennekam R, Hunter A, Keppler-Noreuil K, Lacombe D, Lin AE, Ming JE, Kokitsu-Nakata NM, Nikkel SM, Philip N, Raas-Rothschild A, Sommer A, Verloes A, Walter C, Wieczorek D, Williams MS, Zackai E, Allanson JE. Further delineation of Kabuki syndrome in 48 well-defined new individuals. Am J Med Genet A. 2005 Jan 30;132A(3):265-72. (http://www.ncbi.nlm.nih.gov/pubmed/15690370?dopt=Abstract)
Kuniba H, Yoshiura K, Kondoh T, Ohashi H, Kurosawa K, Tonoki H, Nagai T, Okamoto N, Kato M, Fukushima Y, Kaname T, Naritomi K, Matsumoto T, Moriuchi H, Kishino T, Kinoshita A, Miyake N, Matsumoto N, Niikawa N. Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome. J Hum Genet. 2009 May;54(5):304-9. doi: 10.1038/jhg.2009.30. Epub 2009 Apr 3. (http://www.ncbi.nlm.nih.gov/pubmed/19343044?dopt=Abstract)
Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010 Sep;42(9):790-3. doi: 10.1038/ng.646. Epub 2010 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/20711175?dopt=Abstract)
Paulussen AD, Stegmann AP, Blok MJ, Tserpelis D, Posma-Velter C, Detisch Y, Smeets EE, Wagemans A, Schrander JJ, van den Boogaard MJ, van der Smagt J, van Haeringen A, Stolte-Dijkstra I, Kerstjens-Frederikse WS, Mancini GM, Wessels MW, Hennekam RC, Vreeburg M, Geraedts J, de Ravel T, Fryns JP, Smeets HJ, Devriendt K, Schrander-Stumpel CT. MLL2 mutation spectrum in 45 patients with Kabuki syndrome. Hum Mutat. 2011 Feb;32(2):E2018-25. doi: 10.1002/humu.21416. Epub 2010 Dec 7. (http://www.ncbi.nlm.nih.gov/pubmed/21280141?dopt=Abstract)
Pottinger CC, Stiff RE, Holroyd JM, Davies SJ. Further evidence of dominant inheritance of Kabuki syndrome. Clin Dysmorphol. 2009 Oct;18(4):215-7. doi: 10.1097/MCD.0b013e32832c012e. (http://www.ncbi.nlm.nih.gov/pubmed/19625956?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.