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{{Infobox medical condition (new)
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| name
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| caption = A child with kabuki syndrome displaying the “scrunchy face”
| symptoms = Vary widely among patients but may include: Long eyelashes, depressed nasal tip, atypical fingerprints, ear deformity ([[macrotia]] or [[microtia]]), [[hypotonia]], joint hyperflexibility, ptosis, blue [[sclera]], [[cafe au lait spot]], GU anomalies (e.g. [[hypospadias]] or [[horseshoe kidney]]), gi anomalies (e.g. [[anal atresia]] or intestinal malformation), [[hearing loss]], [[immune deficiencies]] (e.g. hypogammaglobinemia), feeding difficulty (infants), [[obesity]] (adulthood), short stature, poor sleep, [[hyperinsulinemia]] ([[hypoglycemia]]), [[epilepsy]], cardiac defects (e.g. [[coarctation of the aorta]]), vertebral anamolies (e.g. [[butterfly vertebrae]]), sparse lateral eyelash, finger anomaly (e.g. short 5th finger), [[cleft palate]], dental issues, [[precocious puberty]], [[scoliosis]], [[hip dysplasia]]
| complications =
| onset = Conception
| duration =
| types = Type 1 (KMT2D), type 2 (KDM6A); other rare mutations unrecognized for now
| causes = Loss-of-function mutations in ''KMT2D'' or ''KDM6A'' genes
| risks =
| diagnosis = Clinical findings; [[genetic testing]]
| differential =
| prevention =
| treatment =
| medication =
| prognosis =
| frequency = 1 in 32,000 births
| deaths =
}}
'''Kabuki syndrome''' (previously known as '''Kabuki-makeup syndrome''' ('''KMS''') or '''Niikawa–Kuroki syndrome''') is a rare [[birth defect|congenital disorder]] of [[genetics|genetic]] origin.<ref>{{Cite news |url=http://www.nih.gov/researchmatters/august2010/08232010kabuki.htm |archive-url=https://web.archive.org/web/20100827123038/http://www.nih.gov/researchmatters/august2010/08232010kabuki.htm |url-status=dead |archive-date=August 27, 2010 |title=Kabuki Syndrome Gene Identified |date=2015-05-20 |work=National Institutes of Health (NIH) |access-date=2017-10-26}}</ref><ref name=":5">{{cite journal |vauthors = 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 |display-authors = 6 |title = Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome |journal = Nature Genetics |volume = 42 |issue = 9 |pages = 790–793 |date = September 2010 |pmid = 20711175 |pmc = 2930028 |doi = 10.1038/ng.646 }}</ref> It affects multiple parts of the body, with varying symptoms and severity, although the most common is the characteristic facial appearance.<ref name=":0">{{cite web |url=https://rarediseases.info.nih.gov/diseases/6810/kabuki-syndrome |title=Kabuki syndrome |work = Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |access-date=2018-04-01}}</ref>
Kabuki syndrome (KS) affects roughly one in 32,000 births.<ref name="GenHomeRef">{{cite web |url=https://medlineplus.gov/genetics/condition/kabuki-syndrome/ |title=Kabuki syndrome |publisher=Genetics Home Reference, U.S. National Library of Medicine |access-date=15 April 2018}}</ref> It was first identified and described in 1981 by two Japanese groups, led by scientists [[Norio Niikawa]] and Yoshikazu Kuroki.<ref name=":1">{{cite journal |vauthors = Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I |title = A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation |journal = The Journal of Pediatrics |volume = 99 |issue = 4 |pages = 570–573 |date = October 1981 |pmid = 7277097 |doi = 10.1016/S0022-3476(81)80256-9 }}</ref> It is named Kabuki syndrome because of the facial resemblance of affected individuals to stage makeup used in ''[[kabuki]]'', a Japanese traditional theatrical form.<ref name="GenHomeRef" />
There are two types of Kabuki syndrome. Type 1 is caused by pathogenic variants in [[KMT2D]] and Type 2 is caused by pathogenic variants in [[UTX (gene)|KDM6A]].
== Signs and symptoms ==
[[File:Kabuki syndrome.jpg|alt=Facial phenotype of en:Kabuki syndrome patient|thumb|Child displaying typical facial phenotype of Kabuki syndrome]]
Specific symptoms for Kabuki syndrome vary, with large differences between affected individuals.<ref name=":0" /> Most people with Kabuki syndrome have distinctive facial features that include arched eyebrows, long eyelashes, elongated eyelids with lower lids that turn out, prominent ears, a flat tip of the nose and a downward slant to the mouth.<ref name=":0" /><ref name="GenHomeRef" />
Overlapping phenotypic features for patients between [[KDM6A]] and [[KMT2D]] variations include prominent ears, abnormal [[dentition]], [[congenital heart disease]], [[feeding difficulties]], [[cryptorchidism]], [[joint hypermobility]], [[Developmental disability|developmental delay]], [[hypotonia]], and behavioral difficulties.
Other common symptoms are skeletal abnormalities, short stature, heart defects, feeding difficulties and a [[failure to thrive]], vision and hearing difficulties, weak muscle tone (hypotonia), small head size ([[microcephaly]]), and frequent infections.<ref name=":0" />
Mild to moderate intellectual disability and mild to severe developmental delay are often associated with Kabuki syndrome.<ref name=":0" /><ref name="GenHomeRef" /><ref>{{cite journal |vauthors = Vaux KK, Jones KL, Jones MC, Schelley S, Hudgins L |title = Developmental outcome in Kabuki syndrome |journal = [[American Journal of Medical Genetics]]. Part A |volume = 132A |issue = 3 |pages = 263–264 |date = January 2005 |pmid = 15523636 |doi = 10.1002/ajmg.a.30338 |s2cid = 32831210 }}</ref> Infants and young children often experience difficulties relating to hypotonia, feeding issues/failure to thrive, infections, surgical repair of heart and palate defects and developmental delays.{{citation needed|date=November 2020}}
Young children with Kabuki syndrome benefit from early intervention services. School age children tend to have fewer medical issues requiring hospitalization, though frequent infections, hearing loss and feeding issues occur. In addition, intellectual impairment, difficulty with visuospatial tasks and maintaining attention usually require an individualized education plan (IEP) if the child attends public school. Older children and adults report difficulties with anxiety. Endocrine abnormalities and immune system abnormalities such as idiopathic [[thrombocytopenia]] (ITP) and [[common variable immune deficiency]] (CVID) are medical issues that tend to present in older children, adolescents and adults.<ref>{{Cite book |vauthors =Adam MP, Hudgins L, Hannibal M |url= https://www.ncbi.nlm.nih.gov/sites/books/NBK62111/ |title=Kabuki Syndrome |date=2019-10-21 |publisher=University of Washington], Seattle |language=en |pmid=21882399}}</ref>
== Causes ==
Type 1 Kabuki syndrome is caused by germline heterozygous loss of function variants in ''[[KMT2D]]'' (formerly known as the ''MLL2''), located on human chromosome 12.<ref name=":5" /> It is estimated that between 55 and 80% of cases of Kabuki syndrome are of Type 1.<ref>{{cite journal | vauthors = Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N, Parker MJ, Crow YJ, Kerr B, Kingston H, Metcalfe K, Chandler K, Magee A, Stewart F, McConnell VP, Donnelly DE, Berland S, Houge G, Morton JE, Oley C, Revencu N, Park SM, Davies SJ, Fry AE, Lynch SA, Gill H, Schweiger S, Lam WW, Tolmie J, Mohammed SN, Hobson E, Smith A, Blyth M, Bennett C, Vasudevan PC, García-Miñaúr S, Henderson A, Goodship J, Wright MJ, Fisher R, Gibbons R, Price SM, C de Silva D, Temple IK, Collins AL, Lachlan K, Elmslie F, McEntagart M, Castle B, Clayton-Smith J, Black GC, Donnai D | display-authors = 6 | title = How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum | journal = European Journal of Human Genetics | volume = 20 | issue = 4 | pages = 381–388 | date = April 2012 | pmid = 22126750 | pmc = 3306863 | doi = 10.1038/ejhg.2011.220 }}</ref><ref name=":6" /><ref name="Adam" /><ref name=":7" /> Type 1 Kabuki syndrome demonstrates an [[autosomal dominant]] pattern of inheritance.
Type 2 Kabuki syndrome is caused by germline hemizygous (in males) or heterozygous (in females) chromosome deletions<ref>{{cite journal | vauthors = Lederer D, Grisart B, Digilio MC, Benoit V, Crespin M, Ghariani SC, Maystadt I, Dallapiccola B, Verellen-Dumoulin C | display-authors = 6 | title = Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome | journal = American Journal of Human Genetics | volume = 90 | issue = 1 | pages = 119–124 | date = January 2012 | pmid = 22197486 | pmc = 3257878 | doi = 10.1016/j.ajhg.2011.11.021 }}</ref> or loss of function point variants<ref>{{cite journal | vauthors = Banka S, Lederer D, Benoit V, Jenkins E, Howard E, Bunstone S, Kerr B, McKee S, Lloyd IC, Shears D, Stewart H, White SM, Savarirayan R, Mancini GM, Beysen D, Cohn RD, Grisart B, Maystadt I, Donnai D | display-authors = 6 | title = Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2) | journal = Clinical Genetics | volume = 87 | issue = 3 | pages = 252–258 | date = March 2015 | pmid = 24527667 | doi = 10.1111/cge.12363 | s2cid = 19578396 }}</ref> involving ''[[UTX (gene)|KDM6A]]'' (formerly known as ''UTX)'', located on the X chromosome. Approximately 5% of cases of Kabuki syndrome are of Type 2. Type 2 Kabuki syndrome demonstrates an [[X-linked dominant]] pattern of inheritance.<ref name=":8">{{cite journal | vauthors = Faundes V, Goh S, Akilapa R, Bezuidenhout H, Bjornsson HT, Bradley L, Brady AF, Brischoux-Boucher E, Brunner H, Bulk S, Canham N, Cody D, Dentici ML, Digilio MC, Elmslie F, Fry AE, Gill H, Hurst J, Johnson D, Julia S, Lachlan K, Lebel RR, Byler M, Gershon E, Lemire E, Gnazzo M, Lepri FR, Marchese A, McEntagart M, McGaughran J, Mizuno S, Okamoto N, Rieubland C, Rodgers J, Sasaki E, Scalais E, Scurr I, Suri M, van der Burgt I, Matsumoto N, Miyake N, Benoit V, Lederer D, Banka S | display-authors = 6 | title = Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2 | journal = Genetics in Medicine | volume = 23 | issue = 7 | pages = 1202–1210 | date = July 2021 | pmid = 33674768 | pmc = 8257478 | doi = 10.1038/s41436-021-01119-8 }}</ref>
Most cases of Kabuki syndrome occur [[De novo mutation|''de novo'']]. That is, the mutation did not come from the parents and the gene was mutated early in [[Prenatal development|embryological development]]. However, several cases of inherited mutations causing Type 1 or Type 2 Kabuki syndrome are now known.<ref name="Adam" /><ref name=":8" />
Some cases of Kabuki syndrome have no identifiable causative mutation.<ref name="GenHomeRef" /> These may be caused by types of mutations that are difficult to detect via current routine investigations. Another possibility is that these patients have other disorders that share some features with Kabuki syndrome.
== Pathophysiology ==
The ''KMT2D'' and ''KDM6A'' genes belong to a family of genes called [[Chromatin remodeling|chromatin-modifying]] [[enzyme]]s. Specifically, these genes code for a [[histone methyltransferase]] (KMT2D) and a [[Demethylase|histone demethylase]] (KDM6A), and play a part in the regulation of [[gene expression]].<ref name=":2">{{cite journal | title = Kabuki Syndrome | journal = GeneReviews [Internet] | date = 16 May 2013 | pmid = 21882399 | url = https://www.ncbi.nlm.nih.gov/books/NBK62111/ | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A | last1 = Adam | first1 = M. P. | last2 = Everman | first2 = D. B. | last3 = Mirzaa | first3 = G. M. | last4 = Pagon | first4 = R. A. | last5 = Wallace | first5 = S. E. | author6 = Bean LJH | last7 = Gripp | first7 = K. W. | last8 = Amemiya | first8 = A. | last9 = Adam | first9 = M. P. | last10 = Hudgins | first10 = L. | last11 = Hannibal | first11 = M. }}</ref> Under normal circumstances, these enzymes transfer methyl groups on and off histones to regulate genes via [[epigenetic]] pathways. When the genes that encode these enzymes are mutated, epigenetic activation of certain developmental genes is impaired and developmental abnormalities occur, leading to the characteristics of Kabuki syndrome patients.<ref name=":2" /> The specific developmental genes that are affected by the impaired epigenetic mechanisms in Kabuki syndrome are not yet fully known.<ref name=":2" />
There are hundreds of different mutations that have been identified in Kabuki syndrome patients. Most of these mutations are in the ''KMT2D'' gene and involve a change in amino acid sequence that creates a shortened and nonfunctional chromatin-modifying enzyme.<ref name=":7">{{cite journal | vauthors = Bögershausen N, Wollnik B | title = Unmasking Kabuki syndrome | journal = Clinical Genetics | volume = 83 | issue = 3 | pages = 201–211 | date = March 2013 | pmid = 23131014 | doi = 10.1111/cge.12051 | s2cid = 204999137 }}</ref>
==Diagnosis==
[[File:Kabuki Syndrome 6.jpg|thumb|Individual with Kabuki Syndrome from infancy to adulthood]]
Kabuki syndrome is diagnosed with [[genetic testing]] (targeted, whole [[Exome sequencing|exome]] or [[whole genome sequencing]]).<ref name=":0" /> When genetic testing is not available, Kabuki syndrome is diagnosed clinically (through identifying symptoms, physical exams, and lab results), most commonly by a geneticist.
A consensus on clinical diagnostic criteria for KS was defined in December 2018 by an international group of experts.<ref name="Adam">{{cite journal |vauthors = Adam MP, Banka S, Bjornsson HT, Bodamer O, Chudley AE, Harris J, Kawame H, Lanpher BC, Lindsley AW, Merla G, Miyake N, Okamoto N, Stumpel CT, Niikawa N |display-authors = 6 |title = Kabuki syndrome: international consensus diagnostic criteria |journal = Journal of Medical Genetics |volume = 56 |issue = 2 |pages = 89–95 |date = February 2019 |pmid = 30514738 |doi = 10.1136/jmedgenet-2018-105625 |s2cid = 54484060 |hdl = 2336/620938 |hdl-access = free }}</ref> The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria:
# a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness;
# short columella with depressed nasal tip;
# large, prominent or cupped ears; and # persistent fingertip pads.
Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, were included in the publication.<ref name="Adam" />
The original description of Kabuki syndrome by Niikawa et al.<ref name=":3" /> defined five cardinal manifestations, although some of these “cardinal manifestations” may or may not be present in a patient with Kabuki syndrome.
# Typical facial features: Elongated palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows with the lateral third displaying sparseness or notching; short columella with depressed nasal tip; large, prominent, or cupped ears<ref name=":3" /><ref>{{cite journal |vauthors = Wilson GN |title = Thirteen cases of Niikawa-Kuroki syndrome: report and review with emphasis on medical complications and preventive management |journal = American Journal of Medical Genetics |volume = 79 |issue = 2 |pages = 112–120 |date = September 1998 |pmid = 9741469 |doi = 10.1002/(SICI)1096-8628(19980901)79:2<112::AID-AJMG7>3.0.CO;2-S }}</ref><ref name=":6">{{cite journal |vauthors = Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ |display-authors = 6 |title = Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome |journal = American Journal of Medical Genetics. Part A |volume = 155A |issue = 7 |pages = 1511–1516 |date = July 2011 |pmid = 21671394 |pmc = 3121928 |doi = 10.1002/ajmg.a.34074 }}</ref><ref name="Kabuki syndrome: Clinical data in 2">{{cite journal |vauthors = Schrander-Stumpel CT, Spruyt L, Curfs LM, Defloor T, Schrander JJ |title = Kabuki syndrome: Clinical data in 20 patients, literature review, and further guidelines for preventive management |journal = American Journal of Medical Genetics. Part A |volume = 132A |issue = 3 |pages = 234–243 |date = January 2005 |pmid = 15690368 |doi = 10.1002/ajmg.a.30331 |s2cid = 42186309 }}</ref><ref>{{cite journal |vauthors = Armstrong L, Abd El Moneim A, Aleck K, Aughton DJ, Baumann C, Braddock SR, Gillessen-Kaesbach G, Graham JM, 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 |display-authors = 6 |title = Further delineation of Kabuki syndrome in 48 well-defined new individuals |journal = American Journal of Medical Genetics. Part A |volume = 132A |issue = 3 |pages = 265–272 |date = January 2005 |pmid = 15690370 |doi = 10.1002/ajmg.a.30340 |s2cid = 27626946 }}</ref>
# Skeletal anomalies: Spinal column abnormalities, including sagittal cleft vertebrae, butterfly vertebrae, narrow intervertebral disc space, and/or scoliosis, [[Brachydactyly]] V Brachymesophalangy [[Clinodactyly]] of fifth digits
# Dermatoglyphic abnormalities: persistence of fetal fingertip pads
# Mild to moderate intellectual disability
# Postnatal growth deficiency
Diagnosis can be difficult given the large spectrum of disease. The fact that some patients do not carry one of the two known mutations or can carry multiple mutations complicates the diagnosis further. In 2017, researchers published work that showed people with Kabuki syndrome have a unique pattern of [[DNA methylation]].<ref>{{Cite journal |last1=Aref-Eshghi |first1=Erfan |last2=Schenkel |first2=Laila C. |last3=Lin |first3=Hanxin |last4=Skinner |first4=Cindy |last5=Ainsworth |first5=Peter |last6=Paré |first6=Guillaume |last7=Rodenhiser |first7=David |last8=Schwartz |first8=Charles |last9=Sadikovic |first9=Bekim |date=2017-11-02 |title=The defining DNA methylation signature of Kabuki syndrome enables functional assessment of genetic variants of unknown clinical significance |journal=Epigenetics |language=en |volume=12 |issue=11 |pages=923–933 |doi=10.1080/15592294.2017.1381807 |issn=1559-2294 |pmc=5788422 |pmid=28933623}}</ref> This unique methylation pattern may lead to new ways to diagnose Kabuki syndrome in those who do not show mutations in [[KMT2D]] or [[UTX (gene)|KDM6A]], but still present with a Kabuki syndrome [[phenotype]].
== Screening ==
Due to its rarity, Kabuki syndrome is not screened for in routine [[prenatal testing]] including [[blood test]]s, [[chorionic villus sampling]] (CVS), or [[amniocentesis]]. Although not routine for the general population, if Kabuki syndrome is a specific concern (i.e. expectant mother who has been diagnosed with Kabuki syndrome or sibling with KS), it is possible to test for one of the specific mutations.<ref name="GenHomeRef" /> This prenatal testing does require a CVS or amniocentesis. However Kabuki syndrome is usually not inherited and therefore most cases do not have a positive family history.<ref name=":0" /><ref name="GenHomeRef" /> Kabuki syndrome can have positive screening tests, such as [[cystic hygroma]] seen on [[Nuchal scan|nuchal translucency ultrasound screening]], although these findings are non-specific and have a wide [[differential diagnosis]].<ref>{{cite journal | vauthors = Long A, Sinkovskaya ES, Edmondson AC, Zackai E, Schrier Vergano SA | title = Kabuki syndrome as a cause of non-immune fetal hydrops/ascites | journal = American Journal of Medical Genetics. Part A | volume = 170 | issue = 12 | pages = 3333–3337 | date = December 2016 | pmid = 27568880 | doi = 10.1002/ajmg.a.37956 | s2cid = 26914645 }}</ref><ref>{{cite journal | vauthors = Lajeunesse C, Stadler A, Trombert B, Varlet MN, Patural H, Prieur F, Chêne G | title = [First-trimester cystic hygroma: prenatal diagnosis and fetal outcome] | journal = Journal de Gynécologie, Obstétrique et Biologie de la Reproduction | volume = 43 | issue = 6 | pages = 455–462 | date = June 2014 | pmid = 23747217 | doi = 10.1016/j.jgyn.2013.04.005 }}</ref>
==Management==
Management is supportive, aimed at improving quality of life.<ref>{{Citation |last1=Adam |first1=Margaret P. |title=Kabuki Syndrome |date=1993 |work=GeneReviews® |editor-last=Adam |editor-first=Margaret P. |url=https://www.ncbi.nlm.nih.gov/books/NBK62111/ |access-date=2024-02-01 |place=Seattle (WA) |publisher=University of Washington, Seattle |pmid=21882399 |last2=Hudgins |first2=Louanne |last3=Hannibal |first3=Mark |editor2-last=Feldman |editor2-first=Jerry |editor3-last=Mirzaa |editor3-first=Ghayda M. |editor4-last=Pagon |editor4-first=Roberta A.}}</ref> Newly diagnosed patients with Kabuki syndrome will often undergo tests that are aimed at detecting common abnormalities associated with the syndrome. They include an [[echocardiogram]] (ultrasound of the heart) for detection of structural heart defects, kidney ultrasound for detection of structural renal abnormalities, [[immunoglobulin]] levels, pneumococcal titers and a hearing screening test. Further evaluation and testing by specialists may be indicated in addition to cardiology, nephrology, allergy/immunology, audiology-mentioned above. This may include orthopedics (such as hip dysplasia), pulmonary (sleep study to rule out obstructive sleep apnea due to hypotonia), ophthalmology evaluation (vision screen), ENT evaluation (hearing evaluation), Neurology evaluation (i.e. if seizures present), Hematology evaluation (if bleeding disorder), GI evaluation (if gi abnormalities), or others as needed.
There are currently no Kabuki syndrome specific treatments and there is no cure. Treatment plans are customized to address the symptoms the individual is experiencing.<ref name=":2" /> For example, someone experiencing seizures will be treated with the standard anti-epilepsy therapies.<ref name=":2" /> Additionally, patients with Kabuki syndrome are routinely evaluated and monitored to address problems that may develop, such as vision or hearing problems, or cognitive difficulties.<ref name=":2" /> If congenital heart disease is present, prophylactic antibiotics may be recommended before any procedures such as dental work that might cause infection.<ref name=":2" />
== Prognosis ==
Life expectancy is not shortened in most cases of Kabuki syndrome. Some patients have coexisting conditions which may shorten life expectancy, such as hypoplastic left heart syndrome or kidney dysfunction. It is important that patients with cardiac, renal, or immunologic issues are identified and well-managed.<ref name=":0" />
== Epidemiology ==
Kabuki syndrome occurs about once in every 32,000 births.<ref name="GenHomeRef" /><ref name=":3">{{cite journal | vauthors = Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T | title = Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency | journal = The Journal of Pediatrics | volume = 99 | issue = 4 | pages = 565–569 | date = October 1981 | pmid = 7277096 | doi = 10.1016/S0022-3476(81)80255-7 }}</ref> The disease appears to affect all population groups equally, with no differences based on sex, race, or environment.<ref>{{Cite news|url=https://rarediseases.org/rare-diseases/kabuki-syndrome/|title=Kabuki Syndrome - NORD (National Organization for Rare Disorders)|work=NORD (National Organization for Rare Disorders)|access-date=2018-04-20 }}</ref> In 2023, a project called Kabuki Count was launched by a global collection of patient advocacy groups (led by the Kabuki Syndrome Foundation) as a global census to document how many people have Kabuki syndrome worldwide.
== Research ==
Research on Kabuki syndrome is limited due to its low [[Incidence (epidemiology)|incidence]].<ref name="GenHomeRef" /> Despite this, several groups around the world are studying Kabuki syndrome.
In the United States, these include Dr. Hans Bjornson at [[Johns Hopkins School of Medicine|Johns Hopkins University]], The Roya Kabuki Program at [[Boston Children's Hospital]], Dr. Mark Hannibal at the [[Michigan Medicine|University of Michigan]], Dr. Margaret Adam at [[Seattle Children's|Seattle Children's Hospital]], Dr. Jacqui Harris at [[Kennedy Krieger Institute]], as well as groups at University of Colorado, University of Utah, University of South Florida and others.<ref>{{Cite web|url=http://www.childrenshospital.org/conditions-and-treatments/conditions/k/kabuki-syndrome|title=Kabuki Syndrome {{!}} Boston Children's Hospital|website=www.childrenshospital.org |access-date=2018-04-24}}</ref><ref>{{Citation| author =Johns Hopkins Medicine|title=#TomorrowsDiscoveries: Intellectual Disability Treatments — Dr. Hans Bjornsson|date=2015-10-07|url=https://www.youtube.com/watch?v=BVLSJvYYaGA |archive-url=https://ghostarchive.org/varchive/youtube/20211221/BVLSJvYYaGA |archive-date=2021-12-21 |url-status=live|access-date=2018-04-24}}{{cbignore}}</ref>
In the UK, Prof Siddharth Banka's group at the [[University of Manchester]] and Manchester University Hospitals has a research program for Kabuki syndrome. In Canada, Dr. Rosanna Weksberg at [[SickKids]] and [[University of Toronto]]. Several European groups based in Italy, France, Germany and the Netherlands are also actively working on improving understanding of the condition and to identifying potential treatments.
In 2018, the Kabuki Syndrome Foundation was established to accelerate research efforts to treat or cure Kabuki syndrome. They launched the Kabuki Syndrome Outcome measures and Biomarkers Consortium (KSOC) in 2023 which is a collaborative clinical research study of Kabuki syndrome biomarkers.
== History ==
In 1969, [[Norio Niikawa]] MD, a geneticist in Japan, was treating a child patient presenting with unique facial characteristics and various health problems. Never having seen this constellation of symptoms before, Dr Niikawa wondered if he was faced with an undiagnosed condition, a disorder with a genetic basis. Over the next several years, this physician treated several other patients with the same symptoms in his outpatient genetics clinic, furthering support for a disorder never before diagnosed.<ref name=":4">{{cite journal | vauthors = Matsumoto N, Niikawa N | title = Kabuki make-up syndrome: a review | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 117C | issue = 1 | pages = 57–65 | date = February 2003 | pmid = 12561059 | doi = 10.1002/ajmg.c.10020 | s2cid = 39599820 }}</ref>
In 1979, Dr Niikawa presented his findings and hypothesis at the first Japan [[Teratology|Dysmorphology]] Conference. A fellow physician at this conference, Yoshikazu Kuroki, recognized the symptoms, and realized that he had also seen several paediatric patients with this presentation; he presented two of his own cases at the second annual conference the following year. In 1981, the two doctors separately submitted articles on this new diagnosis to the ''Journal of Pediatrics''.<ref name=":1" /><ref name=":4" /><ref>{{cite journal | vauthors = Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T | title = Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency | journal = The Journal of Pediatrics | volume = 99 | issue = 4 | pages = 565–569 | date = October 1981 | pmid = 7277096 | doi = 10.1016/s0022-3476(81)80255-7 }}</ref>
Dr Niikawa coined the term 'Kabuki syndrome' (also known as Kabuki make-up syndrome or Niikawa–Kuroki syndrome) as a reference to traditional Japanese theatre which he respected greatly. Many of the children presenting with this diagnosis had unusual, elongated lower eyelids, and this feature was reminiscent of the theatrical make-up worn by actors in [[Kabuki]] theatre.<ref name="Kabuki syndrome: Clinical data in 2"/><ref>{{cite journal | vauthors = Kasdon BD, Fox JE | title = Kabuki syndrome: diagnostic and treatment considerations | journal = Mental Health in Family Medicine | volume = 9 | issue = 3 | pages = 171–179 | date = September 2012 | pmid = 23997823 | pmc = 3622909 }}</ref>
As reported by Dr. Niikawa "The name, 'Kabuki make-up', of the syndrome was given by myself, because the facial appearance of patients, especially eversion of their lower eyelids, is reminiscent of the makeup of actors in Kabuki, the traditional form of Japanese theater. Kabuki was founded early in the 17th century in Japan and over the next 300 years developed into a sophisticated form of theater. Kabuki actors usually apply traditional makeup to strengthen their eyes, especially in a hero play, and they are very proud of their performing art."<ref>{{Cite web|url=http://istituti.unicatt.it/genetica-medica-Niikawa_Kabuki.pdf|title=Niikawa Presentation}}</ref>
The individual [[kanji]], from left to right, mean ''sing'' (歌), ''dance'' (舞), and ''skill'' (伎). Kabuki is therefore sometimes translated as "the art of singing and dancing".
The genes for Kabuki syndrome were discovered in 2010 and 2012 for Type 1 and Type 2 Kabuki syndrome respectively.<ref>{{Cite journal |last1=Ng |first1=Sarah B |last2=Bigham |first2=Abigail W |last3=Buckingham |first3=Kati J |last4=Hannibal |first4=Mark C |last5=McMillin |first5=Margaret J |last6=Gildersleeve |first6=Heidi I |last7=Beck |first7=Anita E |last8=Tabor |first8=Holly K |last9=Cooper |first9=Gregory M |last10=Mefford |first10=Heather C |last11=Lee |first11=Choli |last12=Turner |first12=Emily H |last13=Smith |first13=Joshua D |last14=Rieder |first14=Mark J |last15=Yoshiura |first15=Koh-ichiro |date=September 2010 |title=Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome |journal=Nature Genetics |language=en |volume=42 |issue=9 |pages=790–793 |doi=10.1038/ng.646 |pmid=20711175 |issn=1061-4036|pmc=2930028 }}</ref>
== In popular culture ==
* ''[[The Good Doctor (American TV series)|The Good Doctor]]'' is an American medical drama television series that airs on [[American Broadcasting Company|ABC]]. Season five's ninth episode features Matthew Horner, an actor with Kabuki syndrome.<ref>{{Cite web | first=Brittney|last= Verner |date=2022-03-07 |title=Local doctor and patient featured on ABC's The Good Doctor |url=https://www.wmar2news.com/news/local-news/local-doctor-and-patient-featured-on-abcs-the-good-doctor |access-date=2023-05-27 |website=WMAR 2 News Baltimore |language=en}}</ref>
* ''Nineteen Paper Cranes'' is a short documentary by [[Michael Joseph McDonald]]. The film follows a [[Deafness|deaf]] Japanese papermaker with Kabuki syndrome as she memorializes the nineteen victims of the [[Sagamihara stabbings]].<ref>{{Cite web |title=19 Paper Cranes – Global Justice Film Festival |url=http://globaljusticefilmfestival.ca/films/detail/19-paper-cranes |access-date=2023-05-27 |website=globaljusticefilmfestival.ca |language=en}}</ref>
== References ==
{{Reflist}}
== External links ==
{| class="wikitable"
|+
!
!Website
|-
|Patient Advocacy
|[http://www.allthingskabuki.org All Things Kabuki]
|-
|
|[https://www.kabukiuk.org.uk/ Kabuki UK]
|-
|
|[https://sakks.org Supporting Aussie Kids with Kabuki Syndrome (SAKKS)]
|-
|
|[https://www.syndromekabuki.fr Association Syndrome Kabuki]
|-
|Research
|[https://www.kabukisyndromefoundation.org Kabuki Syndrome Foundation]
|-
|
|[http://royakabuki.org Roya Kabuki Program]
|-
|Conferences/Gatherings
|[https://thekabukigathering.org Texas Kabuki Gathering]
|}
{{Medical resources
| DiseasesDB=32161
| ICD10={{ICD10|Q|87|0|q|87}}
| ICD9={{ICD9|759.89}}
| ICDO=
| OMIM=147920
| MedlinePlus=
| eMedicineSubj=
| eMedicineTopic=
| MeshID=C537705
| GARDNum = 6810
| GARDName = kabuki-syndrome
| GeneReviewsName=Kabuki Syndrome
| GeneReviewsNBK=NBK62111
| Orphanet = 2322
}}
{{commons category}}
{{Transcription factor/coregulator deficiencies}}
[[Category:Rare syndromes]]
[[Category:Syndromes affecting the heart]]
[[Category:Genodermatoses]]
[[Category:Syndromes affecting hearing]]
[[Category:Syndromes with craniofacial abnormalities]]
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