National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Kabuki syndrome

Kabuki syndrome is a rare disorder that affects multiple parts of the body. It is present from birth. Specific symptoms and severity can vary. Features often include a characteristic facial appearance; skeletal abnormalities; short stature; heart defects; and intellectual disability.[1][2] Other signs and symptoms may include seizures, microcephaly, weak muscle tone (hypotonia), eye problems, cleft palate, and dental problems.[2] A variety of other health problems may also occur. Kabuki syndrome is most often caused by a mutation in the KMT2D gene, and inherited in an autosomal dominant manner. Some cases are due to a mutation in the KDM6A gene and are inherited in an X-linked dominant manner.[1] Treatment is focused on the specific signs and symptoms in each affected person.[3]
Last updated: 2/8/2016
Kabuki syndrome is present from birth (it is congenital). People with Kabuki syndrome have similar, characteristic facial features. These include arched eyebrows; wide eyes that often slant upwards; long and thick eyelashes; a blue tint to the whites of the eyes (blue sclerae); prominent ears; downward slanting corners of the mouth; and a depressed tip of the nose. People with Kabuki syndrome may also have cleft lip; a highly arched or cleft palate; and widely spaced, irregular teeth.[4][3]

Most people with Kabuki syndrome have mild to moderate intellectual disability, although this varies considerably. Early speech and language delay is common and some language-related difficulties usually persist.[5]

Other medical problems may also be present. Congenital heart defects are common. Skeletal abnormalities may include a short and curved pinky finger (clinodactyly); spine abnormalities; and joint dislocations. Affected people often have weak muscle tone (hypotonia); feeding difficulties; seizures; and a small head size (microcephaly). Vision and hearing problems may also be present. Some affected children are more susceptible to infections, particularly ear infections.[3]
Last updated: 2/8/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 110 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal dermatoglyphics
Abnormal fingerprints
0007477
Butterfly vertebrae 0003316
Eversion of lateral third of lower eyelids 0007655
Hemivertebrae
Missing part of vertebrae
0002937
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
Thick, flared eyebrows
High-arched eyebrows
[ more ] 		0002553
Long eyelashes
Increased length of eyelashes
Unusually long eyelashes
[ more ] 		0000527
Macrotia
Large ears
0000400
Protruding ear
Prominent ear
Prominent ears
[ more ] 		0000411
Short 5th finger
Short fifth finger
Short fifth fingers
Short little finger
Short pinkie finger
Short pinky finger
[ more ] 		0009237
Short columella 0002000
Short middle phalanx of finger
Short middle bone of finger
0005819
Sparse lateral eyebrow
Limited hair on end of eyebrow
0005338
30%-79% of people have these symptoms
Abnormal cardiac septum morphology 0001671
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Cleft palate
Cleft roof of mouth
0000175
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta
[ more ] 		0001680
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypodontia
Failure of development of between one and six teeth
0000668
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Microdontia
Decreased width of tooth
0000691
Ptosis
Drooping upper eyelid
0000508
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection
[ more ] 		0002719
Scoliosis 0002650
Sensorineural hearing impairment 0000407
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Ventriculomegaly 0002119
Widely spaced teeth
Wide-spaced teeth
Widely-spaced teeth
[ more ] 		0000687
5%-29% of people have these symptoms
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Atrioventricular canal defect 0006695
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Brachydactyly
Short fingers or toes
0001156
Coloboma
Notched pupil
0000589
Congenital diaphragmatic hernia 0000776
Crossed fused renal ectopia 0004736
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Cupped ear
Cup-shaped ears
Simple, cup-shaped ears
[ more ] 		0000378
Duplicated collecting system 0000081
EEG abnormality 0002353
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ] 		0002827
Hydronephrosis 0000126
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias 0000047
Lip pit 0100267
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance
[ more ] 		0000298
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Natal tooth
Born with teeth
Teeth present at birth
[ more ] 		0000695
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Preauricular skin tag 0000384
Precocious puberty
Early onset of puberty
Early puberty
[ more ] 		0000826
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney
[ more ] 		0008678
Seizure 0001250
Small hand
Disproportionately small hands
0200055
Ureteropelvic junction obstruction 0000074
1%-4% of people have these symptoms
Areolar fullness 0032315
Depressed nasal tip
Caved in nasal tip
Depressed tip of nose
Flat nasal tip
Flat tip of nose
Flattened nasal tip
Nasal tip, depressed
[ more ] 		0000437
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Global developmental delay 0001263
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hirsutism
Excessive hairiness
0001007
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness
[ more ] 		0001388
Long palpebral fissure
Broad opening between the eyelids
Long opening between the eyelids
Wide opening between the eyelids
[ more ] 		0000637
Lower lip pit 0000196
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Neonatal hypoglycemia
Low blood sugar in newborn
0001998
Postnatal growth retardation
Growth delay as children
0008897
Prominent fingertip pads
Prominent finger pads
0001212
Recurrent otitis media
Recurrent middle ear infection
0000403
Percent of people who have these symptoms is not available through HPO
Abnormal vertebral morphology 0003468
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality
[ more ] 		0000164
Anal atresia
Absent anus
0002023
Anal stenosis
Narrowing of anal opening
0002025
Anoperineal fistula 0005218
Autoimmune thrombocytopenia 0001973
Autosomal dominant inheritance 0000006
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose
[ more ] 		0000455
Cafe-au-lait spot 0000957
Central hypotonia 0011398
Congenital hip dislocation
Dislocated hip since birth
0001374
Congenital hypothyroidism
Underactive thyroid gland from birth
0000851
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile
[ more ] 		0004325
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ] 		0000689
Feeding difficulties in infancy 0008872
Hemolytic anemia 0001878
Intestinal malrotation 0002566
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints
[ more ] 		0001382
Malabsorption
Intestinal malabsorption
0002024
Micropenis
Short penis
Small penis
[ more ] 		0000054
Muscular hypotonia
Low or weak muscle tone
0001252
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Preauricular pit
Pit in front of the ear
0004467
Premature thelarche
Premature breast development
0010314
Prominent eyelashes 0011231
Recurrent aspiration pneumonia 0002100
Sparse and thin eyebrow
Thin, sparse eyebrows
0000535
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
X-linked dominant inheritance 0001423
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Last updated: 7/1/2020
Kabuki syndrome is a genetic condition that may be caused by a mutation in the KMT2D gene (in up to 80% of cases) or the KDM6A gene. In some people with Kabuki syndrome, the cause is unknown.

The KMT2D gene gives the body instructions to make an enzyme called lysine-specific methyltransferase 2D, which is present in many parts of the body. This enzyme modifies proteins called histones, which attach to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), the enzyme helps to control the activity of certain genes. It appears to activate certain genes that are important for development.

The KDM6A gene gives the body instructions to make an enzyme called lysine-specific demethylase 6A. This enzyme helps to remove methyl groups from certain histones. Like lysine-specific methyltransferase 2D, this enzyme also helps to control the activity of certain genes. Research suggests that the two enzymes work together.

Mutations in either of these genes result in the absence of the related enzyme, which disrupts histone methylation and impairs the activation of certain genes needed for normal development.[2]
Last updated: 2/8/2016
Kabuki syndrome is most often caused by a change (mutation) in the KMT2D gene, which is inherited in an autosomal dominant manner.[2] This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of the condition. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Some cases are caused by mutations in the KDM6A gene, inherited in an X-linked dominant manner.[2] This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition.

Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females.

If a father has the mutated X-linked gene:
  • all of his daughters will inherit the mutated gene (they will all receive his X chromosome)
  • none of his sons will inherit the mutated gene (they only inherit his Y chromosome)
If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene.

Most cases of Kabuki syndrome are not inherited from a parent and result from a new mutation in one of these genes (in people with no family history of Kabuki syndrome). In a few cases an affected person is believed to have inherited the mutation from an affected parent.[2] In either case, a person with a disease-causing mutation may still pass it on to his/her offspring.
Last updated: 2/9/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
Information about the long-term outlook (prognosis) for people with Kabuki syndrome is limited. It is thought that the prognosis for living into adulthood is good, particularly if congenital anomalies (such as congenital heart defects), and infections, are properly managed in childhood.[5] Life expectancy is somewhat dependent on cardiac (heart) and immunologic complications.[3]
Last updated: 2/8/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis of KS includes CHARGE, branchiootorenal, Ehlers-Danlos (hypermobile form), Hardikar syndromes, IRF6-related disorders and 22q11 deletion syndrome (see these terms). Various chromosomal anomalies can also induce clinical signs that overlap the KS clinical spectrum.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Kabuki syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Kabuki syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Kabuki syndrome:
    International registry for Kabuki syndrome
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Kabuki syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    Kabuki syndrome 1
    Kabuki syndrome 2
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Kabuki syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I have a friend who has Kabuki make up syndrome and she wants to know will she be able to have children? See answer


  1. Lederer D, Shears D, Benoit V, Verellen-Dumoulin C, Maystadt I. A three generation X-linked family with Kabuki syndrome phenotype and a frameshift mutation in KDM6A. Am J Med Genet A. May, 2014; 164A(5):1289-1292.
  2. Kabuki syndrome. Genetics Home Reference. October, 2013; http://ghr.nlm.nih.gov/condition/kabuki-syndrome.
  3. Margaret Adam. Kabuki syndrome. Orphanet. April, 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2322.
  4. Marla J. F. O'Neill. Kabuki Syndrome. OMIM. 2016; http://www.ncbi.nlm.nih.gov/omim/147920.
  5. Adam MP, Hudgins L.. Kabuki syndrome: a review. Clinical Genetics. 2005; 67(3):209-219.