Rare Cardiology News

Disease Profile

Kabuki syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NKS; Niikawa-Kuroki syndrome; KMS;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Ear, Nose, and Throat Diseases;

Summary

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]

Symptoms

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]

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.

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
Broad, arched eyebrows
High-arched eyebrows
High, rounded eyebrows
Arched eyebrows
Thick, flared eyebrows

[ more ]

0002553
Long eyelashes
Increased length of eyelashes
Unusually long eyelashes

[ more ]

0000527
Macrotia
Large ears
0000400
Protruding ear
Prominent ears
Prominent ear

[ more ]

0000411
Short 5th finger
Short fifth finger
Short pinky finger
Short pinkie finger
Short little finger
Short fifth fingers

[ 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 the aorta
Narrowing of 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
Decreased circumference of cranium
Abnormally small skull
Small head circumference
Reduced head circumference
Decreased size of skull

[ more ]

0000252
Microdontia
Decreased width of tooth
0000691
Muscular hypotonia
Low or weak muscle tone
0001252
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
Small stature
Decreased body height

[ more ]

0004322
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
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

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Cause

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]

Diagnosis

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.

    Treatment

    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.

      Organizations

      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

        Learn more

        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

        • MedlinePlus Genetics 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.

            References

            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; https://ghr.nlm.nih.gov/condition/kabuki-syndrome.
            3. Margaret Adam. Kabuki syndrome. Orphanet. April, 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2322.
            4. Marla J. F. O'Neill. Kabuki Syndrome. OMIM. 2016; https://www.ncbi.nlm.nih.gov/omim/147920.
            5. Adam MP, Hudgins L.. Kabuki syndrome: a review. Clinical Genetics. 2005; 67(3):209-219.

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