|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|
|Types||type 1 (KMT2D), type 2 (KDM6A); other rare mutations unrecognized for now|
|Causes||loss-of-function mutations in KMT2D or KDM6A genes|
|Diagnostic method||clinical findings; genetic testing|
|Frequency||1 in 32,000 births|
Kabuki syndrome (also previously known as kabuki makeup syndrome, KMS, or Niikawa-Kuroki Syndrome) is a pediatric congenital disorder of genetic origin. It affects multiple parts of the body with varying symptoms and severity, although the most common is the characteristic facial appearance. It is quite rare, affecting roughly one in 32,000 births. It was first identified and described in 1981 by two Japanese groups, led by scientists Norio Niikawa and Yoshikazu Kuroki. It is named Kabuki syndrome because of the facial resemblance of affected individuals to stage makeup used in kabuki, a Japanese traditional theatrical form.
Signs and symptoms
Specific symptoms for Kabuki syndrome vary, with large differences between affected individuals. 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.
Other common symptoms are skeletal abnormalities, heart defects, feeding difficulties and a failure to thrive, vision and hearing difficulties, weak muscle tone (hypotonia), small head size (microencephaly), and frequent infections. Mild to moderate intellectual disability and mild to severe developmental delay are often associated with Kabuki syndrome.
Most cases of Kabuki syndrome are caused by loss-of-function mutations in two different genes: KMT2D and KDM6A. However, about 30% of cases have no mutations that could be identified in either gene where the cause is still unknown.
It is estimated that between 55-80% of cases of Kabuki syndrome are caused by mutations in the KMT2D gene, formerly known as the MLL2 gene. This gene is located on chromosome 12 and is one of the genes involved in the development of this disorder. A mutation in the KMT2D gene results in a loss of function for the protein this gene codes for, which is a lysine (K)-specific methyltransferase 2D enzyme.
Another 2-6% of cases are related to mutations in the KDM6A gene. This mutation produces a nonfunctional lysine (K)-specific demethylase 6A. This gene is located on the X chromosome.
Kabuki syndrome can be inherited or caused by a new mutation (called a de novo mutation). Inherited mutations to the KMT2D gene are inherited in an autosomal dominant pattern while those to the KDM6A gene are inherited in an X-linked dominant pattern. The vast majority of mutations occur de novo.  That is, the parents are unaffected and the gene was mutated early in embryological development.
This section needs expansion. You can help by adding to it. (April 2018)
Hundreds of mutations have been identified in diagnosed kabuki syndrome patients for these genes. Most of these mutations involve a change in amino acid sequence that codes for a premature stop codon, and therefore nonfunctional, short enzymes.[medical citation needed] These two genes belong to a family of genes called chromatin-modifying enzymes. Specifically these genes code for a histone methyltransferase (KMT2D) and a histone demethylase (KDM6A), and play a part in the regulation of gene expression.[medical citation needed]
These enzymes transfer methyl groups on and off histones to regulate genes via epigenetic pathways. Epigenetic activation of certain developmental genes is impaired by loss of either enzyme and developmental abnormalities occur, leading to the characteristics of kabuki syndrome patients. The specific developmental genes have not been fully identified.[medical citation needed]
Due to its rarity, Kabuki Syndrome is not screened for in routine prenatal testing of blood tests, chorionic villus sampling (CVS), or amniocentesis.[medical citation needed] 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), it is possible to test for one of the specific mutations. However Kabuki syndome is usually not inherited and therefore most cases do not have a positive family history. Kabuki syndrome can have positive screening tests, such as cystic hygroma seen on nuchal translucency ultrasound screening, although these findings are non-specific and have a wide differential diagnosis.
There is no specific treatment for Kabuki syndrome. Treatment plans are customized to address the symptoms the individual is experiencing. For example, someone experiencing seizures will be treated with the standard anti-epilepsy therapies.
Additionally, patients with Kabuki syndrome should be evaluated and monitored to address problems that may develop, such as vision or hearing problems, or cognitive difficulties. If congenital heart disease is present, prophylactic antibiotics may be recommended before any procedures such as dental work that might cause infection.
There is no indication that the life expectancy of individuals with Kabuki syndrome is shortened, particularly if cardiac issues and infections are well-managed.
This section needs expansion. You can help by adding to it. (April 2018)
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- Niikawa, N.; Matsuura, N.; Fukushima, Y.; Ohsawa, T.; Kajii, T. (October 1981). "Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency". The Journal of Pediatrics. 99 (4): 565–569. ISSN 0022-3476. PMID 7277096.
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