Kabuki syndrome

What causes Kabuki syndrome?

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.

Last updated on 05-01-20

How is Kabuki syndrome inherited?

Kabuki syndrome is most often caused by a change (mutation) in the KMT2D gene, which is inherited in an autosomal dominant manner. 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. 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. In either case, a person with a disease-causing mutation may still pass it on to his/her offspring.

Last updated on 05-01-20

Can people with Kabuki syndrome have children?

Reports of Kabuki syndrome being passed down to children from both males and females imply that in at least some cases, fertility may not be affected. There have been parents of people with a diagnosis of Kabuki syndrome who have had some features compatible with mild Kabuki syndrome. However, because of the range of intellectual disability present (resulting in reduced possibilities to raise a family), it is not always clear whether fertility is impaired. It is known that some affected people have endocrine abnormalities which may affect fertility and reproduction.

People with questions about fertility and pregnancy are encouraged to speak with their health care provider or endocrinologist. A consultation with a genetics professional is also recommended for detailed information about how Kabuki syndrome may be inherited.

Last updated on 05-01-20

What is the long-term outlook for people with Kabuki syndrome?

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. Life expectancy is somewhat dependent on cardiac (heart) and immunologic complications.

Last updated on 05-01-20

Name: All Things Kabuki 5155 E Capon Circle
Wasilla, AK, 99654, United States
Phone: 907-360-8590 Email: http://www.allthingskabuki.org/contact Url: http://www.allthingskabuki.org/

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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