*Also previously known as Kabuki-makeup syndrome (KMS) or Niikawa–Kuroki syndrome)
Is a 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. named Kabuki syndrome because of the facial resemblance of affected individuals to stage makeup used in kabuki, a Japanese traditional theatrical form.
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, 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. Mild to moderate intellectual disability and mild to severe developmental delay are often associated with Kabuki syndrome. Infants and young children often experience difficulties relating to hypotonia, feeding issues/failure to thrive, infections.
Kabuki syndrome is one of the Mendelian disorders of epigenetic machinery.Most cases of Kabuki syndrome occur de novo, that is, the parents are unaffected and the gene was mutated early in embryological development. It is classified as a Mendelian disorder because individuals who have a de novo mutation in a specific gene pass the mutation to offspring according to the laws of Mendelian inheritance. There are two known genes that cause Kabuki syndrome: KMT2D and KDM6A. However, about 30% of cases have no identifiable causative mutation.
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. A mutation in the KMT2D gene results in a non functional lysine (K)-specific methyltransferase 2D enzyme and demonstrates an autosomal dominant pattern of inheritance. Another 2-6% of cases are related to mutations in the KDM6A gene, located on the X chromosome. This mutation produces a nonfunctional lysine (K)-specific demethylase 6A enzyme and demonstrates an X-linked dominant pattern of inheritance.