Diagnosis

Due to the August 2010 discovery of the MLL2 geneⁱ mutations responsible for approximately 75% of individuals with Kabuki Syndrome, a clinical blood test is now available to help with diagnosis. The National Center for Biotechnology Information provides a database which lists laboratories offering clinical testing, including prenatal testing. There may be other labs offering the testing which have not added their institution to this voluntary listing. If you are interested in having an individual with a clinical diagnosis of Kabuki be tested, you can ask your geneticist or another specialist to order the tests, perform the blood work (about 5 cc's of blood draw) and have it sent to one of those labs. In Canada, the test is not yet available but there have been situations where a geneticist may send the samples south of the border for testing. Please check with your geneticist to explore the options.

It is important to keep in mind that this test only diagnoses the 75% of cases that are caused by the MLL2 gene. It is possible that your result may be negative for the MLL2, but that the individual may still be believed to have Kabuki syndrome based on other presenting characteristics.

Initially, your geneticist will make a clinical diagnosis of Kabuki based on the recognition of four (out of five) main characteristics, with the distinct facial features being imperative.

• Facial features: long palpebral fissuresⁱ with eversionⁱ of outer third, arched eyebrows with sparse outer half, prominent eyelashes, prominent and/or misshapen ears, and depressed nasalⁱ tip
• Skeletal abnormalities: may include brachydactylyⁱ, brachymesophalangyⁱ and clindactylyⁱ of the fifth finger, and vertebral anomalies including scoliosisⁱ
• Dermatoglyphic abnormalities: including persistent finger fetal pads
• Intellectual disability (mild to moderate)
• Postnatal short stature

Kabuki is a complex syndrome with many associated findings. Co-existing conditions support a diagnosis but are not, separately, considered cardinalⁱ traits. Here is a list of some of the more common traits.

• Hypotonia
• Hyperextensible joints
• Feeding difficulties
• Behavioral difficulties
• Recurrent infections
• Hearing impaired and/or inner ear malformations
• Congenitalⁱ heart defects
• Renalⁱ/ urinary tract anomalies
• Other organ anomalies (less common) – malrotation of colon, anal atresiaⁱ, diaphragm eventrationⁱ or herniaⁱ
• Small mouth, micrognathiaⁱ, cleft or high arched palate
• Hypodontia, unusually shaped teeth, and misalignment
• Sudden weight gain during puberty years
• Early breast development and/or precocious (early) puberty
• Immunological abnormalities – may include Idiopathicⁱ Thrombocytopenic Purpuraⁱ, hemolytic anemiaⁱ, and growth hormone deficiency
• Seizures