Searching for a Diagnosis?

Before the genes for Kabuki syndrome were discovered, clinicians would use clinical symptoms and features to determine if a person had Kabuki syndrome. This type of diagnosis is called a clinical diagnosis. While some people who were diagnosed before genetic testing was readily available still have a clinical diagnosis, revisiting a genetic counselor and finding the genetic cause of your syndrome has many benefits.

Genetic confirmation of Kabuki syndrome ensures that you will get the best medical care based on your specific type of Kabuki syndrome. Information about your genetics will allow your clinical team to:

• refine your treatment options, 
• avoid unnecessary tests, and 
• provide you with a more accurate prognosis.  

You will also become eligible to participate in clinical research which has many advantages including access to cutting edge treatments. In addition, this knowledge can empower patients and their families when evaluating recurrence risks during reproductive decision making.  

If you have a clinical diagnosis and would like to move forward with genetic testing, you and your provider can explore the genetic testing options above to decide which test is best for your situation.

Explore Start Genetic's parent toolkit for tips on how to start the conversation with your doctor.

You have options. New variants, or changes in the DNA spelling, of the KMT2D and KDM6A genes are still being discovered, even though researchers have made great progress in the last few decades. If your genetic test showed a variant that has not been discovered yet, it may have been classified as a variant of unknown significance (VUS). 

A VUS does not indicate if you do or do not have Kabuki syndrome, it means that there is a difference in the DNA compared to the general population, but not enough information is available to prove if that difference causes Kabuki syndrome. Variants that have been shown to cause Kabuki syndrome are called pathogenic variants.  Your clinician will consider many variables when deciding if your VUS is enough for them to diagnose you with Kabuki syndrome, but if you would like to determine if your VUS is in fact pathogenic, there are tests you and your clinician can explore.

Parental testing: Some families may be eligible to have their VUS re-classified as pathogenic through parental testing. For this test, both the biological mother and father are tested for Kabuki syndrome.  If both parents are healthy, show no symptoms of Kabuki syndrome and neither parent has the VUS discovered in their child, then the VUS is assumed to be causing the symptoms in the child and is re-classified as pathogenic and the child is diagnosed with Kabuki syndrome.

Methylation signature testing: People with Kabuki syndrome show a unique pattern of DNA methylation [1]. This test maps the methylation pattern across the DNA, to see if the methylation pattern matches the pattern found in  people with Kabuki syndrome. This can be an option for testing in people who do not qualify for parental testing or have otherwise inconclusive genetic testing results.

Greenwood Genetic Center is one company that offers methylation signature testing. Families can pursue this option with a provider and ask about self-pay, insurance, and institutional billing options. Contact us if you would like to connect with a Kabuki syndrome expert who can offer guidance on methylation signature testing.

There are many types of genetic tests that your clinician may offer based on your specific situation. Commonly offered genetic tests like karyotyping, fluorescence in situ hybridization (FISH), and micro-arrays may not be sensitive enough to pick up small changes in the DNA that cause Kabuki syndrome. Even if you have had some genetic testing done, it can be helpful to talk to your clinician about what other options there are for more sensitive genetic tests. 

Explore Start Genetic's parent toolkit for tips on how to start the conversation with your doctor.

If you do not have access to genetic testing, your clinician can move forward with a clinical diagnosis of Kabuki syndrome based on symptoms. Clinical diagnosis should be reserved for situations where genetic testing is not possible since genetic confirmation is now considered the gold standard for Kabuki syndrome diagnosis. 

New resources, like iHope, may offer opportunities for free genetic testing. Please contact us if we can help connect you with companies offering discounted or free testing.