Searching for a Diagnosis?

If you or a loved one is experiencing multiple health problems or symptoms, finding an accurate diagnosis can be time consuming and frustrating. If you have been diagnosed clinically with Kabuki syndrome or have a VUS, we have resources for you, too.

Receiving a diagnosis is important for developing a treatment plan, understanding your prognosis, and gathering a support system. It takes 4-5 years on average for families affected by rare diseases to receive an accurate diagnosis. [1]

We hope to shorten your diagnostic odyssey by offering these resources.

Genetic Testing for Kabuki Syndrome

Scientists have discovered the genes that cause Kabuki syndrome, making it possible to determine if you or a loved one has Kabuki syndrome through genetic testing.  Genetic tests will examine the sequence, or look for spelling errors, in the DNA in a blood, tissue, or saliva sample to see if there is anything atypical that could be causing Kabuki syndrome. Here are some options you and your healthcare provider can explore for genetic testing:

Targeted Gene Sequencing

 Genetic testing that only sequences the two genes (KMT2D and KDM6A) associated with Kabuki syndrome.  This test is designed to diagnose only Kabuki syndrome.

In North America, Invitae is one company that offers this testing. Estimated cost to families is $250 or less. If you/your child is experiencing immune system problems, you may be eligible for free genetic testing through one of these sponsored programs: PATH4WARD or NavigateAPDS.

 

Panel Testing

Genetic testing that sequences specific genes associated with a group of conditions that have a similar presentation of symptoms. Common Kabuki syndrome panels test for the two genes associated with Kabuki syndrome as well as genes associated with CHARGE syndrome, Larsen syndrome, Au-Kline syndrome, KBG syndrome, and others. There are multiple labs that offer Kabuki syndrome panel testing, so the genes included in each panel will vary. This test is designed to diagnose Kabuki syndrome and a limited number of similar disorders.

Other panel testing is more broad and examines many genes associated with a symptom. Some of these that include Kabuki syndrome might be: a hypotonia panel, global developmental delay/intellectual disability panel, congenital heart disease panel, immunodeficiency panel, and more.

Whole Exome Sequencing

A more comprehensive test that sequences the most important parts (protein-coding regions) of the DNA.  This test is designed to give you information about the genes that cause Kabuki syndrome as well as many other genes that cause alternative disorders and syndromes.  This technique can lead to a Kabuki syndrome diagnosis or an alternative diagnosis.

In the United States, GeneDx is one company that offers this testing with flexible billing and payment options.

Whole Genome Sequencing

A fully comprehensive test that sequences all of the DNA. This is the most thorough test to give information about differences anywhere in the DNA. This technique can lead to a Kabuki syndrome diagnosis or an alternative diagnosis.

In the United States, GeneDx is one company that offers this testing with flexible billing and payment options.

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 this testing and can accept samples from the U.S., Canada, and possibly other countries. 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.

Discover the Power in Your Diagnosis

Watch as Jessica Weatherstone, Kabuki syndrome parent and KSF Program Manager, walks you through the evolution of Kabuki syndrome diagnostics and why your type of diagnosis matters.

During this live webinar, we also launched the newest chapter of Kabuki syndrome diagnostics: AI facial recognition that can drastically decrease the time spent searching for a diagnosis. Hellen Lesmann, GestaltMatcher, illustrated how genetically diagnosed families can participate in this global study that can help improve the care of others. Plus, KSF Research Ambassador Kristin Anzelc shared her diagnostic journey and research experiences. 

Watch on YouTube

Frequently Asked Questions

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.

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. 

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. 

Have More Questions?

Our mission is to accelerate research that leads to treatments for every type of Kabuki syndrome. The Kabuki Syndrome Foundation does not provide diagnostic or medical recommendations. The resources above are shared for educational purposes only. We welcome your questions.

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