ResourcesUnderstanding Kabuki Syndrome


What is Kabuki Syndrome?

Kabuki Syndrome is a rare congenital (something you are born with) disorder that affects multiple body systems. Many patients with Kabuki Syndrome have a distinct physical appearance characterized by a unique facial gestalt (appearance), short stature, and skeletal abnormalities. Patients may also have some level of intellectual disability or delay in addition to other abnormalities such as heart problems, hearing impairment, hypotonia (low muscle tone), feeding, and immune deficiency.

Kabuki Syndrome affects approximately 1 in 32,000 births worldwide and both males and females are equally affected. Each individual with Kabuki Syndrome presents in a unique manner and may need to seek treatment from a variety of different specialties to ensure all of their needs are being met. Patients may have a clinical diagnosis or may carry a pathogenic (disease causing) variant in either of the known Kabuki Syndrome genes (KMT2D of KDM6A).

What are the Symptoms?

Patients with Kabuki Syndrome generally present with a variety of symptoms, as the condition affects multiple body systems. Some of these symptoms are present at birth, while others are revealed as the patient grows older. Not every child with Kabuki Syndrome will have the same symptoms, but will have some* of the following:

  • Distinct facial gestalt (appearance) characterized by arched, incomplete eyebrows, elongated and wide-set eyes, thick eyelashes, a flat nasal tip, and large ears
  • Strabismus (poor eye muscle control leading to eye misalignment)
  • Small mouth or jaw, and/or a cleft or high arched palate
  • Hearing problems or hearing loss
  • Short fingers (especially the fifth fingers) and persistent fetal finger pads
  • Abnormalities of the teeth (missing, unusually shaped or misaligned teeth)
  • Skeletal abnormalities affecting the vertebrae that may result in mild spina bifida and/or scoliosis
  • Hypotonia (poor muscle tone) and extreme flexibility of joints
  • GI abnormalities leading to feeding complications, diarrhea, or constipation
  • Immune deficiency leading to frequent infections
  • Congenital heart defects (a heart defect the child is born with)
  • Endocrine abnormalities (an imbalance of hormones that leads to complications) such as hypoglycemia or hypothyroidism
  • Kidney and urinary tract abnormalities
  • Seizures
  • Early puberty and/or breast development in females

*Note: Not every patient will present with all of the following symptoms.

What are the causes?

Kabuki Syndrome is known to be caused by genetic changes in one of two genes, KMT2D or KDM6A. Most cases of Kabuki Syndrome are de novo, meaning that the variation happens spontaneously and is not passed down from parent to child. There are rare cases in which a Kabuki related gene variation has been passed from parent to child. In those cases, the family history is often positive for Kabuki Syndrome. Some patients receive a Kabuki Syndrome diagnosis despite not carrying a pathogenic variant in either of the two genes. This has led researchers and physicians to believe that there is likely one or more additional Kabuki Syndrome related genes yet to be discovered.

What is treatment like for a child with Kabuki Syndrome?

As the symptoms of Kabuki Syndrome vary widely, so do the treatment plans for many diagnosed individuals. Patients with a confirmed/suspected Kabuki Syndrome diagnosis should be fully evaluated by a health care provider to review all potentially affected systems. Patients may seek care from a combination of the following specialties: genetics, nutrition, neuropsychology, cardiology, endocrinology, ophthalmology, otolaryngology, audiology, urology, gastroenterology, dentistry, orthopedics, physical therapy, occupational therapy, social work, and others.

Coordination of visits to many different specialties across multiple clinics can be a challenging task for families. Because Kabuki Syndrome is a rare condition, many clinicians are not experienced in treating Kabuki Syndrome. Families and clinicians often work together to learn about Kabuki Syndrome and plan treatment for Kabuki Syndrome children.

Treatment at the Roya Kabuki Clinic

The Roya Kabuki Program has established a Kabuki Syndrome Clinic at Boston Children’s Hospital to streamline clinical care for patients with Kabuki Syndrome into a single medical home. We have appointed ‘Kabuki Champions’ or specialists in many of the subspecialties our patients typically see. As these specialists build their knowledge and experience in treating Kabuki Syndrome, they become able to provide expert care to our patients. This clinic model strengthens the awareness and education in the medical community while at the same time improves outcomes and experiences for families.

Every child with Kabuki Syndrome has a unique presentation of the condition. Therefore, every visit to the Roya Kabuki Clinic will be tailored to meet their exact need. Patients are always evaluated by Dr. Olaf Bodamer in Genetics, followed by evaluations from any necessary additional ‘Kabuki Champion(s)’. The specialists work together to create a coordinated plan for each patient. A program coordinator and social worker are available to help make the visits as simple as possible.

How are you diagnosed?

Some patients are diagnosed after having received a genetic test result that reveals a pathogenic variant (a change from normal genetic makeup that is known to be disease causing) in one of the two known Kabuki Syndrome genes (KMT2D and KDM6A). Other patients receive a clinical diagnosis of Kabuki Syndrome, meaning that after a medical evaluation a clinician (often a geneticist) has determined that the patient’s symptoms and medical concerns are compatible with Kabuki Syndrome. It is possible for patients with a clinical diagnosis of Kabuki Syndrome to go through the genetic testing process and test negative for pathogenic variants in the known Kabuki genes.

Some genetic testing laboratories offer a Kabuki Syndrome panel (focusing solely on finding variations in either KMT2D or KDM6A genes). Other genetic testing options can search for variations in the two known Kabuki genes as well as other genes related to similar conditions, while some testing looks at variations in the entire genetic makeup of a patient. A geneticist, who suspects possible Kabuki Syndrome may work with a patient family to order the appropriate genetic testing.