Kabuki Syndrome

What is Kabuki syndrome?

Kabuki syndrome is a rare genetic condition that can affect many different parts of your child’s body. Although the disease is present from birth (congenital), your baby may or may not show any signs of the condition as a newborn. It may take several years for symptoms to develop. The specific features and the severity of your child’s condition may vary. Your child may have:

• Distinctive facial characteristics.
• Skeletal abnormalities.
• Growth delays.
• Intellectual disabilities.

Two Japanese scientists discovered Kabuki syndrome in 1981. One of the scientists named the disease Kabuki makeup syndrome because the facial features of many children with the condition resembled the stage makeup worn by Kabuki dancers. Kabuki is a traditional form of Japanese theater. Scientists have since dropped the word “makeup,” and the preferred name for the condition is Kabuki syndrome.

Who does Kabuki syndrome affect?

Kabuki syndrome is a genetic condition that can affect anyone. Although researchers in Japan first discovered the disease, healthcare providers now diagnose the condition in people of many different ethnicities.

How rare is Kabuki syndrome?

Kabuki syndrome is very rare but exact numbers are unknown. Around the world, estimates range from between 1 in 32,000 and 1 in 86,000 newborns born with the condition. Scientists believe between 3,000 and 30,000 people are living with the disease in the United States.

What are the symptoms of Kabuki syndrome?

Some Kabuki syndrome signs are present at birth (congenital). Others become more apparent as your child gets older. The specific signs and symptoms your child develops may vary. The severity of your child’s symptoms can vary as well. Kabuki syndrome can affect a wide variety of your child’s organs and body systems.

The five most common features of Kabuki syndrome include:

• Distinctive facial features
  • Abnormally long openings between your child’s eyelids (palpebral fissures) with an abnormal curve on the outside edges.
  • Highly arched and broad eyebrows with sparse hair on the ends.
  • A short notch between your child’s nose and lips with a flat nose.
  • Large ears, ears that stick out or ears that are cupped.
• Skeletal abnormalities
  • Spine abnormalities, such as an abnormal curvature of your child’s spine (scoliosis or kyphosis).
  • Short fingers and toes (brachydactyly).
  • Bent fifth (pinky) finger (clinodactyly).
• Fleshy pads at the tips of your child’s fingers (usually present in fetuses and resolve after birth, but persistent in those with Kabuki syndrome).
• Mild to moderate intellectual disability.
• Growth delay after birth.

Your child may develop other signs and symptoms depending on the severity of their condition.

Facial features

• Long, thick eyelashes.
• Bluish tinge to the whites of your child’s eyes (blue sclera).
• Drooping of your child’s eyelids (ptosis).
• Eyes that don’t look in the same direction at the same time (strabismus).
• Cleft lip or cleft palate.
• Depressions near your child’s ears (ear pits).
• An abnormally small jaw (micrognathia).
• Dental abnormalities such as widely spaced teeth or fewer teeth than normal.

Musculoskeletal abnormalities

• Loose joints (joint hypermobility).
• Skull (cranial) malformations.

Neurological features

• Seizures.
• Speech delays.
• Weak muscle tone (hypotonia).

Growth, gastrointestinal and feeding issues

• Feeding difficulties.
• Poor sucking.
• Poor swallowing.
• Malabsorption.
• Gastroesophageal reflux.
• Short stature.

Some children with Kabuki syndrome may develop behavioral issues. The most common psychiatric/behavioral issues are found in a subset of children with the condition. These include ADHD/hyperactivity, anxiety disorder, self-harming behaviors, sleep disturbances and autism. Signs of these issues may include:

• Obsessive-compulsive traits.
• A tendency to fixate on certain objects or activities.
• Sensitivity toward stimuli such as certain smells, noises or textures.
• Sensory processing disorder, which is the inability to accurately organize sensory information.
• A need for oral stimulation, such as chewing on non-food items.
• Mild depression.

Kabuki syndrome can affect multiple other organs and body systems. Other signs of the condition may include:

• Recurrent infections (such as ear infections, sinus infections or pneumonia).
• Hearing loss.
• Precocious (early) puberty.
• Kidney abnormalities.
• Gastrointestinal abnormalities.
• Immunological deficiencies.
• Heart defects.
• Persistently low blood sugar after birth.

What causes Kabuki syndrome?

A genetic change or variant (mutation) in one of two genes causes Kabuki syndrome. A mutation of the KMT2D gene (formerly known as MLL2) is responsible for about 75% of all cases. This is sometimes called Kabuki syndrome type 1. A mutation of the KDM6A gene causes the condition in 3% to 5% of cases. This is called Kabuki syndrome type 2.

Both of these genes give your cells instructions to make certain enzymes that alter proteins called histones. Histones attach to your DNA and give your chromosomes their shape. By altering the histones, the enzymes can control your gene activity. These enzymes are important for development.

A mutation in either the KMT2D gene or the KDM6A gene leads to the absence of these enzymes. When your body lacks these enzymes, gene activation can’t occur. This results in the characteristics and abnormalities of development commonly seen in the condition.

In some cases, people diagnosed with Kabuki syndrome don’t have a mutation in either of these genes. The cause of the disease isn’t known in these individuals.

How is Kabuki syndrome inherited?

When a mutation in the KMT2D gene causes the condition, it’s inherited in an autosomal dominant pattern. This means one copy of the mutated gene is enough to cause the disorder.

When a mutation in the KDM6A gene causes the condition, it’s inherited in an X-linked dominant pattern. The KDM6A gene is located on the X chromosome. The X chromosome is one of the two sex chromosomes. In people with two X chromosomes, a mutation in one of the two copies of the gene is enough to cause the disorder. In people with only one X chromosome, a mutation in the only copy of the gene causes the disorder.

Most cases of Kabuki syndrome result from a new mutation (de novo) in one of these genes. They happen for the first time in people with no biological family history of the disorder. However, there have been a few cases of a person inheriting the mutation from one affected parent.

How is Kabuki syndrome diagnosed?

Your child’s healthcare provider will obtain a detailed history and perform a physical examination. They’ll look for specific signs and symptoms of the condition. They’ll look for distinctive facial characteristics, musculoskeletal abnormalities and neurological disabilities. They’ll also ask about your child’s biological family history.

To confirm a diagnosis, your child’s provider will request a genetic test. To perform the test, they’ll obtain a small sample of your child’s blood to look for genetic changes in the genes that cause Kabuki syndrome.

Some people with Kabuki syndrome don’t have a genetic mutation in either gene. Your child’s provider may request other blood tests or chromosomal studies to rule out other conditions.

How is Kabuki syndrome treated?

There’s no cure for Kabuki syndrome. Treatment for the condition focuses on alleviating your child’s specific symptoms. It can also help reduce the risk of complications. Treatment options may include:

• Early interventions: Enrollment in supportive services and education to improve cognitive development.
• Physical, occupational and speech therapy: Physical therapy can help strengthen your child’s muscles. Occupational therapy helps improve their fine motor skills. Speech therapy enhances their speech and language capabilities.
• ABA and sensory integration therapy: Therapies to help with autism spectrum disorder and sensory issues.
• Gastronomy tube placement or supplemental growth hormone: To help with feeding difficulties.
• Hearing aids: To help improve hearing loss.
• Medication: To help control seizures, gastrointestinal reflux, ADHD or other symptoms.
• Surgery: For joint scoliosis, heart defects, cleft palate and other surgical needs.

How can I prevent Kabuki syndrome?

You can’t prevent Kabuki syndrome because it’s a genetic condition. The genetic mutation that causes this condition most often happens randomly. There’s no biological family history of the condition, which makes it difficult to predict.

Is Kabuki syndrome life-threatening?

The outlook for Kabuki syndrome depends on the severity of your child’s condition. The disease can affect many different parts of your child’s body, but it won’t necessarily affect all of them. Treatment for your child’s specific symptoms can help them live a normal life. You should ask your child’s healthcare provider about their specific life expectancy.

There are adults with the disease that appear to have a normal lifespan. But since the condition is so rare, there isn’t a lot of research on the life expectancy of Kabuki syndrome. One very small study found that adults with Kabuki syndrome could manage day-to-day life and hold part-time jobs. But they still needed supportive care.

How do I take care of my child?

If your child has Kabuki syndrome, take some time to learn everything you can about the condition. Work with your child’s healthcare provider to find out what you can do to ensure your child receives the best possible care. You may want to join a support group in your community for families of children with rare diseases.

What questions should I ask my child’s healthcare provider?

• How rare is my child’s condition?
• How severe are my child’s symptoms?
• What kind of treatment does my child need?
• Does my child need surgery?
• What is my child’s life expectancy?