Kabuki syndrome

Kabuki syndrome is a rare genetic disorder with a range of characteristics, including intellectual disability, distinctive facial features and skeletal abnormalities. Estimates suggest it occurs in about one in every 32,000 births. However, Kabuki syndrome is thought to be underdiagnosed, so it could be more common.

The condition affects males and females equally, and there is no cure. It is also known as Niikawa-Kuroki syndrome.

Symptoms of Kabuki syndrome#

Kabuki syndrome has a wide range of characteristics, but not all are present in every child with the condition. The most common include:

• A distinctive set of facial features, including widely spaced eyes, low-set or prominent ears, an exaggerated eyebrow arch, a flattened nose tip, and a very high palate or cleft palate
• Intellectual disability, ranging from mild to severe
• Short stature
• Skeletal abnormalities, such as scoliosis, short fingers or lax joints

Other health problems with Kabuki syndrome#

Kabuki syndrome may be associated with other health problems, including:

• Heart defects, such as coarctation (narrowing) of the aorta, or ventricular or atrial septal defects (holes between the right and left heart chambers)
• Immune system dysfunction, such as the autoimmune disease idiopathic thrombocytopenic purpura (ITP), a bleeding disorder
• Hearing loss
• Kidney abnormalities
• Dental problems, such as missing or misshapen teeth
• Eye problems, such as a drooping eyelid (ptosis) or strabismus
• A small skull (microcephaly)
• Undescended testicles
• Ongoing middle ear infections
• Epilepsy
• Behaviour problems
• Early puberty
• Substantial weight gain at puberty

Causes of Kabuki syndrome#

Kabuki syndrome is usually caused by a change in the gene KMT2D (formerly known as MLL2). Everyone has two copies of the KMT2D gene, and Kabuki syndrome occurs when only one of the two copies is changed. This is an ‘autosomal dominant’ inheritance pattern. However, in most children with Kabuki syndrome, the change has occurred as a new genetic change rather than being inherited from a parent.

A change in the KMT2D gene is not identified in all children with suspected Kabuki syndrome. Changes in a second gene, DKM6A, are a less common cause of Kabuki syndrome.

Diagnosis of Kabuki syndrome#

Kabuki syndrome is difficult to diagnose for three main reasons:

• Every child with the condition presents with a slightly different set of characteristics.
• Rather than being present at birth, characteristics may develop over time.
• Many doctors may not be familiar with Kabuki syndrome because the condition is so rare.

A geneticist usually makes the diagnosis based on the child having distinctive facial features and other signs suggestive of Kabuki syndrome. Genetic testing of the KMT2D gene can be used to confirm the diagnosis.

Treatment of Kabuki syndrome#

Kabuki syndrome is permanent and there is no cure. Treatment aims to reduce the risk of complications and improve quality of life. Options may include:

• Surgical treatment, for example an operation to correct a heart problem
• Medication to manage epileptic seizures
• Orthopaedic treatment for scoliosis and joint laxity
• Restorative and cosmetic dental treatment
• Regular eye examinations and treatment
• Physical therapy to strengthen muscles
• Occupational therapy to improve fine motor skills
• Speech therapy
• Sign language training
• Social skills training
• Behaviour modification therapy
• Special education assistance
• Cosmetic surgery, for example to pin back prominent ears

Long-term outlook for Kabuki syndrome#

Since Kabuki syndrome is so rare, there is limited information on the long-term outlook. One study of three adults with Kabuki syndrome found that while they could manage day-to-day life and hold part-time jobs, they still needed supported care accommodation.

A person with Kabuki syndrome appears to have a normal life span, but is likely to have ongoing medical problems associated with the condition that will require medical management. People with Kabuki syndrome may also develop obesity in adolescence or adulthood, which increases the risk of a range of health problems, including cardiovascular disease and diabetes. For this reason, weight management is important.

Genetic counselling and Kabuki syndrome#

If your child or another family member has been diagnosed with Kabuki syndrome, or if the condition runs in your family, it can be helpful to speak to a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics. As well as providing emotional support, they can help you understand Kabuki syndrome and what causes it, how it is inherited, and what a diagnosis means for your child’s health and development and for your family.

Genetic counsellors are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs. If Kabuki syndrome runs in your family, a genetic counsellor can explain what genetic testing options are available to you and other family members. You may also choose to see a genetic counsellor if you are planning a family, to find out your risk of passing the condition on to your child, or to arrange prenatal tests.

Key points#

• Kabuki syndrome is thought to be underdiagnosed, so it could be more common than estimates suggest.
• Changes in a second gene, DKM6A, are a less common cause of Kabuki syndrome.
• Many doctors may not be familiar with Kabuki syndrome because the condition is so rare.
• Treatment aims to reduce the risk of complications and improve quality of life.
• Weight management is important.

Where to get help#