Kabuki Syndrome - A Rare Congenital Disease

What Is Kabuki Syndrome?

Kabuki syndrome is a rare, congenital multiorgan disorder that is characterized by various abnormalities since birth including unique facial features, growth retardation, varying grades of intellectual disability, skeletal defects, short stature, seizures, and cognitive impairment. The disorder was previously referred to as Kabuki-makeup syndrome (KMS) or Niilawa-Kuroki syndrome. It is characterized by distinctive facial features including eyebrows that are arched, long eyelashes along with long palpebral fissures, flattened nose tip, cleft palate, and large bulging earlobes. The affected children have a close resemblance in their characteristic facial features to stage makeup that is applied by traditional Japanese Kabuki theater artists, hence the name.

What Is the Cause of Kabuki Syndrome?

Kabuki syndrome is a congenital disorder, meaning it is present since birth. It usually occurs due to a mutation in the gene histone-lysine N-methyltransferase 2D (formerly known as MLL2). The affected child carries two copies of this variant gene and Kabuki syndrome is caused when only one of the two gene copies is altered. It is an autosomal dominant inherited disorder. However, in many children affected with Kabuki syndrome, the disease has manifested itself as a new genetic disorder instead of being inherited from either parent.

This gene is responsible for providing instructions for synthesizing an enzyme, called lysine-specific methyltransferase 2D. This enzyme is present in multiple organs and tissues of the body. Lysine-specific methyltransferase 2D enzymes function as histone methyltransferases. Histone methyltransferases are the enzymes that are responsible for modifying proteins known as histones. The biological role of histones is to structurally attach (bind) to deoxyribonucleic acid and provide shape and structure to the chromosomes. Histone methyltransferases regulate the activity of certain genes by a process called methylation where a molecule known as a methyl group is added to histones. Lysine-specific methyltransferase 2D activates certain genes that are crucial for the development process. An alteration in the gene histone-lysine N-methyltransferase 2D is not detected in all the affected children affected with Kabuki syndrome. In some individuals, the cause of the disease is not known.

What Is the Epidemiology of Kabuki Syndrome?

Kabuki syndrome is a rare syndrome with an approximate frequency of only one in every 32000 new births. Males and females are equally affected by the disorder. The disease remains underdiagnosed many times.

What Are the Symptoms of Kabuki Syndrome?

Kabuki syndrome has numerous clinical features, but all the features are not present in the child since birth. The most common signs and symptoms include:

• A unique set of facial morphological features, including eyes that are broadly spaced, low-set or protruding ears, exaggerated arched eyebrows, nose tip flattened, and a cleft palate.

• Stature is shortened.

• Skeletal defects, such as scoliosis (lateral bending of the spine), small fingers, or very flexible joints.

• Mild to severe disability in the intelligence of the child.

There are other health issues associated with Kabuki syndrome includes:

• Cardiac defects such as narrowing of the aorta (the main artery that carries oxygenated blood), or atrial septal defects between the right and left heart chambers.

• Loss of hearing.

• Renal abnormalities.

• Teeth problems, such as missing teeth or fractured teeth.

• Optical disturbances such as drooping eyelids (ptosis) or strabismus (abnormal eye alignment).

• Immune system malfunctioning, such as the autoimmune disorder idiopathic thrombocytopenic purpura (a bleeding disorder of platelets).

• Microcephaly (small head).

• Cryptorchidism.

• Infections of the middle ear.

• Seizures.

• Behavioral changes.

• Early-onset puberty.

• Considerable weight gain on achieving puberty.

How Is the Diagnosis of Kabuki Syndrome Made?

The diagnosis of Kabuki syndrome is difficult to establish because of three main reasons:

• Every child has got a unique set of facial morphological features for the condition. Therefore, every child presents the disorder differently.

• All the distinctive facial characteristics are not developed at birth but usually develop over a period of time.

• The condition is very rare so not much data is available on the disease.

The diagnosis usually depends on the distinctive facial features and other signs and symptoms that are suggestive of Kabuki syndrome acquired by the child. A geneticist (a biologist who studies genetics) usually makes the diagnosis. Genetic testing (whole genome sequencing) of the histone-lysine N-methyltransferase 2D gene can also be carried out to establish the diagnosis.

What Is the Treatment of Kabuki Syndrome?

There is no known cure for Kabuki syndrome. Treatment is aimed at reducing the risks associated with complications of the disorder and improving the quality of life of the affected individuals.

The various treatment options include:

• Surgery to correct a heart defect.

• Medications to control epileptic seizures.

• Orthopedic surgical treatment to treat lateral bending of the spine and extremely flexible joints.

• Restorative dental treatment.

• Cosmetic facial surgery.

• Eye tests on a regular basis and treatment.

• Physiotherapy to strengthen muscles.

• Occupational therapy to improve cognitive, fine sensory, and fine motor skills.

• Correction of speech.

• Training in sign language.

• Training on social life skills.

• Therapy on behavior modification.

• Special teachers to assist in education.

What Is the Prognosis of Kabuki Syndrome?

Kabuki syndrome is an extremely rare genetic disorder so very limited information is available on the long-term prognosis (outlook) of the affected individual. It was observed that a few adults, suffering from Kabuki syndrome, could manage their daily life activities and part-time jobs. But support staff are required to take care of them. An individual suffering from Kabuki syndrome usually appears to have a normal span of life, but he might be suffering from other ongoing medical issues associated with the disorder. These medical problems require quick medical treatment. People affected with Kabuki syndrome usually experience obesity in adolescent age or even in adulthood, which poses a high risk of health complications such as heart disease and diabetes mellitus. Therefore, weight control is critical.

Conclusion

Kabuki syndrome is a rare congenital disorder that usually runs in families. The diagnosis of the disease is usually made on the basis of distinctive facial features and skeletal abnormalities. There is no cure for the disease. Efforts are made by the doctor to improve the quality of life and reduce complications. Genetic counseling can also be opted for to achieve emotional support.