What is Kabuki syndrome

TL;DR: Kabuki syndrome is a rare multisystem genetic disorder characterized by distinctive facial features, intellectual disability, and growth delays. It is typically caused by mutations in the KMT2D or KDM6A genes, which play a critical role in regulating how our genes are expressed during development.

What is Kabuki syndrome and how does it affect the body?

Kabuki syndrome is a congenital condition that affects many parts of the body. The name "Kabuki" originates from the unique facial appearance of affected individuals, which often resembles the makeup worn by actors in traditional Japanese Kabuki theater. These features typically include long eyelid fissures, everted lower eyelids, arched eyebrows, and a broad nasal tip. Beyond facial characteristics, Kabuki syndrome impacts multiple systems, frequently resulting in mild-to-moderate intellectual disability, skeletal abnormalities (such as joint hypermobility or scoliosis), and growth deficiency. Many individuals with Kabuki syndrome also experience feeding difficulties, heart defects, and differences in immune system function.

How common is Kabuki syndrome and who does it affect?

While exact figures are difficult to determine due to potential under-diagnosis, the estimated prevalence of Kabuki syndrome is approximately 1 in 32,000 to 1 in 86,000 individuals worldwide. It is a condition that does not show a preference for any specific ethnic or geographic background, and it occurs with equal frequency in males and females. Because it is a genetic condition present from birth, the signs are usually identified during infancy or early childhood, though the age of diagnosis can vary depending on the severity of the symptoms.

What causes Kabuki syndrome?

The underlying mechanism of Kabuki syndrome involves changes (mutations) in genes responsible for "epigenetic regulation"—the process that tells other genes when to turn on or off. The two primary genes identified are:

• KMT2D gene: Mutations in this gene account for approximately 60% to 80% of cases and are typically inherited in an autosomal dominant pattern.


• KDM6A gene: Mutations in this gene are associated with an X-linked inheritance pattern and account for a smaller percentage of cases.

In many instances, Kabuki syndrome occurs as a "de novo" mutation, meaning it is not inherited from either parent but occurs spontaneously in the egg or sperm cell at the time of conception.

How is Kabuki syndrome distinct from other conditions?

What differentiates Kabuki syndrome from other developmental disorders is its highly specific clinical "gestalt" or pattern of features. While many genetic syndromes present with global developmental delay, the combination of the characteristic facial morphology, unique dermatoglyphics (such as prominent fingertip pads), and specific skeletal findings helps clinicians distinguish it from other conditions like CHARGE syndrome or 22q11.2 deletion syndrome. Currently, 50 people with Kabuki syndrome have joined the DiseaseMaps community, providing a vital network for families navigating these diagnostic nuances.

Next steps

• Consult with a clinical geneticist to discuss genetic testing options and family planning.


• Coordinate care through a multidisciplinary team, including cardiologists, endocrinologists, and developmental pediatricians.


• Connect with the DiseaseMaps community to share experiences with other families living with Kabuki syndrome.


• Reach out to organizations like the All Things Kabuki foundation for patient-centered resources and support.

Medical disclaimer: This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

References

• NIH Genetic and Rare Diseases (GARD) Information Center: Kabuki Syndrome.


• Orphanet: Rare Disease Database (ORPHA:473).


• Online Mendelian Inheritance in Man (OMIM): #147920 (KMT2D-related).


• All Things Kabuki (Patient Advocacy Foundation).