Kabuki syndrome is a rare, congenital disorder characterized by a wide range of physical and developmental differences. The condition affects multiple body systems and is present from birth, though some signs may not become apparent for several years.
Genetic Origins of Kabuki Syndrome
The foundation of Kabuki syndrome lies in mutations within specific genes responsible for development. Approximately 75% of diagnosed cases are caused by a change in the KMT2D gene, referred to as Kabuki syndrome type 1. A smaller portion, about 3% to 5%, result from mutations in the KDM6A gene, leading to Kabuki syndrome type 2. Both of these genes provide instructions for creating enzymes that modify histones, which are proteins that package DNA into chromosomes.
These histone-modifying enzymes play a part in controlling the activity of other genes. By adding or removing chemical marks on histones, they help determine which genes are turned “on” or “off” during embryonic development. A mutation in either KMT2D or KDM6A disrupts this regulatory process, affecting normal growth and development across multiple organ systems.
Most instances of Kabuki syndrome are de novo, meaning the genetic mutation occurs for the first time in the affected individual and is not inherited. When it is inherited, the pattern differs depending on the gene involved. Mutations in KMT2D follow an autosomal dominant pattern, where only one copy of the altered gene is needed for the disorder. Because the KDM6A gene is on the X chromosome, mutations in it follow an X-linked dominant inheritance pattern.
Core Physical and Developmental Features
The signs of Kabuki syndrome are diverse, with features spanning physical appearance, growth, and cognitive development. These manifestations are present in varying degrees and combinations, contributing to the unique presentation of each individual.
Distinctive Facial Features
The most recognizable characteristics are often the facial features, which led to the syndrome’s name due to a resemblance to the makeup used in traditional Japanese theater. These include long openings between the eyelids, with the outer part of the lower eyelid often turned outward. Individuals commonly have eyebrows that are arched and broad, sometimes with thinning on the outer edge. Other features include a short nasal columella resulting in a flattened nasal tip, and large or prominent ears.
Growth and Skeletal Differences
Growth delays are a frequent aspect of Kabuki syndrome, resulting in short stature that becomes more apparent after birth. Skeletal differences are also common, including short fingers (brachydactyly), curvature of the spine (scoliosis), and joint hypermobility, where joints have an unusually large range of movement.
Developmental and Neurological Aspects
Developmental delays are a central component of the syndrome, particularly in achieving motor skills and speech milestones. The degree of intellectual disability associated with Kabuki syndrome varies, ranging from mild to moderate. Some individuals may also experience neurological issues such as seizures. Hypotonia, or low muscle tone, is another common finding that can contribute to feeding difficulties in infancy and delays in motor development.
Associated Health Conditions
Individuals with Kabuki syndrome often have health issues affecting various organ systems.
- Congenital heart defects
- Problems with the kidneys or urinary tract
- An increased risk of infections, which may be linked to the immune system
- Hearing loss and dental abnormalities, like widely spaced teeth
The Diagnostic Process
The diagnostic process for Kabuki syndrome begins with recognizing its characteristic clinical features. A clinical geneticist will conduct a physical evaluation, noting the distinctive facial features, growth patterns, and skeletal anomalies. The combination of these signs often leads to a suspected diagnosis.
Molecular genetic testing is used to confirm the diagnosis. This testing analyzes DNA to identify a mutation in one of the two known causative genes: KMT2D or KDM6A. Identifying a mutation in one of these genes provides a definitive diagnosis and helps inform discussions about inheritance patterns.
A diagnosis can be made based on clinical findings alone, even if genetic testing does not reveal a mutation. This can occur because other, yet-to-be-identified genes may cause the syndrome. In these cases, the presence of the core features is sufficient for a clinical diagnosis by an experienced geneticist.
Therapeutic and Medical Management
There is no specific cure for Kabuki syndrome, so management focuses on addressing the individual’s symptoms and supporting their development. This requires a coordinated, multidisciplinary team of specialists to provide comprehensive care. The approach is proactive, aiming to monitor for complications and provide support as early as possible.
Early intervention services are a primary component of management. Physical therapy helps with low muscle tone and motor skills, while occupational therapy assists with fine motor coordination and daily living activities. Speech therapy is necessary to address language delays and can also help with feeding difficulties. These therapies are most effective when started early.
Regular monitoring by various medical specialists is a standard part of the care plan. A cardiologist will evaluate and manage congenital heart defects. Nephrologists may be involved to monitor kidney function, and immunologists can help manage the increased susceptibility to infections. Regular hearing screenings with an audiologist are also recommended.
Educational and social support systems are also important. Tailored educational strategies, often in an Individualized Education Plan (IEP), help address learning differences. Family support through counseling and connection with advocacy groups can provide valuable resources and a sense of community.