What Is Kabuki Syndrome

Overview

Kabuki syndrome is an uncommon genetic disorder that impacts various bodily systems. The symptoms can manifest in different ways and intensities among individuals. The primary focus of treatment is to address symptoms and enhance overall well-being. Kabuki syndrome can affect facial features, skeletal structure, and other bodily systems. Although it is present from birth, the distinct features may not be immediately apparent and can emerge gradually, exhibiting variation among affected individuals. This article will explore the causes, symptoms and management options of Kabuki syndrome.

Kabuki syndrome is an uncommon genetic condition with an estimated occurrence of approximately 1 in 32,000 births.¹ While initially identified by Japanese medical professionals in 1981, there have been over 400 documented cases worldwide that have been genetically confirmed. The syndrome received its name "Kabuki" due to the resemblance of affected individuals' features to the distinctive makeup, known as kabuki, used in traditional Japanese theatre.

Causes of kabuki syndrome

Kabuki syndrome is the result of a genetic mutation affecting either the KMT2D or KDM6A genes.⁵  In certain instances, the syndrome can be inherited within families. When inherited, it typically follows an autosomal dominant inheritance pattern, meaning that the affected individual only needs to receive one altered gene from a single parent to develop the syndrome.

However, in the majority of cases, particularly those caused by mutations in the KMT2D gene, there is no known family history of the syndrome. This suggests that the mutation occurs spontaneously and randomly rather than being passed down from parents.

Signs and symptoms of kabuki syndrome

Kabuki syndrome impacts multiple body systems, and the following are some of the symptoms and characteristics associated with it. 

Facial features 

 Common physical traits include:  

• Wide-spaced eyes 
• A flattened nose
• Cleft palate or high palate

Other notable facial features may include: 

• Prominent or low-set ears 
• Wide openings between the eyelids (palpebral fissures) 
• Outwardly turned lower eyelids
• Distinctive eyebrow arch
• Prominent eyelashes
• Pit-like depressions in the lips (lip pits)
• A blue tinge to the whites of the eyes (blue sclerae)
• Strabismus (squint), micrognathia (undersized jaw)
• Microcephaly (smaller-than-average head size). 

Growth and skeletal system features:

Kabuki syndrome often involves musculoskeletal issues such as short stature, scoliosis, shorter fingers than average, and hypermobile joints. Children with this syndrome may also experience growth delays after birth. 

Intellectual disability: 

Many children with Kabuki syndrome exhibit mild to moderate intellectual disabilities or learning difficulties, although some may not have intellectual impairments. 

Other features 

Additional potential health effects associated with Kabuki syndrome include:  

• Cardiovascular conditions like narrowing of the aorta or defects in the atrial or ventricular septum
• Hearing loss
• Kidney abnormalities such as renal dysplasia or hydronephrosis
• Missing teeth
• Immune system issues like idiopathic thrombocytopenic purpura
• Undescended testicles
• Recurrent ear infections
• Epilepsy
• Hypotonia (low muscle tone)
• Precocious puberty
• Weight gain during puberty
• Sleep difficulties
• Behavioural issues
• Anxiety disorders²
• Attention deficit hyperactivity disorder (ADHD)
• Autism spectrum disorder³

Management and treatment for kabuki syndrome

At present, there is no known cure for Kabuki syndrome. Therefore, the primary objective of treatment is to alleviate symptoms and minimize the risk of complications.⁴ The following treatment options are available:

Medications 

Various medications may be prescribed to manage specific symptoms of Kabuki syndrome, including antiepileptics to control seizures and growth hormones to address growth issues. 

Surgery 

Surgical interventions may be necessary to correct heart defects, address hearing loss, or reconstruct abnormal physical features like prominent low-set ears, strabismus (misaligned eyes), and undescended testicles.

Therapies 

Different therapeutic approaches may be beneficial in managing Kabuki syndrome. These may include physical therapy to improve motor skills and mobility, occupational therapy to enhance daily living skills and independence, and speech therapy to address speech and communication difficulties. 

Orthopaedic treatments 

For individuals with joint hypermobility or scoliosis, orthopaedic interventions such as surgery may be considered to provide support and alleviate discomfort. 

Ophthalmological care 

Regular eye examinations and appropriate ophthalmological interventions are important to address any eye and vision-related issues associated with Kabuki syndrome. 

Diagnosis

The diagnosis of Kabuki syndrome can be achieved through two approaches:⁴

Genetic testing 

Genetic testing involves analyzing blood samples to identify any mutations in the KMT2D or KDM6A genes. If the initial blood test does not indicate such mutations, further testing may be conducted by a healthcare professional to explore additional possibilities. 

Physical examination 

A physical examination is conducted by a paediatrician to assess the overall health of the child, observe specific physical characteristics associated with Kabuki syndrome, and evaluate other signs that may contribute to the diagnosis. 

FAQs

How can I prevent Kabuki syndrome?

There are no known preventive measures or strategies to prevent Kabuki syndrome. The syndrome typically occurs due to genetic mutations that happen randomly or are inherited from a parent with Kabuki syndrome. Since the underlying causes are not well understood, there are no specific actions that can be taken to prevent its occurrence.

How common is kabuki syndrome

Kabuki syndrome is an uncommon genetic condition with an estimated occurrence of approximately 1 in 32,000 births.¹

Who is at risk of kabuki syndrome?

In the majority of cases, Kabuki syndrome occurs spontaneously without any identifiable risk factors or preventive measures. However, when the syndrome is inherited, the primary risk factor is having a parent with Kabuki syndrome who carries the mutated gene in their DNA. For instance, individuals who possess one copy of the mutated KMT2D gene have a 50% likelihood of passing it on to their child, who would then develop Kabuki syndrome as well. 

When should I see a doctor?

If you have concerns about genetic conditions or family history, it is advisable to consult with a healthcare professional or a genetic counsellor who can provide personalized guidance and information.

Summary

Kabuki syndrome is an uncommon genetic disorder that affects various bodily systems. It is typically diagnosed through genetic testing and physical examinations. The syndrome can cause distinct facial features, skeletal abnormalities, intellectual disabilities, and other health issues. 

Currently, there is no cure for Kabuki syndrome, but treatments focus on managing symptoms and improving quality of life. Medications, surgeries, therapies, orthopaedic interventions, and ophthalmological care are among the available management options. 

Kabuki syndrome usually occurs randomly, but it can be inherited when a parent carries the mutated gene. There are no known preventive measures for the syndrome. If there are concerns, it is recommended to seek medical advice from a healthcare professional or genetic counsellor.