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Kabuki syndrome

Medically Reviewed

A congenital disorder with facial features, skeletal anomalies, and intellectual disability.

Overview

Kabuki syndrome is a rare genetic disorder characterized by distinct facial features, growth delays, intellectual disability, and a variety of congenital anomalies. First described in Japan in 1981, the syndrome was named after the traditional Japanese Kabuki theatre due to the resemblance of the facial features to Kabuki makeup. The condition affects multiple organ systems and presents a broad spectrum of clinical manifestations, which can vary in severity among affected individuals.

Causes

Kabuki syndrome is most commonly caused by mutations in the KMT2D gene (previously known as MLL2), which is inherited in an autosomal dominant pattern. Mutations in the KDM6A gene, inherited in an X-linked dominant pattern, are also associated with the condition. These genes play crucial roles in chromatin remodeling and gene expression regulation during development, and their disruption can lead to the diverse phenotypic features observed in Kabuki syndrome.

Symptoms

The clinical features of Kabuki syndrome vary widely but typically include:

  • Distinctive facial features such as arched eyebrows, long eyelashes, long palpebral fissures, and a depressed nasal tip

  • Developmental delay and intellectual disability, often mild to moderate

  • Postnatal growth deficiency leading to short stature

  • Skeletal anomalies, such as joint laxity and spinal abnormalities

  • Persistent fingertip pads

  • Congenital heart defects

  • Hearing loss

  • Feeding difficulties and poor weight gain in infancy

  • Immunological issues, including increased susceptibility to infections and autoimmune diseases

Diagnosis

The diagnosis of Kabuki syndrome is based on clinical features and confirmed through genetic testing. A comprehensive clinical evaluation, including a physical examination focusing on dysmorphic features and developmental history, is essential. Molecular genetic testing can identify pathogenic variants in the KMT2D or KDM6A genes, confirming the diagnosis. In some cases, imaging and additional laboratory assessments may be necessary to evaluate organ system involvement.

Treatment

There is no cure for Kabuki syndrome, and treatment is symptomatic and supportive. Management typically involves a multidisciplinary team and may include:

  • Developmental therapies such as physical, occupational, and speech therapy

  • Educational support tailored to the individual’s needs

  • Management of congenital anomalies, such as surgical correction of heart defects

  • Hearing aids or cochlear implants for hearing loss

  • Monitoring and treatment of autoimmune disorders or infections

  • Endocrinological evaluation for growth hormone therapy in some cases

Prognosis

The prognosis for individuals with Kabuki syndrome depends on the severity of symptoms and the presence of complications. With appropriate medical and developmental interventions, many individuals can achieve a good quality of life. Lifespan is often normal, although it can be affected by the severity of congenital anomalies and immune system dysfunction. Early intervention and ongoing support are essential to maximize developmental potential and manage health issues effectively.

Medical Disclaimer

The information provided on this page is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.