Kabuki syndrome

Kabuki syndrome (also known as Kabuki make-up syndrome or Niikawa-Kuroki syndrome) is a rare multisystem congenital disorder characterized by a distinctive facial appearance, skeletal anomalies, intellectual disability, and growth deficiency. The name derives from the resemblance of affected individuals' facial features to the stage makeup used in traditional Japanese Kabuki theater. The condition was first described independently by Niikawa and Kuroki in 1981. Kabuki syndrome is caused primarily by mutations in the KMT2D gene (formerly MLL2) on chromosome 12, accounting for approximately 55-80% of cases (Kabuki syndrome type 1), or less commonly by mutations in the KDM6A gene on the X chromosome (Kabuki syndrome type 2), accounting for approximately 5-8% of cases. Both genes encode chromatin-modifying enzymes involved in epigenetic regulation of gene expression. The hallmark facial features include long palpebral fissures with eversion of the lateral third of the lower eyelid, arched eyebrows with sparseness or notching of the lateral third, a broad and depressed nasal tip, and prominent or cupped ears. Skeletal abnormalities frequently include brachydactyly (short fingers), clinodactyly of the fifth finger, vertebral anomalies, and joint hypermobility. Intellectual disability ranges from mild to moderate in most patients, though some individuals have borderline or normal intelligence. Additional features commonly include postnatal growth deficiency, congenital heart defects (present in 30-55% of patients, most commonly coarctation of the aorta and septal defects), renal and urinary tract anomalies, hearing loss, recurrent infections related to immune deficiency, and persistent fetal fingertip pads. Feeding difficulties are common in infancy, and premature breast development (thelarche) may occur in females. There is currently no cure for Kabuki syndrome, and management is supportive and multidisciplinary. Treatment focuses on addressing specific manifestations: surgical correction of cardiac or palatal defects, growth hormone therapy for growth deficiency (which has shown benefit in some patients), early intervention programs and special education for developmental delays, speech therapy, immunoglobulin replacement for significant immune deficiency, and regular monitoring of hearing and vision. Patients benefit from coordinated care involving genetics, cardiology, immunology, endocrinology, and developmental specialists. With appropriate support, many individuals with Kabuki syndrome can achieve meaningful developmental progress and a good quality of life.

Common questions about Kabuki syndrome