Kabuki Syndrome

Kabuki syndrome (KS) is a rare, multisystem congenital disorder characterized by distinctive facial features, growth deficiency, varying degrees of intellectual disability, skeletal abnormalities, and visceral malformations.

Key Points

• Prevalence: 1:32,000 births
• First described in 1981 by Japanese scientists Niikawa and Kuroki
• Named due to facial resemblance to makeup worn in Kabuki theater
• Also known as Niikawa-Kuroki syndrome

Cardinal Features (5 Main Manifestations)

• Characteristic Facial Features:
  • Elongated palpebral fissures with eversion of lateral third of lower eyelid
  • Arched and broad eyebrows with lateral sparseness
  • Short columella with depressed nasal tip
  • Large, prominent, or cupped ears
  • High/cleft palate
• Skeletal Anomalies:
  • Short stature
  • Scoliosis
  • Brachydactyly
  • Clinodactyly of fifth digits
  • Hip dislocation
• Dermatoglyphic Abnormalities:
  • Persistent fetal fingertip pads
  • Increased digital ulnar loops
• Intellectual Disability:
  • Mild to moderate in 87% of cases
  • Speech delay
  • Motor developmental delay
• Postnatal Growth Deficiency:
  • Short stature
  • Failure to thrive
  • Feeding difficulties in infancy

Associated Features

• Cardiac Anomalies (40-50%):
  • Septal defects
  • Coarctation of aorta
  • Tetralogy of Fallot
• Genitourinary Abnormalities:
  • Cryptorchidism
  • Kidney/urinary tract malformations
• Immunological Issues:
  • Frequent infections
  • Hypogammaglobulinemia
  • Autoimmune disorders
• Endocrine Abnormalities:
  • Premature thelarche
  • Growth hormone deficiency

Genetic Basis

• Primary Genes Involved:
  • KMT2D (formerly MLL2) - 56-75% of cases
    • Located on chromosome 12q13.12
    • Autosomal dominant inheritance
    • Histone methyltransferase function
  • KDM6A - 5-8% of cases
    • Located on Xp11.3
    • X-linked dominant inheritance
    • Histone demethylase function
• Molecular Mechanisms:
  • Both genes involved in epigenetic regulation
  • Affect chromatin remodeling
  • Impact developmental gene expression

Multidisciplinary Approach

• Initial Evaluation:
  • Comprehensive genetic evaluation
  • Cardiac assessment
  • Developmental assessment
  • Growth monitoring
  • Immunological screening
• Ongoing Care:
  • Regular developmental monitoring
  • Speech and language therapy
  • Physical therapy
  • Occupational therapy
  • Regular dental care
• Medical Management:
  • Cardiac follow-up if anomalies present
  • Immunological support if needed
  • Growth hormone therapy if indicated
  • Treatment of feeding difficulties
  • Management of skeletal issues

Long-term Outcomes

• Life Expectancy:
  • Generally normal if no severe complications
  • Depends on associated anomalies
• Quality of Life:
  • Variable depending on severity
  • Most achieve some degree of independence
  • Early intervention improves outcomes