Introduction
- Definition: A rare developmental disorder characterized by:
- Developmental delay
- Hypotonia
- Distinctive facial dysmorphism (elongated palpebral fissures, arched eyebrows, depressed nasal tip, thickened lower lip, prominent ears)
- Growth retardation
- Multisystem involvement (cardiac, gastrointestinal, renal, immunological)
Molecular Genetics
- Estimated prevalence: 1 in 32,000
- Initially thought to be specific to East Asians, but occurs across ethnicities
Clinical Features by System
A. Growth & Endocrinology
- KMT2D mutations (75% of cases, autosomal dominant)
- KDM6A mutations (5%, X-linked dominant)
- Unknown etiology in ~20% of cases
A child exhibiting cardinal Kabuki syndrome facial dysmorphism: long palpebral fissures with eversion of the lateral third of the lower eyelid; wide, arched eyebrows with sparseness or lack of the lateral third; short columella (lower part of the nasal septum) with depressed nasal tip; large, prominent or cup-shaped ears; persistent fetal finger pads. (source: Genes (Basel). 2021 Mar 25;12(4):468. doi: 10.3390/genes12040468) B. Neurological Issues
- KMT2D (MLL2):
- Histone methyltransferase (H3K4 methylation → chromatin opening → gene activation)
- Regulates cell differentiation (neural crest, cardiac, skeletal development)
- Loss-of-function mutations → impaired enhancer activation
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