KABUKI SYNDROME

Kabuki syndrome is characterized by a specific combination of external features, malformations, and developmental disorders. Typical features include elongated palpebral fissures, distinctive eyebrow and nose shapes, and certain hand and ear characteristics. Around 60% of cases are attributable to mutations in the KMT2D gene.

Symptoms

Kabuki syndrome is characterized by a combination of external features, malformations, and developmental disorders; failure to thrive in infancy and early childhood is often also seen. Characteristic craniofacial features include:

• Laterally elongated palpebral fissures with eversion of the lateral lower eyelid margin
• Arched, laterally sparse eyebrows, often with a hairless narrow area in the middle
• A short columella and flat-looking nasal tip
• Poorly shaped, large earlobes
• Persistent fetal fingertip pads
• Brachy-clinodactyly V
• Occasionally cleft palate or cleft lip and palate.

Initially, muscle hypotonia, pronounced failure to thrive requiring tube feeding, and a heart defect may be prominent, followed later by moderate developmental delay, frequent otitis and infections, and seizures in some patients.

Cause

Approximately 60% of Kabuki syndrome cases are caused by heterozygous pathogenic variants in the KMT2D gene, and rarely by pathogenic changes in KDM6A on the X chromosome. In some cases, no cause has been found to date, suggesting genetic heterogeneity.

References

Adam et al. 2019 J Med Genet 56:89 / Micale et al. 2011, Orphanet J Rare Dis 6:38 / Miyake et al. 2013, Am J Med Genet A 161A:2234 / Adam et al. 2011, GeneReviews "Kabuki syndrome"