Kabuki Syndrome (KMT2D) Sequencing

Confirm diagnosis of KS

Useful when a pathogenic familial variant identifiable by sequencing is known

Kabuki syndrome (KS) is a genetic disorder that results in particular dysmorphic facial features and often includes developmental delay or intellectual disability. Pathogenic variants in the KMT2D gene are the most common etiology, accounting for about 56-75% of cases. Causative variants in the KDM6A gene have also been reported.  In approximately 30% of individuals, the genetic cause cannot be determined. 

Disease Overview


  • In Japan: ~1:32,000 
  • In other ethnic groups: likely similar to that of the Japanese population 


New Zealand and Australian populations: 1:86,000 

Diagnostic Criteria

A definitive diagnosis of KS requires :

  • Developmental delay and/or intellectual disability
  • Infantile hypotonia
  • One or both of the following:
    • Pathogenic variant of KMT2D or KDM6A
    • Dysmorphic features
      • Arched eyebrows with sparse lateral third, long palpebral fissures with eversion of the lower eyelid
      • Flat nasal tip
      • Large dysplastic ears
      • Persistent fingertip pads



KMT2D (previously known as MLL2) 


Autosomal dominant 

Pathogenic Variants

  • Over 400 pathogenic KMT2D variants have been reported, including :
    • Nonsense mutations
    • Small deletions
    • Small insertions or duplications
    • Missense variants
    • Splice-site variants
    • Several large deletions/insertions (not detected by KMT2D sequencing)
  • Percentage of de novo variants is unknown but likely high 

Test Interpretation


  • Clinical sensitivity: ~75% 
  • Analytical sensitivity/specificity: 99% 


Results Result Description Interpretive Data


One pathogenic variant detected in KMT2D gene

Confirms diagnosis and etiology


No pathogenic variant detected in KMT2D gene

Diagnosis of KS less likely but not excluded


Variant(s) of unknown clinical significance identified



  • Large deletions/duplications, deep intronic pathogenic variants and some regulatory region variants will not be detected
  • KDM6A pathogenic variants or variants in other yet undiscovered genes associated with KS will not be detected
  • Germline or somatic mosaicism will not be detected
  • Diagnostic errors can occur due to rare sequence variations


  1. GeneReviews - Kabuki Syndrome

    Adam MP, Hudgins L, Hannibal M. Kabuki syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2020. [Last Revision: Oct2019; Accessed: Feb 2020]