Test Code: 9437

Kabuki Syndrome: KMT2D and KDM6A Sequencing Panel
Test Code: 9437
Turnaround time: 5 weeks


Kabuki syndrome is a rare condition that affects multiple organ systems. It is characterized by five cardinal features: 1) characteristic facies; (2) skeletal anomalies; (3) dermatolyphic abnormalities; (4) mild-to-moderate intellectual disability; and (5) postnatal growth deficiency. Additional manifestations include a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, immunological defects, such as recurrent ear infections in infancy, and cardiac anomalies. The estimated prevalence is 1 in 32,000 with 400 cases reported worldwide. The majority of cases are de novo; however, parent-to-child transmission has been described.

Pathogenic variants in the KMT2D (formerly MLL2) (12q13.12) or KDM6A (Xp11.3) gene cause Kabuki syndrome. Ng et al. reports loss-of-function mutations in KMT2D in 9 of the 10 individuals in their discovery population with Kabuki syndrome. KMT2D-related Kabuki syndrome is inherited in an autosomal dominant manner. A small number of cases of Kabuki syndrome caused by pathogenic variants in KDM6A have been described. All pathogenic variants reported in the KDM6A gene have apparently been de novo; however, X-linked inheritance is possible.


  • GeneReviews
  • OMIM #147920: Kabuki Syndrome http://www.ncbi.nlm.nih.gov/omim/147920
  • Lederer et al. (2012). Am J Hum Genet, 90:119-124.
  • Miyake et al. (2013). Am J Med Genet Part A, 161A:2234-2243.
  • Ng et al. (2010). Nat Genet, 42(9): 790-794.


This test is indicated for:

  • Confirmation of a clinical diagnosis of Kabuki syndrome.
  • Carrier testing in adults with a family history of Kabuki syndrome.


PCR amplification of 54 and 29 exons contained in the KMT2D and KDM6A genes respectively is performed on the patient’s genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient’s gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.


Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%.


Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.


  • Sequencing and deletion/duplication analysis by CGH array of the KMT2D (formerly MLL2) and KDM6A genes individually is available.
  • Kabuki Syndrome: KMT2D and KDM6A Deletion/Duplication Panel.
  • Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.