Kabuki Syndrome: KMT2D and KDM6A Deletion/Duplication Panel

Condition Description

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.  

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References:

  • 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.

Genes (2)

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Indications

This test is indicated for:

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

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient\'s clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
  • Sequencing and deletion/duplication analysis by CGH array of the KMT2D (formerly MLL2) and KDM6A genes individually is available.
  • Kabuki Syndrome: KMT2D and KDM6A Sequencing Panel.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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