Kabuki Syndrome: KMT2D Gene Deletion/Duplication

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Condition Description

Kabuki syndrome is a rare condition that affects multiple organ systems.  It is characterized by 5 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. 

Mutations in KMT2D, also known as MLL2, can cause Kabuki syndrome.  Ng et al. reports loss-of-function mutations in 9 of the 10 individuals in their discovery population with Kabuki syndrome.

For patients with suspected Kabuki syndrome, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

Visit www.ThinkGenetic.com for patient-friendly information on Kabuki syndrome.

References:

  • OMIM #147920: Kabuki Syndrome
  • Ng et al. (2010). Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet, 42(9): 790-794.

Genes (2)

KMT2D, MLL2
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Indications

This test is indicated for:

  • Confirmation of a clinical diagnosis of Kabuki syndrome in an individual in whom sequence analysis was negative.
  • Carrier testing in adults with a family history of Kabuki syndrome in whom sequence analysis was negative.

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.



Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.

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

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

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

Special Instructions

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition.

  • Sequence analysis of the KMT2D gene is available and is required before deletion/duplication analysis.  
  • 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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