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.
- 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.
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.
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 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.
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
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
- 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.