Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
Kabuki syndrome is a multi-system developmental disorder associated with intellectual disability of varying degrees (mild-severe), growth deficiency, typical facial features and structural anomalies such as congenital heart defects, cleft lip and/or palate, and kidney differences. There are currently two genes associated with Kabuki syndrome: KMT2D (formerly MLL2), and KDM6A. Heterozygous pathogenic variants in KMT2D are associated with the autosomal dominant form, whereas hemizygous and heterozygous pathogenic variants in KDM6A are associated with the X-linked form.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for comprehensive sequence and copy number analysis is dependent on the patient's clinical features. Pathogenic KMT2D variants are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases while the etiology of about 20% of cases remains unknown [Boniel 2021; PMID: 33805950].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first-degree relatives and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Synonyms
Kabuki, Kabuki make-up syndrome, lateral eversion of the lower lid, Niikawa-Kuroki Syndrome, KDM6A, KMT2D
KABUX
LIS Mnemonic
KABUX
Available STAT
Yes
Test Notes
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
There are currently two genes associated with Kabuki syndrome: KMT2D (formerly MLL2, Lysine-Specific Methyltransferase 2D on 12q13.12; OMIM# 147920) and KDM6A (Lysine-Specific Demethylase 6A on Xp11.3; OMIM# 300867). Alterations in KMT2D are heterozygous (autosomal dominant) and the vast majority arise de novo, whereas variants in KDM6A are X-linked, more often affecting males and can be seen as inherited variants from unaffected carrier females. This panel includes sequence and copy number analyses of the KMT2D and KDM6A genes.
CPT Codes
81479
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
Kabuki syndrome is a multi-system developmental disorder associated with intellectual disability of varying degrees (mild-severe), growth deficiency, typical facial features and structural anomalies such as congenital heart defects, cleft lip and/or palate, and kidney differences. There are currently two genes associated with Kabuki syndrome: KMT2D (formerly MLL2), and KDM6A. Heterozygous pathogenic variants in KMT2D are associated with the autosomal dominant form, whereas hemizygous and heterozygous pathogenic variants in KDM6A are associated with the X-linked form.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for comprehensive sequence and copy number analysis is dependent on the patient's clinical features. Pathogenic KMT2D variants are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases while the etiology of about 20% of cases remains unknown [Boniel 2021; PMID: 33805950].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first-degree relatives and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Synonyms
Kabuki, Kabuki make-up syndrome, lateral eversion of the lower lid, Niikawa-Kuroki Syndrome, KDM6A, KMT2D
KABUX
LIS Mnemonic
KABUX
Available STAT
Yes
Test Notes
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
There are currently two genes associated with Kabuki syndrome: KMT2D (formerly MLL2, Lysine-Specific Methyltransferase 2D on 12q13.12; OMIM# 147920) and KDM6A (Lysine-Specific Demethylase 6A on Xp11.3; OMIM# 300867). Alterations in KMT2D are heterozygous (autosomal dominant) and the vast majority arise de novo, whereas variants in KDM6A are X-linked, more often affecting males and can be seen as inherited variants from unaffected carrier females. This panel includes sequence and copy number analyses of the KMT2D and KDM6A genes.
