Kabuki Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10173 ANKRD11 81479,81479 Order Options and Pricing
BCO1 81479,81479
HNRNPK 81479,81479
KDM1A 81479,81479
KDM6A 81479,81479
KMT2D 81479,81479
OTUD6B 81479,81479
RAP1A 81479,81479
RAP1B 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10173Genes x (9)81479 81479 $1070 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Kabuki syndrome (KS) is a multiple congenital disorder characterized by arched and broad eyebrows, long palpebral fissures with the everted lateral third of the lower eye lids, depressed nasal tip, large protruding earlobes, persistence of fetal fingertip pads, skeletal defects, developmental delay and mental retardation. Other features include congenital heart defects, genitourinary anomalies, cleft lip and/or palate, gastrointestinal anomalies hearing loss, and widely spaced teeth and hypodontia. Patients may also have frequent infections, seizures, and feeding problems (Miyake et al. 2013. PubMed ID: 23913813; Adam et al. 2019 PubMed ID: 21882399).

Genetics

Kabuki syndrome can be autosomal dominant (caused by pathogenic variants in KMT2D/MLL2) or X-linked dominant (caused by pathogenic variants in KDM6A). The KMT2D protein coded by exons 1 to 54 of the KMT2D gene on 12q12-q14 is a histone methyltransferase that methylates the Lys-4 position of histone H3. The KDM6A protein coded by exons 1 to 29 of the KDM6A gene on Xp11.2 is a histone demethylase that specifically demethylates the Lys-27 position of histone H3. Pathogenic variants in KMT2D and KDM6A account for approximately 2/3 and 1/3 of pathogenic variants identified in Kabuki patients, respectively (Micale et al. 2014. PubMed ID: 24633898).

To date, more than 400 unique pathogenic variants in KMT2D have been documented. They are missense (20%), nonsense (30%), splicing (8%), small del/ins (40%), and ~2% large deletions and duplications. The majority of pathogenic variants occur de novo (Micale et al. 2014. PubMed ID: 24633898; Banka et al. 2013. PubMed ID: 22901312; Human Gene Mutation Database).

Pathogenic variants in KDM6A cause X-linked dominant Kabuki syndrome. To date, more than 30 unique pathogenic variants have been documented and include missense (6%), nonsense (17%), splicing (11%), small deletions (20%), large deletions/duplications and complex large rearrangements (46% ) (Lindgren et al. 2013. PubMed ID: 23354975; Micale et al. 2014. PubMed ID: 24633898; Banka et al. 2013. PubMed ID: 22901312; Human Gene Mutation Database).

Recently, an apparently homozygous undocumented missense RAP1A variant (c.488G>C, p.Arg163Thr) was found in one KS patient due to paternal uniparental isodisomy, and a de novo undocumented missense RAP1B variant (c.451A>G, p.Lys151Glu) was found in one KS patient (Bögershausen et al. 2015. PubMed ID: 26280580). RAP1A and RAP1B are members of the Ras family of small GTPases that function in early tissue/organ development.

Pathogenic variants in ANKRD11, KDM1A, BCO1, HNRNPK , and OTUD6B have been reported in a few cases with Kabuki-like syndrome or patients with mild intellectual disability associated with seizures and dysmorphic features (Tunovic et al. 2014. PubMed ID: 24838796; Gambin et al. 2017. PubMed ID: 27980096; Kernohan et al. 2018. PubMed ID: 30160830; Santiago-Sim et al. 2017. PubMed ID: 28343629).

Clinical Sensitivity - Sequencing with CNV PGxome

In two cohort studies with 303 and 81 clinically diagnosed Kabuki patients, KMT2D pathogenic variants were found in 43% and 61% of the studied patients, while KDM6A pathogenic variants were identified in 1% and 6% of the studied patients (Miyake et al. 2013. PubMed ID: 23913813; Micale et al. 2014. PubMed ID: 24633898). RAP1A and RAP1B pathogenic variants account for only rare cases (Bögershausen et al. 2015. PubMed ID: 26280580).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients who have symptoms consistent with Kabuki syndrome.

Genes

Official Gene Symbol OMIM ID
ANKRD11 611192
BCO1 605748
HNRNPK 600712
KDM1A 609132
KDM6A 300128
KMT2D 602113
OTUD6B 612021
RAP1A 179520
RAP1B 179530
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Adam et al. 2019 PubMed ID: 21882399
  • Banka et al. 2013. PubMed ID: 22901312
  • Bögershausen et al. 2015. PubMed ID: 26280580
  • Gambin et al. 2017. PubMed ID: 27980096
  • Human Gene Mutation Database (Bio-base).
  • Kernohan et al. 2018. PubMed ID: 30160830
  • Lindgren et al. 2013. PubMed ID: 23354975
  • Micale et al. 2014. PubMed ID: 24633898
  • Miyake et al. 2013. PubMed ID: 23913813
  • Santiago-Sim et al. 2017. PubMed ID: 28343629
  • Tunovic et al. 2014. PubMed ID: 24838796

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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