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Waardenburg Syndrome Type IVA via the EDNRB Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
EDNRB 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11003EDNRB81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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


Genetic Counselors


  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Waardenburg syndrome (WS) is an auditory-pigmentary disorder characterized by congenital sensorineural hearing loss and pigmentary abnormalities of the hair, including a white forelock and pigmentary changes of the iris such as heterochromia. WS is classified into four main types depending on the clinical symptoms and is associated with causative mutations in several genes (Pingault et al. 2010; Read and Newton 1997).

WS I: Auditory-pigmentory abnormalities along with dystopia canthorum (lateral displacement of the inner canthi), caused by mutations in PAX3.
WS II: Auditory-pigmentory abnormalities without dystopia canthorum, caused by mutations in MITF, SNAI2 and SOX10.
WS III: Type I with musculo-skeletal abnormalities of the upper limb  (Klein-Waardenburg syndrome) caused by mutations in PAX3.
WS IV: Type II with Hirschsprung disease (Waardenburg-Shah syndrome), caused by mutations in EDNRB, EDN3 and SOX10.


WS type IVA is an autosomal recessive syndrome caused by mutations in EDNRB, which belongs to a family of genes called G protein-coupled receptors. EDNRB protein (endothelin receptor type B) is a cell surface protein and functions by interacting with endothelin 3 (EDN3). Endothelins are involved in the development and function of blood vessels, the production of certain hormones, and the stimulation of cell growth and division. Together EDNRB and EDN3 play a very important role in neural crest cells and pigment-producing cells called melanocytes. Disruption or loss of the EDNRB protein results in the loss of enteric nerve cells that are critical to intestinal development, resulting in Hirschsprung disease. Similarly, a lack of melanocytes due to loss of EDNRB protein also affects the coloring of skin, hair, and eyes and causes hearing loss, manifestations that are unique to Waardenburg syndrome. Rare cases of dominant transmission with incomplete penetrance have been reported.  

Mutations in EDNRB are also known to be causative for Hirschsprung disease and ABCD syndrome.

Clinical Sensitivity - Sequencing with CNV PGxome

EDNRB is one of the genes in which mutations are known to cause WSIVA. The clinical sensitivity of our sequencing assay for this gene is currently unknown. However, since mainly small deletions, missense and truncating mutations have been described for this gene associated with WSIVA, we believe that our sequencing assay will be able to identify a significant majority of the mutations.

Testing Strategy

This test provides full coverage of all coding exons of the EDNRB gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Diagnostic criteria for Waardenburg syndrome type IV (WSIV) includes the presence of Hirschsprung Disease along with any one of the criteria required for diagnosis of Waardenburg syndrome type II (WSII) as outlined (Liu et al. 1995), which includes congenital sensorineural hearing loss, complete heterochromia iridum (irides of different color) and absence of dystopia canthorum. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in EDNRB.


Official Gene Symbol OMIM ID
EDNRB 131244
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Hirschsprung Disease 2 (HSCR2) via the EDNRB Gene


  • Liu XZ, Newton VE, Read AP. 1995. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria. Am. J. Med. Genet. 55: 95100. PubMed ID: 7702105
  • Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. 2010. Review and update of mutations causing Waardenburg syndrome. Human Mutation 31: 391406. PubMed ID: 20127975


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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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