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Waardenburg Syndrome Types I and III via the PAX3 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
PAX3 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8613PAX381479 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 4 main types depending on the clinical symptoms and has causative mutations in different genes (Pingault et al., 2010).

WS I : Auditory-pigmentary abnormalities along with dystopia canthorum (lateral displacement of the inner canthi), caused by mutations in PAX3.

WS II : Auditory-pigmentary 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 EDN3, EDNRB, and SOX10.

WS I: The hearing loss observed in approximately 60% of affected individuals is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs (Milunsky et al, Gene Reviews). WS III: The musculo-skeletal abnormalities present with flexion contractures and muscle hypoplasia of the upper limb with a broad range of severity. Other signs such as campylodactly may be associated.


WS type 1 is an autosomal dominant syndrome caused by heterozygous mutations in PAX3, while WS type 3 can be caused by heterozygous or homozygous mutations in PAX3 suggesting an autosomal dominant or recessive mode of inheritance. PAX3 belongs to a family of homeobox transcription factor genes that play a critical role in the formation of tissues and organs during embryonic development. The PAX3 protein directs the activity of other genes that signal neural crest cells to form specialized tissues or cell types such as some nerve tissue, bones in the face and skull (craniofacial bones), and pigment-producing cells called melanocytes. Disruption or loss of the PAX3 protein results in the manifestation of the limb and facial features that are unique to Waardenburg syndrome, types I and III. Mutations in PAX3 are also known to be causative for craniofacial-deafness-hand syndrome. The types of causative mutations reported in PAX3 include missense, nonsense, splicing, and inframe deletions.

Clinical Sensitivity - Sequencing with CNV PGxome

PAX3 is the only gene in which mutations are known to cause WS type 1 and type 3; molecular genetic testing by sequencing of PAX3 detects more than 90% of disease-causing mutations.

Molecular genetic testing by deletion/duplication analysis of PAX3 detects about 6% of disease-causing mutations.

Testing Strategy

This test provides full coverage of all coding exons of the PAX3 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 has been proposed by the Waardenburg Consortium (Farrer et al., 1992). An individual must have two major criteria or one major plus two minor criteria to be considered affected. Major Criteria:

Congenital sensorineural hearing loss White forelock, hair hypopigmentation Pigmentation abnormality of the iris: Complete heterochromia iridum (irides of different color), Partial/segmental heterochromia (two different colors in same iris, typically brown and blue), Hypoplastic blue irides, or brilliant blue irides Dystopia canthorum, W index >1.95 Affected first-degree relative.

Minor Criteria

Skin hypopigmentation (congenital leukoderma), Synophrys/medial eyebrow flare, Broad/high nasal root, prominent columella, Hypoplastic alae nasi, Premature gray hair (age of < 30 years).

This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PAX3.


Official Gene Symbol OMIM ID
PAX3 606597
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Waardenburg Syndrome Panel


  • Farrer LA, Grundfast KM, Amos J, Arnos KS, Asher JH, Beighton P, Diehl SR, Fex J, Foy C, Friedman TB, Greenberg J, Hoth C, et al. 1992. Waardenberg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS consortium. Am J Hum Genet 50: 902913. PubMed ID: 1349198
  • Milunsky JM. 2011. Waardenburg Syndrome Type I. GeneReviews. PubMed ID: 20301703
  • 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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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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