Van der Woude Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
12081 GRHL3 81479,81479 Order Options and Pricing
IRF6 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
12081Genes x (2)81479 81479 $890 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

Van der Woude syndrome (VWS) is the most common form of syndromic orofacial cleft and is frequently associated with pathogenic variants in the IRF6 and GRHL3 genes. Although VWS is a highly penetrant disorder, expressivity is variable even within families. Individuals may present with lower-lip fistulae (pits), cleft lip, cleft palate, cleft uvula or a combination thereof (Angiero et al. 2018. PubMed ID: 29569458). Anodontia and hypodontia (partial anodontia) has also been reported (Lam et al. 2010. PubMed ID: 20415912). In addition, pathogenic variants in the IRF6 gene are reported to be associated with popliteal pterygium syndrome, a severe syndromic form of orofacial cleft accompanied by skin, genitourinary and skeletal features (Schutte et al. 2014. PubMed ID: 20301581).

Genetics

Pathogenic variants associated with VWS may be inherited in an autosomal dominant (AD) manner, or arise de novo (Peyrard-Janvid et al. 2005. PubMed ID: 16160700; Peyrard-Janvid et al. 2014. PubMed ID: 24360809). VWS is frequently associated with pathogenic missense variants, as well as loss-of-function and copy number variants in the IRF6 gene (Peyrard-Janvid et al. 2005. PubMed ID: 16160700; Manjegowda et al. 2014. PubMed ID: 25579819). IRF6 encodes the interferon regulatory factor 6 protein. This protein is a transcription factor that is expressed in the palatal shelves in the developing embryo (Kondo et al. 2002. PubMed ID: 12219090). This protein is also expressed in the hair follicles, palatal rugae, tooth germ and thyroglossal duct, external genitalia, and skin. Pathogenic missense variants associated with VWS typically localize to the conserved IRF6 winged-helix DNA-binding domain (exons 3 and 4) or the IRF6 SMIR/IAD protein-binding domain (exons 7 through 9), and result in haploinsufficency (Kondo et al. 2002. PubMed ID: 12219090).

Pathogenic variants in the GRHL3 gene are the second most frequent cause of VWS. Pathogenic missense and loss of function variants in GRHL3 are associated with VWS and orofacial cleft phenotypes (Peyrard-Janvid et al. 2014. PubMed ID: 24360809). To date, no pathogenic copy number variants have been reported in GRHL3. GRHL3 encodes the drosophila grainyhead (grh) protein. This protein is also a transcription factor that is expressed in the developing embryo (Ting et al. 2003. PubMed ID: 12549979).

Clinical Sensitivity - Sequencing with CNV PGxome

Approximately 70% of cases of Van der Woude syndrome (VWS) may be explained by pathogenic variants in the IRF6 gene (Desmyster et al. 2010. PubMed ID: 21045959). An additional 6% of cases of VWS may be explained by pathogenic variants in the GRHL3 gene (Peyrard-Janvid et al. 2014. PubMed ID: 24360809).

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 listed 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 testing include individuals with a personal or family history consistent with VWS, lower lip pits, or orofacial cleft.

Genes

Official Gene Symbol OMIM ID
GRHL3 608317
IRF6 607199
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
PGxome®
IRF6-Related Disorders via the IRF6 Gene
Van der Woude Syndrome (VWS) via the GRHL3 Gene

Citations

  • Angiero et al. 2018. PubMed ID: 29569458
  • Desmyter et al. 2010. PubMed ID: 21045959
  • Kondo et al. 2002. PubMed ID: 12219090
  • Lam et al. 2010. PubMed ID: 20415912
  • Manjegowda et al. 2014. PubMed ID: 25579819
  • Peyrard-Janvid et al. 2005. PubMed ID: 16160700
  • Peyrard-Janvid et al. 2014. PubMed ID: 24360809
  • Schutte et al. 2014. PubMed ID: 20301581
  • Ting et al. 2003. PubMed ID: 12549979

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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