Adams-Oliver Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
13027 ARHGAP31 81479,81479 Order Options and Pricing
DLL4 81479,81479
DOCK6 81479,81479
EOGT 81479,81479
KCTD1 81479,81479
MYH9 81479,81479
NOTCH1 81407,81479
RBPJ 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
13027Genes x (8)81479 81407, 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

Adams-Oliver syndrome (AOS) is a congenital condition characterized mainly by aplasia cutis congenita and limb defects with an estimated incidence of 1 in 225,000 live births (Saeidi and Ehsanipoor. 2017. PubMed ID: 29387678). The clinical features include congenital missing skin typically on the top of the skull, tapering fingers, and hyperplastic distal phalanges of the hands and feet. Some patients may have heart problems, including ventricular septal defect and patent ductus arteriosus (Shaheen et al. 2013. PubMed ID: 23522784; Hassed et al. 2012. PubMed ID: 22883147; Lehman et al. 2016. PubMed ID: 27077170; Meester et al. 2018. PubMed ID: 29924900). Pathogenic variants in KCTD1 are associated with Scalp-Ear-Nipple (SEN) syndrome, which is characterized by cutis aplasia of the scalp; minor defects of the external ears, digits, and nails; and malformed breast (Marneros et al. 2013. PubMed ID: 23541344). Molecular genetic testing is advantageous to establish an accurate diagnosis for individuals with Adams-Oliver syndrome or related conditions.

Genetics

Pathogenic variants in ARHGAP31DLL4NOTCH1RBPJ, and MYH9 cause autosomal dominant AOS, while pathogenic variants in DOCK6 and EOGT cause autosomal recessive Adams-Oliver syndrome (Shaheen et al. 2013. PubMed ID: 23522784; Hassed et al. 2012. PubMed ID: 22883147; Isrie et al. 2014. PubMed ID: 24668619; Uyeda et al. 2012. PubMed ID: 22631568; Lehman et al. 2016. PubMed ID: 27077170). This panel includes genes known to cause Adams-Oliver syndrome, as well as KCTD1, which is involved in autosomal dominant scalp-ear-nipple syndrome (Marneros et al. 2013. PubMed ID: 23541344). 

The DOCK6 and ARHGAP31 proteins are GTPase-accelerating proteins (GAP) and serve as switches between inactive GDP-bound and active GTP-bound, particularly during development of the limbs, skull, and heart (Southgate et al. 2011. PubMed ID: 21565291). The DLL4, NOTCH1, RBPJ, and EOGT proteins are involved in the NOTCH signal pathway which regulates cell-fate determination during development and maintains adult tissue homeostasis (Hori et al. 2013. PubMed ID: 23729744). The types of pathogenic variants reported include missense, nonsense, splicing, small deletion/insertion, large deletion/insertion, regulatory and complex rearrangment (Human Gene Mutation Database).

In the following table are the shown the fraction of AOS cases that are explained by pathogenic variants in the indicated genes.

Gene % of AOS
ARHGAP31 <5% 
DLL4 ~10% 
DOCK6 ~17% 
EOGT <10% 
NOTCH1 ~23% 
RBPJ <10%

Table from Lehman et al. 2016.

At least one de novo MYH9 pathogenic variant was reported in one patient with congenital scalp hemangioma (Fomchenko. 2018. PubMed ID: 29903892).

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants were found in 36%-50% of Adams-Oliver syndrome cases (Lehman et al. 2016. PubMed ID: 27077170; Meester et al. 2018. PubMed ID: 29924900). Large deletions or duplications were reported in NOTCH1, RBPJ, and DOCK6 (Westphal. 2019. PubMed ID: 30868567; Liang et al. 2016. PubMed ID: 28030855; Sukalo et al. 2015. PubMed ID: 25824905; Human Gene Mutation Database).

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 with symptoms consistent with Adams-Oliver syndrome and Scalp-Ear-Nipple syndrome.  

Genes

Official Gene Symbol OMIM ID
ARHGAP31 610911
DLL4 605185
DOCK6 614194
EOGT 614789
KCTD1 613420
MYH9 160775
NOTCH1 190198
RBPJ 147183
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Fomchenko. 2018. PubMed ID: 29903892
  • Hassed et al. 2012. PubMed ID: 22883147
  • Hori et al. 2013. PubMed ID: 23729744
  • Human Gene Mutation Database (Biobase).
  • Isrie et al. 2014. PubMed ID: 24668619
  • Lehman et al. 2016. PubMed ID: 27077170
  • Liang et al. 2016. PubMed ID: 28030855
  • Marneros et al. 2013. PubMed ID: 23541344
  • Meester et al. 2018. PubMed ID: 29924900
  • Saeidi and Ehsanipoor. 2017. PubMed ID: 29387678
  • Shaheen et al. 2013. PubMed ID: 23522784
  • Southgate et al. 2011. PubMed ID: 21565291
  • Southgate et al. 2011. PubMed ID: 21565291
  • Sukalo et al. 2015. PubMed ID: 25824905
  • Uyeda et al. 2012. PubMed ID: 22631568
  • Westphal. 2019. PubMed ID: 30868567

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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