Congenital Central Hypoventilation Syndrome (CCHS) via the PHOX2A 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
8965 PHOX2A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8965PHOX2A81479 81479(x2) $890 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 backbone).

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

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder that affects breathing (alveolar hypoventilation) and autonomic regulation. It often occurs in newborns and less frequently as a milder condition in young children and adults. Individuals affected with CCHS require assistance for breathing via a ventilator 24 hours a day or only during sleep. Tracheostomy along with assisted ventilation is especially recommended for young children (Weese-Mayer et al. 2014). Some individuals with CCHS also have associated Hirschsprung disease and/or neuroblastomas in up to 20% and 6% of cases, respectively. CCHS is also known as Ondine's curse and Haddad syndrome; the latter refers to the co-occurrence of CCHS and Hirschsprung disease (Lai and Schroer 2008), but these terms are not commonly used. The prevalence of CCHS is estimated at 1,000 individuals worldwide, but this may be an underestimate because individuals with a milder phenotype are underdiagnosed (Weese-Mayer et al. 2010).

Genetics

Congenital Central Hypoventilation Syndrome is inherited in an autosomal dominant manner and is usually caused by PHOX2B mutations. PHOX2A has also been associated with CCHS and HSCR, although its role is not totally clear. This gene is involved in early autonomic nervous system embryologic development and when mutated has been associated with the development of CCHS (Sasaki et al. 2003; Weese-Mayer et al. 2014). The PHOX2A protein product is involved in the development of the autonomic nervous system. It does so by regulating the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, and it has also been suggested that it is involved in the expression of RET (de Pontual 2003). In addition to CCHS, pathogenic variants in PHOX2A have also been associated with autosomal recessive congenital fibrosis of the extraocular muscles (Andrews et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity of mutations in this gene in CCHS is currently unknown due to the rarity of this disease.

Testing Strategy

This test provides full coverage of all coding exons of the PHOX2A 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

Individuals who are clinically suspected or diagnosed with CCHS. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PHOX2A.

Gene

Official Gene Symbol OMIM ID
PHOX2A 602753
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Congenital Central Hypoventilation Syndrome (CCHS) via the ASCL1 Gene
Congenital Central Hypoventilation Syndrome (CCHS) via the BMP2 Gene
Congenital Central Hypoventilation Syndrome (CCHS) via the PHOX2B Gene
Hereditary Neuroblastoma via the PHOX2B Gene
Hirschsprung Disease 3 (HSCR3) via the GDNF Gene
Hirschsprung Disease 4 (HSCR4) via the EDN3 Gene
Waardenburg Syndrome Type IVB via the EDN3 Gene

Citations

  • Andrews CV et al. 2011. Congenital Fibrosis of the Extraocular Muscles. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301522
  • de Pontual L. et al. 2003. Human molecular genetics. 12: 3173-80. PubMed ID: 14532329
  • Lai D., Schroer B. 2008. Journal of child neurology. 23: 341-3. PubMed ID: 18230845
  • Sasaki A, Kanai M, Kijima K, Akaba K, Hashimoto M, Hasegawa H, Otaki S, Koizumi T, Kusuda S, Ogawa Y, Tuchiya K, Yamamoto W, et al. 2003. Molecular analysis of congenital central hypoventilation syndrome. Human Genetics 114: 22–26. PubMed ID: 14566559
  • Weese-Mayer DE. et al. 2010. American journal of respiratory and critical care medicine. 181: 626-44. PubMed ID: 20208042
  • Weese-Mayer DE. et al. 2014. Congenital Central Hypoventilation Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301600

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.
  • 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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

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