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Hereditary Neuroblastoma via the PHOX2B Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8993 PHOX2B 81404 81404,81403 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8993PHOX2B81404 81404,81403 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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


  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Neuroblastoma is the most common type of childhood cancer that occurs before 1 year of age, accounting for 10-15% of cancer deaths in children. Approximately 90% of neuroblastomas are detected by 5 years of age, while 30% are found in the first year of life with the median age of diagnosis of 22 months (Esiashvili et al. Curr Probl Cancer 33:333-60, 2009). This tumor type can occur in adolescence and adulthood, although the prognosis is poorer compared to a childhood incidence (Colon and Chung. Advances in Pediatrics 58:297-311, 2011). The majority of neuroblastomas (65%) arise in the abdomen, with half of these in the medulla of the adrenal gland . They can also occur in the chest (20%), neck (5%), pelvis (5%), and 1% of cases have an unknown primary (Colon and Chung. Advances in Pediatrics 58:297-311, 2011). Symptoms of patients with neuroblastoma include malaise, fevers, weight loss, enlarging mass, pain, and abdominal distention. Other symptoms can include early-onset hypertension and tachycardia due to the secretion of catecholamines. Neuroblastomas commonly occur sporadically in a family, but 1-2% of cases occur with family histories of neuroblastoma. Hereditary neuroblastomas tend to have earlier presentations and lead to multiple primary cancers. They also show significant clinical heterogeneity, whereby a pedigree may show an individual with spontaneous cancer regression, whereas another individual with metastatic spread (Deyell and Attiyeh. Cancer Genetics 204:113-121, 2011). Siblings of an affected patient with neuroblastoma have a 10-fold increase in developing neuroblastoma (Friedman et al. Cancer Epidemiol Biomarkers Prev 14:1922-7, 2005). Neuroblastomas can also be found with other conditions such as Hirschsprung disease, congenital hypoventilation disorder, and neurofibromatosis type 1 (Johnson and Park. "ALK-Related Neuroblastoma Susceptibility." GeneReviews, 2012).


Hereditary neuroblastoma is an autosomal dominant disorder that shows incomplete penetrance (Fisher and Tweddle. Seminars in Fetal & Neonatal Medicine 17: 207-215, 2012). Neuroblastomas show whole-chromosome gains and segmental chromosomal aberrations. The former results from hyperdiploidy and has a favorable prognosis, whereas the latter is associated with MYCN amplification and associated with worse outcomes (Colon and Chung. Advances in Pediatrics 58:297-311, 2011). The most frequent genetic aberration is an unbalanced chromosome 17q gain found in 70% of neuroblastomas, which has a poor prognosis (Bown et al. N Engl J Med 340:1954-1961, 1999). In cases of hereditary neuroblastoma the most common etiology are mutations in the anaplastic lymphoma kinase (ALK) oncogene. Another less frequent cause of hereditary neuroblastomas are from PHOX2B mutations, which are often associated with Hirschsprung's disease and/or congenital hypoventilation (Mosse et al. Am J Hum Genet 75:727-730, 2004). PHOX2B encodes a transcription factor that is involved in the normal sympathetic neuronal development and catecholamine synthesis. PHOX2B mutations are rarely found in sporadic neuroblastomas (van Limpt et al. Oncogene 23:9280-8, 2004). The majority of causative PHOX2B mutations include missense and small insertions and deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Taken together, ALK and PHOX2B germline mutations account for 90% of hereditary neuroblastoma, with the majority being in the ALK gene (Fisher and Tweddle. Seminars in Fetal & Neonatal Medicine 17: 207-215, 2012).

Testing Strategy

This test provides full coverage of all coding exons of the PHOX2B gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Hereditary neuroblastoma should be suspected in neonates where there is a family history of neuroblastoma in two or more 1st degree relatives. Genetic testing for PHOX2B mutations should especially be carried out for individuals with neuroblastomas associated with Hirschsprung's disease and/or congenital hypoventilation (Mosse et al. Am J Hum Genet 75:727, 2004). Persons with PHOX2B germline mutations may also have dysmorphic features, including downslanting palpebral fissures, small nose, triangular shaped mouth, or low-set, posteriorly rotated ears (Johnson and Park. GeneReviews. 2012). This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
PHOX2B 603851
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Neuroblastoma 2 AD 613013

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Congenital Central Hypoventilation Syndrome (CCHS) via the PHOX2B Gene
Hereditary Neuroblastoma via the ALK Gene
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Hirschsprung Disease 3 (HSCR3) via the GDNF Gene
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  • Bown et al. (1999). "Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma." N Engl J Med 340:1954-1961. PubMed ID: 10379019
  • Colon and Chung. (2011). "Neuroblastoma." Advances in Pediatrics 58:297-311. PubMed ID: 21736987
  • Deyell and Attiyeh. (2011). "Advances in the understanding of constitutional and somatic genomic alterations in neuroblastoma." Cancer Genetics 204:113-121. PubMed ID: 21504710
  • Esiashvili et al. (2009) "Neuroblastoma." Curr Probl Cancer 33:333-60. PubMed ID: 20172369
  • Fisher and Tweddle. (2012). "Neonatal neuroblastoma." Seminars in Fetal & Neonatal Medicine 17: 207-215. PubMed ID: 22673527
  • Friedman et al. (2005). "Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study." Cancer Epidemiol Biomarkers Prev 14:1922-7. PubMed ID: 16103438
  • Human Gene Mutation Database.
  • Johnson and Park. (2012). "ALK-Related Neuroblastoma Susceptibility." GeneReviews. PubMed ID: 20301782
  • Mosse et al. (2004). "Germline PHOX2B mutation in hereditary neuroblastoma." Am J Hum Genet 75:727-730. PubMed ID: 15338462
  • van Limpt et al. (2004). "The Phox2B homeobox gene is mutated in sporadic neuroblastomas." Oncogene 23:9280-8. PubMed ID: 15516980


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

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