Feingold Syndrome 1 via the MYCN 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
12681 MYCN 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12681MYCN81479 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.

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

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Feingold syndrome 1 (FS1), also known as oculo-digito-esophageal-duodenal syndrome or ODED syndrome, is a rare congenital disorder typically characterized by brachymesophalangy (short middle phalanx of finger), toe syndactyly, microcephaly, short palpebral fissures, mild learning deficits, and short stature (less than tenth percentile). Minor features of FS1 include thumb hypoplasia, micrognathia, renal abnormalities, cardiac abnormalities and hearing loss. Some patients have also demonstrated atresia of the esophagus, duodenum, jejunum, and/or anus (Celli et al. 2003. PubMed ID: 14518066). Currently, the incidence of FS1 is unknown as reports are limited to case reports and small familial studies, but is estimated to be very rare (less than 1 in 1,000,000). The genetic cause of FS1 was mapped to chromosome 2p23-24 (Celli et al. 2003. PubMed ID: 14518066), and eventually MYCN was identified as the causative gene (van Bokhoven et al. 2005. PubMed ID: 15821734).

Genetic testing for FS1 through MYCN analysis can be used to molecularly confirm a clinical diagnosis, inform reproductive decision making in families with known or suspected cases of FS1, and identify de novo variants in known or suspected FS1 cases.

Genetics

FS1 is inherited in an autosomal dominant manner through pathogenic variants in MYCN. FS1 appears to have complete penetrance with variable expressivity, even within families (Blaumeiser et al. 2008. PubMed ID: 18671284). A very similar disorder with the same phenotype presentation with the exception of gastrointestinal anomalies, known as Feingold syndrome 2, is caused by pathogenic variants in MIR17HG.

Reported pathogenic variants in MYCN include missense, nonsense, small frameshift deletions, small framshift insertions/duplications, and gross deletions. The majority of affected individuals have small pathogenic variants within the MYCN sequence, and there are no significant differences in clinical presentation reported amongst these individuals. Large deletions of chromosome 2p, including MYCN as well as surrounding genes, typically present as FS1 with additional clinical features (Burnside et al. 2018. PubMed ID: 30088856).

The MYCN protein is a nuclear transcription factor implicated in developmental processes. Thus, variants in the helix-loop-helix (HLH) domain, which is crucial for DNA binding, and nonsense variants that occur upstream of the HLH domain, are often found to be pathogenic (Blaumeiser et al. 2008. PubMed ID: 18671284; van Bokhoven et al. 2005. PubMed ID: 15821734). The majority of pathogenic variants reported in MYCN are present in exon 3, but a small proportion of variants have also been reported in exon 2 (Blaumeiser et al. 2008. PubMed ID: 18671284; Cognet et al. 2011. PubMed ID: 21224895; Marcelis et al. 2008. PubMed ID: 18470948).

Although the bulk of reported FS1 cases with MYCN variants are familial, de novo variants have also been reported (Blaumeiser et al. 2008. PubMed ID: 18671284; Cognet et al. 2011. PubMed ID: 21224895; Marcelis et al. 2008. PubMed ID: 18470948; Yu et al. 2018. PubMed ID: 29786759).

Several mouse models for FS1 and MYCN loss have been created. Conditional knockout of Mycn in myocardial tissue results in thin myocardial walls (Harmelink et al. 2013. PubMed ID: 23063798) and conditional knockout of Mycn in developing limbs results in severe brachysyndactyly (Mirzamohammadi et al. 2018. PubMed ID: 29636449), similar to that observed in FS1 patients. Homozygous deletion of Mycn results in embryonic lethality approximately half way through mouse gestation (Charron et al. 1992. PubMed ID: 1459450).

Clinical Sensitivity - Sequencing with CNV PGxome

This test has an estimated clinical sensitivity of 68% for detecting Feingold syndrome 1 in patients that display clinical features associated with FS1 (Blaumeiser et al. 2008. PubMed ID: 18671284; Cognet et al. 2011. PubMed ID: 21224895; Marcelis et al. 2008. PubMed ID: 18470948; van Bokhoven et al. 2005. PubMed ID: 15821734). The remaining individuals frequently are diagnosed with syndromes with significant phenotypic overlap, including Feingold syndrome 2, CHARGE syndrome, Fanconi Anemia, and VACTERL association (Marcelis et al. 2019. PubMed ID: 20301770).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the MYCN gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to 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

Candidates for this test include individuals with a family history of FS1 and/or the presence of phenotypes associated with FS1, including: digital anomalies (brachymesophalangy, thumb hypoplasia, toe syndactyly), microcephaly, short palpebral fissures, and/or gastrointestinal atresias diagnosed pre- or postnatally by imaging studies (ultrasound or MRI). Targeted testing is indicated for family members of patients who have a known pathogenic variant in MYCN.

Gene

Official Gene Symbol OMIM ID
MYCN 164840
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Feingold Syndrome 1 AD 164280

Citations

  • Blaumeiser et al. 2008. PubMed ID: 18671284
  • Burnside et al. 2018. PubMed ID: 30088856
  • Celli et al. 2003. PubMed ID: 14518066
  • Charron et al. 1992. PubMed ID: 1459450
  • Cognet et al. 2011. PubMed ID: 21224895
  • Harmelink et al. 2013. PubMed ID: 23063798
  • Marcelis et al. 2008. PubMed ID: 18470948
  • Marcelis et al. 2019. PubMed ID: 20301770
  • Mirzamohammadi et al. 2018. PubMed ID: 29636449
  • van Bokhoven et al. 2005. PubMed ID: 15821734
  • Yu et al. 2018. PubMed ID: 29786759

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×