Infantile Myofibromatosis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10091 NOTCH3 81406,81479 Order Options and Pricing
PDGFRB 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10091Genes x (2)81479 81406, 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

Infantile myofibromatosis (IM), previously known as congenital generalized fibromatosis, is characterized by the development of tumors in various tissues and organs. IM affects mostly infants and young children. Although tumors are usually detected at birth or during the first two years of life, adult onset has been also reported (Chung and Enzinger 1981).

Two main types of IM, solitary and multicentric, are distinguished. Each type is further divided in two groups based on the presence or absence of visceral involvement (Wiswell et al. 1988).

The solitary type is characterized by the development of a single nodule mainly in the bones, striated muscle, skin, or subcutaneous tissues. In rare cases, solitary tumors have been reported in the viscera.

The multicentric type is characterized by the development of multiple nodules in various organs. Visceral involvement is common in this type. The lungs, heart, gastrointestinal tract, pancreas, liver, and bones are most commonly affected. Involvement of the central nervous system appears to be rare (Wada et al. 1998). IM with visceral involvement has a poor prognosis, although spontaneous regression has been reported in some cases (Teng et al. 1963).

About half the patients with IM have the solitary type and the other half have the multicentric type. The solitary type affects older individuals in about 20% of patients. Both solitary and multicentric IM have a good prognosis in the absence of visceral involvement when the tumors regress spontaneously during the first years of life. However, new tumors may develop later.

IM is clinically heterogeneous. Symptoms are highly variable and depend on the number and location of tumors. The disease may be limited to the skin in some patients, while several visceral organs are involved in other patients. Affected related members may present either with the solitary type with no visceral involvement or the multicentric visceral type (Cheung et al. 2013). The tumors consist of soft tissues abnormalities, and are usually benign. However, complications may occur when the tumors affect the normal function of vital organs such as the brain or viscera.

Although rare, IM has been reported in various ethnic and geographical groups (Cheung et al. 2013).

Genetics

In most of the IM-affected families reported, the disease is inherited in an autosomal dominant manner. In rare families, a recessive mode of transmission is speculated. It has been argued that family history may be difficult to obtain due to the spontaneous regression of tumors (Narchi 2001).

Autosomal Dominant IM is genetically heterogeneous. Two genes, PDGFRB and NOTCH3, have been implicated in the disease.

Two germline pathogenic missense variants in the PDGFRB gene, c.1681C>T (p.Arg561Cys) and c.1978C>A (p.Pro660Thr) have been reported. The c.1681C>T variant was reported in families from different ethnic and geographical populations (Cheng et al. 2013; Martignetti et al. 2013; Arts et al. 2016).

To date, only one heterozygous germline missense variant in NOTCH3, 4556T>C (p.Leu1519Pro), has been implicated in IM. This variant was identified via whole exome sequencing. Evidence for pathogenicity include co-segregation of the variant in a large family with a history of IM and no pathogenic variants in PDGFRB; absence from large population databases of genetic variations; and localization in the hetero-dimerization domain of the protein (Martignetti et al. 2013; Arts et al. 2016).

PDGFRB encodes the platelet-derived growth factor receptor beta, a tyrosine kinase receptor that is involved in several cellular processes including proliferation, differentiation, survival, and migration. It has also been suggested that the PDGFRB/ PDGFB pathway is involved in the calcification of vascular smooth muscle cells (Diliberto et al. 1991).

NOTCH3 encodes a transmembrane protein that is a member of the NOTCH receptor family. NOTCH signaling is involved in the regulation of various processes in both the embryo and the adult (Joutel 2000).

In vitro studies have previously revealed interactions between the Notch and PDGF signaling pathways (Jin et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the PDGFRB gene are the major cause of familial IM; they were found in about 90% of IM-affected families (Cheng et al. 2013; Martignetti et al. 2013). Pathogenic variants in the NOTCH3 gene appear to be a rare cause of IM. Such a variant was identified in one out of 9 IM-affected families (Martignetti et al. 2013).

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

Patients with clinical and radiological findings suggestive of infantile myofibromatosis are candidates.

Genes

Official Gene Symbol OMIM ID
NOTCH3 600276
PDGFRB 173410
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Arts F.A. et al. 2016. Oncogene. 35: 3239-48. PubMed ID: 26455322
  • Cheung Y.H. et al. 2013. American Journal of Human Genetics. 92: 996-1000. PubMed ID: 23731537
  • Chung E.B., Enzinger F.M. 1981. Cancer. 48: 1807-18. PubMed ID: 7284977
  • Diliberto P.A. et al. 1991. The Journal of Biological Chemistry. 266: 12612-7. PubMed ID: 1905727
  • Jin S. et al. 2008. Circulation Research. 102: 1483-91. PubMed ID: 18483410
  • Joutel A. et al. 2000. Annals of Neurology. 47: 388-91. PubMed ID: 10716263
  • Martignetti J.A. et al. 2013. American Journal of Human Genetics. 92: 1001-7. PubMed ID: 23731542
  • Narchi H. 2001. Clinical Genetics. 59: 134-5. PubMed ID: 11260217
  • Teng P. et al. 1963. . The Journal of Pediatrics. 62: 748-53. PubMed ID: 13980570
  • Wada H. et al. 1998. Journal of Pediatric Hematology/oncology. 20: 353-6. PubMed ID: 9703012
  • Wiswell T.E. et al. 1988. Journal of Pediatric Surgery. 23: 315-8. PubMed ID: 3385581

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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