Marfan Syndrome and Related Aortopathies Panel (PG-Select)

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
1212 ACTA2 81405,81479 Order Options and Pricing
CBS 81406,81479
COL3A1 81479,81479
COL5A1 81479,81479
COL5A2 81479,81479
EFEMP2 81479,81479
ELN 81479,81479
FBLN5 81479,81479
FBN1 81408,81479
FBN2 81479,81479
FLNA 81479,81479
FOXE3 81479,81479
LOX 81479,81479
MAT2A 81479,81479
MED12 81479,81479
MFAP5 81479,81479
MYH11 81408,81479
MYLK 81479,81479
NOTCH1 81407,81479
PLOD1 81479,81479
PRKG1 81479,81479
SKI 81479,81479
SLC2A10 81479,81479
SMAD3 81479,81479
SMAD4 81406,81405
SMS 81479,81479
TGFB2 81479,81479
TGFB3 81479,81479
TGFBR1 81405,81479
TGFBR2 81405,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
1212Genes x (30)81410 81405, 81406, 81407, 81408, 81479 $640 Order Options and Pricing

Pricing Comments

CPT codes 81410 and 81411 can be used if analysis includes FBN1, TGFBR1, TGFBR2, COL3A1, MYH11, ACTA2, SLC2A10, SMAD3, and MYLK.

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.

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.

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

This panel tests for syndromic and non-syndromic causes of thoracic aortic aneurysm and dissection (TAAD). TAAD is a life-threatening disease affecting the aorta and is the 15th leading cause of death in the United States (Hoyert et al. 2001. PubMed ID: 11591077). Aortic dissections most commonly originate in the ascending aorta above the aortic valve (Stanford type A), but also can occur in the descending aorta (Stanford type B). Aneurysms in the cerebral and peripheral artery and abdominal aorta have also been observed (Milewicz and Regalado. 2012. PubMed ID: 20301299). An intense sharp pain in the chest is the most common symptom of aortic dissection. Familial TAAD is diagnosed based on the presence of dilatation and/or dissection of the thoracic aorta using imaging studies (MRI, echocardiography, CT), the absence of syndromic conditions that have clinical features that overlap with familial TAAD, and a positive family history. Syndromic forms of TAAD include Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, Shprintzen-Golberg syndrome, congenital contractural arachnodactyly, aneurysms-osteoarthritis syndrome, multisystemic smooth muscle dysfunction syndrome, Ehlers-Danlos syndrome (vascular type, classic type, and kyphoscoliosis form), and periventricular nodular heterotopia.

Lujan syndrome, homocystinuria, and Snyder-Robinson syndrome have phenotypic overlap with Marfan syndrome. Patients with Lujan syndrome have cognitive impairment and marfanoid habitus, and craniofacial dysmorphisms (Lujan et al. 1984. PubMed ID: 6711603; Schwartz et al. 2007. PubMed ID: 17369503). Classic homocystinuria symptoms include developmental delay or intellectual disability, ectopia lentis and/or severe myopia, skeletal abnormalities, osteoporosis, and vascular disease, including potentially fatal thromboembolisms (Kraus et al. 1999. PubMed ID: 10338090; Picker and Levy. 2014. PubMed ID:20301697; Mudd et al. 2014). Snyder-Robinson syndrome is characterized by mild to moderate X-linked intellectual disability, seizures, speech and gait abnormalities, marfanoid habitus, hypotonia and movement disorders, skeletal changes caused by osteoporosis, and facial dysmorphism (Cason et al. 2003. PubMed ID: 14508504; Becerra-Solano et al. 2009. PubMed ID: 19206178; Albert et al. 2015. PubMed ID: 25888122).

Supravalvular aortic stenosis is a congenital narrowing of the ascending aorta. The narrowing of the aorta can lead to shortness of breath, chest pain and heart failure. Supravalvular aortic stenosis can occur as an isolated condition or as one feature of Williams-Beuren syndrome (Metcalfe et al. 2000. PubMed ID: 11175284).

Cutis laxa is characterized by loose, sagging skin. Occasionally, aortic aneurysms and obstructive pulmonary disease are present (Callewaert et al. 2011. PubMed ID: 21309044). Aortic imaging is recommended in first degree relatives of individuals with TAAD. Age of onset of dilatation is variable within families.

Genetics

Marfan syndrome, Loeys-Dietz syndrome, congenital contractural arachnodactyly, Shprintzen-Golberg syndrome, aneurysms-osteoarthritis syndrome, multisystemic smooth muscle dysfunction syndrome, supravalvar aortic stenosis, cutis laxa, Ehlers-Danlos vascular and classic type, and familial TAAD are inherited in an autosomal dominant manner due to pathogenic variants in the FBN1, TGFBR1, TGFBR2, TGFB2, TGB3, FBN2, SKI, ELN, FBLN5, COL5A1, COL5A2, COL3A1, MYLK, MYH11, ACTA2, FOXE3, LOX, MAT2A, MFAP5, NOTCH1, PRKG1, SMAD3, and SMAD4 genes. Arterial tortuosity syndrome, cutis laxa, homocystinuria, and Ehlers-Danlos syndrome, type VI are inherited in an autosomal recessive manner due to pathogenic variants in SLC2A10, EFEMP2, FBLN5, CBS, and PLOD1, respectively. FG syndrome, Lujan syndrome, and Snyder Robinson syndrome are inherited in an X-linked manner due to FLNA, MED12, and SMS genes.

See individual test descriptions for information on molecular biology of gene products and mutation spectra.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect a disease-causing variant in approximately 30% of individuals with familial thoracic aortic aneurysm and dissection (TAAD) (Milewicz and Regalado 2012. PubMed ID: 20301299). FBN1 pathogenic variants have been identified in up to 90% of patients with a clinical diagnosis of Marfan syndrome based on the Ghent nosology (Dietz 2011. PubMed ID: 20301510; Mátyás et al. 2007. PubMed ID: 17492313). FBN2 pathogenic variants have been identified in up to 75% of individuals diagnosed with congenital contractural arachnodactyly (CCA) (Nishimura et al. 2007. PubMed ID: 17345643). More than 95% of patients with clinical findings consistent with Loeys-Dietz have a pathogenic variant in TGFBR1 or TGFBR2 (Loeys and Dietz. 2013. PubMed ID: 20301312). COL3A1 pathogenic variants have been identified in approximately 95% of individuals with Ehlers-Danlos syndrome (EDS) IV (Pepin and Byers. 2011. PubMed ID: 20301667). COL5A1 and COL5A2 pathogenic variants have been identified in at least 50% of affected individuals with classic EDS (Malfait et al. 2011). Twenty-eight out of 29 individuals with Shprintzen-Goldberg syndrome were found to have a pathogenic variant in SKI (Carmignac et al. 2012. PubMed ID: 23103230; Doyle et al. 2012. PubMed ID: 23023332). FLNA pathogenic variants were identified in 26 out of 41 patients with FLNA-related disorders (OPD1, OPD2, FMD, MNS) (Robertson et al. 2003. PubMed ID: 12612583). 95-98% of patients with homocystinuria are found to harbor two pathogenic variants (Gaustadnes et al. 2002. PubMed ID: 12124992; Kruger et al. 2003. PubMed ID: 14635102; Cozar et al. 2011. PubMed ID: 21520339; Karaca et al. 2014. PubMed ID: 24211323). Nine out of 12 individuals with EDS type VIA were found to have a pathogenic variant in PLOD1 (Rohrbach et al. 2011. PubMed ID: 21699693). This test is predicted to detect pathogenic variants in 22%-35% of Supravalvar aortic stenosis patients that do not have gross deletions in the ELN gene (Metcalfe et al. 2000. PubMed ID: 11175284; Micale et al. 2010. PubMed ID: 19844261). Deletions of 7q11.23 which encompasses the ELN gene are commonly found in individuals with Williams syndrome. This NGS test will only detect copy number changes in the ELN gene, therefore we will not be able to determine how many additional genes are deleted in patients with Williams syndrome.

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with non-syndromic and syndromic forms of thoracic aortic aneurysm and dissection. Syndromic forms include Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, Shprintzen-Golberg syndrome, aneurysms-osteoarthritis syndrome, multisystemic smooth muscle dysfunction syndrome, congenital contractural arachnodactyly, cutis laxa, Ehlers-Danlos vascular type, Ehlers-Danlos classic type, and Ehlers-Danlos kyphoscoliosis form. Lujan syndrome, homocystinuria, and Snyder-Robinson syndrome are included in this panel as a differential for Marfan syndrome.

Related Test

Name
PGxome®

Citations

  • Albert et al. 2015. PubMed ID: 25888122
  • Becerra-Solano et al. 2009. PubMed ID: 19206178
  • Callewaert et al. 2011. PubMed ID: 21309044
  • Cason et al. 2003. PubMed ID: 14508504
  • Cozar et al. 2011. PubMed ID: 21520339
  • Dietz. 2017. PubMed ID: 20301510
  • Doyle et al. 2012. PubMed ID: 23023332
  • Gaustadnes et al. 2002. PubMed ID: 12124992
  • Hoyert et al. 2001. PubMed ID: 11591077
  • Karaca et al. 2014. PubMed ID: 24211323
  • Kraus et al. 1999. PubMed ID: 10338090
  • Kruger et al. 2003. PubMed ID: 14635102
  • Loeys and Dietz. 2013. PubMed ID: 20301312
  • Lujan et al. 1984. PubMed ID: 6711603
  • Malfait et al. 2018. PubMed ID: 20301422
  • Mátyás et al. 2007. PubMed ID: 17492313
  • Metcalfe et al. 2000. PubMed ID: 11175284
  • Micale et al. 2010. PubMed ID: 19844261
  • Milewicz and Regalado. 2012. PubMed ID: 20301299
  • Mudd et al. 2014. Disorders of Transsulfuration. In: Valle D, Beaudet AL, Vogelstein B, et al., editors.New York, NY: McGraw-Hill. OMMBID. 
  • Nishimura et al. 2007. PubMed ID: 17345643
  • Pepin and Byers. 2011. PubMed ID: 20301667
  • Robertson et al. 2003. PubMed ID: 12612583
  • Rohrbach et al. 2011. PubMed ID: 21699693
  • Sacharow et al. 2017. PubMed ID: 20301697
  • Schwartz et al. 2007. PubMed ID: 17369503
  • Zhu et al. 2006. PubMed ID: 16444274

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

loading Loading... ×

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.

Total Price: $
×
Copy Text to Clipboard
×