Marfan Syndrome and Related Aortopathies Panel (Exome)

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10363 ACTA2 81405,81479 Order Options and Pricing
AEBP1 81479,81479
BGN 81479,81479
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
LTBP3 81479,81479
MAT2A 81479,81479
MED12 81479,81479
MFAP5 81479,81479
MYH11 81408,81479
MYLK 81479,81479
NKAP 81479,81479
NOTCH1 81407,81479
PLOD1 81479,81479
PRKG1 81479,81479
SKI 81479,81479
SLC2A10 81479,81479
SMAD2 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
10363Genes x (35)81410 81405, 81406, 81407, 81408, 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

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 can also 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. 2017. 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, Snyder-Robinson syndrome, Meester-Loeys syndrome, and X-linked intellectual disability Hackman-Di Donato type have phenotypic overlap with Marfan syndrome. Patients with Lujan syndrome have cognitive impairment, marfanoid habitus, and craniofacial dysmorphisms (Schwartz et al. 2007. PubMed ID: 17369503). Classic homocystinuria symptoms include developmental delay or intellectual disability, ectopia lentis with or without severe myopia, skeletal abnormalities, osteoporosis, and vascular disease, including potentially fatal thromboembolisms (Sacharow et al. 2017. 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, movement disorders, skeletal changes caused by osteoporosis, and facial dysmorphism (Schwartz et al. 1993. PubMed ID: 23805436). Meester-Loeys syndrome is characterized by X-linked early-onset aortic aneurysm and dissection, joint hypermobility, and other skeletal abnormalities (Meester et al. 2017. PubMed ID: 27632686). X-linked intellectual disability Hackman-Di Donato type is characterized by global developmental delay and marfanoid habitus (Fiordaliso et al. 2019. PubMed ID: 31587868).

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 is highly variable and may occur as early as the perinatal stage to 60-70 years of age (Veiga-Fernández et al. 2020. PubMed ID: 30652519; Hagan et al. 2000. PubMed ID: 10685714).

Advantages of genetic testing for Marfan syndrome and related aortopathies include confirmation of diagnosis, identification of other health risks associated with TAAD, targeted testing of other family members, and assistance with reproductive planning. An early diagnosis of TAAD followed by prophylactic surgical repair and early medical treatment has been demonstrated to reduce the mortality rate (Mody et al. 2014. PubMed ID: 25336626).

Genetics

Marfan syndrome and related aortopathies may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner, or may arise de novo. Marfan syndrome, Loeys-Dietz syndrome, congenital contractural arachnodactyly, Shprintzen-Golberg syndrome, the vascular and classic types of Ehlers-Danlos syndrome, aneurysms-osteoarthritis syndrome, multisystemic smooth muscle dysfunction syndrome, supravalvar aortic stenosis, cutis laxa, and familial TAAD are inherited in an autosomal dominant manner due to pathogenic variants in the ACTA2, AEBP1, COL3A1, COL5A1, COL5A2, ELN, FBLN5, FBN1, FBN2, FOXE3, LOX, MAT2A, MFAP5, MYH11, MYLK, NOTCH1, PRKG1, SKI, SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, and TGFBR2 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 CBS, EFEMP2, FBLN5, LTBP3, PLOD1, and SLC2A10. X-linked inheritance is observed in FG syndrome, Lujan syndrome, Snyder Robinson syndrome, X-linked intellectual disability Hackman-Di Donato type, and Meester-Loeys syndrome, caused by pathogenic variants in the BGN, FLNA, MED12, NKAP, and SMS genes. Pathogenic missense, nonsense, frameshift, and splicing variants as well as CNV events have been reported in genes associated with Marfan syndrome and related aortopathies (Dietz et al. 2017. PubMed ID: 20301510; Milewicz et al. 2017. PubMed ID: 20301299). 

Pathogenic variants that are associated with TAAD are largely found in genes involved in TGF-β pathway, extracellular matrix and collagen homeostasis, and smooth muscle cell contractile apparatus (Chou and Lindsay. 2020. PubMed ID: 32034893).

See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect a disease-causing variant in approximately 30% of individuals with familial TAAD (Milewicz and Regalado 2017. 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. 2017. 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 (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. 2018. PubMed ID: 20301422). 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).

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).

95-98% of patients with homocystinuria are found to harbor two pathogenic variants in CBS (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).

This test is predicted to detect pathogenic variants in 22%-35% of supravalvar aortic stenosis patients who do not have gross deletions in the ELN gene (Metcalfe et al. 2000. PubMed ID: 11175284; Micale et al. 2010. PubMed ID: 19844261). 

Testing Strategy

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

This panel typically provides 99.7% 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

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, Snyder-Robinson syndrome, and Meester-Loeys syndrome are included in this panel as a differential for Marfan syndrome.

Diseases

Name Inheritance OMIM ID
Aortic Aneurysm, Familial Thoracic 10 AD 617168
Aortic Aneurysm, Familial Thoracic 11, susceptibility to AD 617349
Aortic Aneurysm, Familial Thoracic 4 AD 132900
Aortic Aneurysm, Familial Thoracic 6 AD 611788
Aortic Aneurysm, Familial Thoracic 7 AD 613780
Aortic Aneurysm, Familial Thoracic 8 AD 615436
Aortic Aneurysm, Familial Thoracic 9 AD 616166
Aortic Valve Disorder AD 109730
Arterial Tortuosity Syndrome AR 208050
Congenital Contractural Arachnodactyly AD 121050
Cutis Laxa, Autosomal Dominant AD 123700
Cutis Laxa, Autosomal Dominant 2 AD 614434
Cutis Laxa, Autosomal Recessive, Type IA AR 219100
Cutis Laxa, Autosomal Recessive, Type IB AR 614437
Dental Anomalies and Short Stature AR 601216
Ehlers-Danlos Syndrome, Classic Like, 2 AR 618000
Ehlers-Danlos Syndrome, Hydroxylysine-Deficient AR 225400
Ehlers-Danlos Syndrome, Type 1 AD 130000
Ehlers-Danlos Syndrome, Type 2 AD 130010
Ehlers-Danlos Syndrome, Type 3 AD 130020
Ehlers-Danlos Syndrome, Type 4 AD 130050
FG Syndrome 2 XL 300321
Geleophysic dysplasia 3 AD 617809
Homocystinuria Due To Cbs Deficiency AR 236200
Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type XL 301039
Loeys-Dietz Syndrome 1 AD 609192
Loeys-Dietz Syndrome 2 AD 610168
Loeys-Dietz Syndrome 3 AD 613795
Loeys-Dietz Syndrome 4 AD 614816
Loeys-Dietz Syndrome 5 AD 615582
Lujan-Fryns Syndrome XL 309520
Marfan Syndrome AD 154700
Meester-Loeys syndrome XL 300989
Moyamoya Disease 5 AD 614042
Multisystemic Smooth Muscle Dysfunction Syndrome AD 613834
Shprintzen-Goldberg Syndrome AD 182212
Snyder Robinson Syndrome XL 309583
Spondyloepimetaphyseal dysplasia, X-linked XL 300106

Related Test

Name
PGxome®

Citations

  • Callewaert et al. 2011. PubMed ID: 21309044
  • Carmignac et al. 2012. PubMed ID: 23103230
  • Chou and Lindsay. 2020. PubMed ID: 32034893
  • Cozar et al. 2011. PubMed ID: 21520339
  • Dietz. 2017. PubMed ID: 20301510
  • Doyle et al. 2012. PubMed ID: 23023332
  • Fiordaliso et al. 2019. PubMed ID: 31587868
  • Gaustadnes et al. 2002. PubMed ID: 12124992
  • Hagan et al. 2000. PubMed ID: 10685714
  • Hoyert et al. 2001. PubMed ID: 11591077
  • Karaca et al. 2014. PubMed ID: 24211323
  • Kruger et al. 2003. PubMed ID: 14635102
  • Loeys and Dietz. 2013. PubMed ID: 20301312
  • Malfait et al. 2018. PubMed ID: 20301422
  • Mátyás et al. 2007. PubMed ID: 17492313
  • Meester et al. 2017. PubMed ID: 27632686
  • Metcalfe et al. 2000. PubMed ID: 11175284
  • Micale et al. 2010. PubMed ID: 19844261
  • Milewicz and Regalado. 2012. PubMed ID: 20301299
  • Milewicz et al. 2017. PubMed ID: 20301299
  • Mody et al. 2014. PubMed ID: 25336626
  • 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
  • Rohrbach et al. 2011. PubMed ID: 21699693
  • Sacharow et al. 2017. PubMed ID: 20301697
  • Schwartz et al. 1993. PubMed ID: 23805436
  • Schwartz et al. 2007. PubMed ID: 17369503
  • Veiga-Fernández et al. 2020. PubMed ID: 30652519

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

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