Marfan Syndrome/LDS/Related Disorders

Marfan syndrome (MFS) is a connective tissue disorder that can affect multiple organ systems including the skeletal, ocular, and cardiovascular systems and is caused by mutations in the FBN1 gene. A diagnosis is based on the presence of major and minor clinical criteria, as established by the Ghent nosology (de Paepe 1996, Loeys 2010). Skeletal features can include chest malformations (pectus carinatum/excavatum), tall stature, increased joint mobility, and scoliosis. Eye findings most commonly include lens dislocation (ectopia lentis) and myopia. The cardiovascular features are typically mitral valve prolapse and/or aortic root dilatation, which can progress to aortic dissection. Patient management and treatment is mainly focused on slowing the progression of aortic root dilation, the most common cause of morbidity and early mortality. Therefore, genetic testing is important for identifying presymptomatic family members who carry a FBN1 mutation, and at risk for developing features of Marfan syndrome, who will benefit from appropriate monitoring for aortic root dilatation.
Mutations in the FBN1 gene have also been observed in families with isolated ectopia lentis and MASS syndrome (myopia, mitral valve prolapse, borderline/non-progressive aortic root dilation, skeletal and skin findings). MASS is a connective tissue disorder related to Marfan syndrome but with milder cardiovascular findings.

Loeys-Dietz syndrome (LDS) is a systemic connective tissue disorder caused by mutations in the TGFBR1 or TGFBR2 genes (also available as part of the 16 gene Marfan syndrome/TAAD sequencing panel). The skeletal features of Loeys-Dietz syndrome, such as joint laxity, arachnodactyly, pectus deformity, and scoliosis, can overlap with the Marfan phenotype, however most individuals with LDS have features in other organ systems not typical of Marfan syndrome (Loeys 2005). Patients with Loeys-Dietz syndrome can exhibit various craniofacial, neurodevelopmental, skeletal and skin abnormalties, however features specific to LDS include hypertelorism, cleft palate or bifid uvula, and arterial or aortic aneurysms and aterial tortuosity (Van Hemelrijk 2010). The primary risk for early mortality is due to aterial tortuosity and/or aortic root dilatation, which results in an increased risk of aterial or aortic aneurysm (Van Hemelrijk 2010). Since patients with LDS can develop potentially lethal arterial aneurysms that would not be detected by echocardiogram, differentiating between Loeys-Dietz and Marfan syndromes is necessary to determine the appropriate clinical management. Similar to Marfan syndrome, genetic testing is important for identifying presymptomatic family members at risk for developing Loeys-Dietz syndrome.

Mutations in the TGFBR1 gene have also been observed in families with multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease. MSSE is a skin cancer condition that presents with multiple, locally invasive skin tumors that normally regress, leaving scars. Loss-of-function mutations in the TGFBR1 gene have been reported in individuals with MSSE, while gain-of-function mutations are presumed to result in the Loeys-Dietz syndrome phenotype (Goudie 2011)

Tests Available

Forms and Documents

Test Details

ACTA2, BGN, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, FLNA, LOX, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PRKG1, SKI, SLC2A10, SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2
  • Confirmation of clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with TAAD
  • Differentiation between familial TAAD, Marfan syndrome, Loeys-Dietz syndrome and phenotypically related disorders.
  • Deletion/Duplication Analysis
  • Next-Gen Sequencing

Ordering

883
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81410x1, 81411x1
Yes
Yes
  • 441.9 Aortic aneurysm of unspecified site without mention of rupture Aneurysm Dilatation of aorta, Hyaline necrosis of aorta
  • 441.5 Aortic aneurysm of unspecified site, ruptured Rupture of aorta NOS
  • 759.82 Marfan syndrome
  • 759.7 Multiple congenital anomalies, so described Congenital: anomaly, multiple NOS deformity, multiple NOS
  • 512.8 Other spontaneous pneumothorax Pneumothorax
  • 754.81 Pectus excavatum Congenital funnel chest
  • 737.43 Scoliosis
  • 701.3 Striae atrophicae, Atrophic spots of skin, Atrophoderma maculatum, Atrophy blanche (of Milian), Degenerative colloid atrophy, Senile degenerative atrophy, Striae distensae
  • 379.32 Subluxation of lens
  • 441.00 Unspecified site
* For price inquiries please email zebras@genedx.com

Forms and Documents

Test Details

FBN1
  • Confirmation of clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with TAAD
  • Differentiation between familial TAAD, Marfan syndrome, Loeys-Dietz syndrome and phenotypically related disorders
  • Deletion/Duplication Analysis
  • Next-Gen Sequencing

Ordering

918
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81408x1, 81479x1
Yes
Yes
  • 441.9 Aortic aneurysm of unspecified site without mention of rupture Aneurysm Dilatation of aorta, Hyaline necrosis of aorta
  • 441.5 Aortic aneurysm of unspecified site, ruptured Rupture of aorta NOS
  • 759.82 Marfan syndrome
  • 759.7 Multiple congenital anomalies, so described Congenital: anomaly, multiple NOS deformity, multiple NOS
  • 512.8 Other spontaneous pneumothorax Pneumothorax
  • 754.81 Pectus excavatum Congenital funnel chest
  • 737.43 Scoliosis
  • 701.3 Striae atrophicae, Atrophic spots of skin, Atrophoderma maculatum, Atrophy blanche (of Milian), Degenerative colloid atrophy, Senile degenerative atrophy, Striae distensae
  • 379.32 Subluxation of lens
  • 441.00 Unspecified site
* For price inquiries please email zebras@genedx.com

Forms and Documents

Test Details

ACTA2, ADAMTS2, ALDH18A1, ATP6V0A2, ATP6V1E1, ATP7A, B3GALT6, B3GAT3, B4GALT7, BGN, CBS, CHST14, COL11A1, COL11A2, COL12A1, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL9A1, COL9A2, COL9A3, DSE, EFEMP2, ELN, FBLN5, FBN1, FBN2, FKBP14, FLNA, LOX, LTBP4, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, PYCR1, RIN2, SKI, SLC2A10, SLC39A13, SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, ZNF469
  • Molecular confirmation of a clinical diagnosis in symptomatic individuals
  • Risk assessment of asymptomatic family members of a proband diagnosed with a heritable connective tissue disorder
  • Genetic counseling and recurrence risk determination
  • Deletion/Duplication Analysis
  • Next-Gen Sequencing

Ordering

J555
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81410x1, 81411x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

Test Details

ACTA2, BGN, CBS, COL3A1, COL5A1, COL5A2, FBN2, FLNA, LOX, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PRKG1, SKI, SLC2A10, SMAD2, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2
  • Confirmation of clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with TAAD
  • Differentiation between familial TAAD, Marfan syndrome, Loeys-Dietz syndrome and phenotypically related disorders.
  • Deletion/Duplication Analysis
  • Next-Gen Sequencing

Ordering

919
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81405x2, 81406x2, 81408x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of clinical diagnosis in symptomatic patients
  • Genetic counseling and risk assessment of asymptomatic family members of a proband with a hereditary cardiovascular condition

Customizable Cardiology Panel

  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

J779
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

Varies by gene
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of clinical diagnosis in symptomatic patients
  • Risk assessment of asymptomatic family members of a proband with TAAD
  • Differentiation between familial TAAD, Marfan syndrome, Loeys-Dietz syndrome and phenotypically related disorders.

Customizable Cardiology Panel

  • Deletion/Duplication Analysis
  • Next-Gen Sequencing

Ordering

883C
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81410x1, 81411x1
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Molecular confirmation of a clinical diagnosis in symptomatic individuals
  • Risk assessment of asymptomatic family members of a proband diagnosed with a heritable connective tissue disorder
  • Genetic counseling and recurrence risk determination

Customizable Cardiology Panel

  • ExonArray CGH
  • Next-Gen Sequencing

Ordering

J555C
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81410x1, 81411x1
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

Test Details

ADAMTS2, ALDH18A1, ATP6V0A2, ATP6V1E1, ATP7A, B3GALT6, B3GAT3, B4GALT7, CHST14, COL11A1, COL11A2, COL12A1, COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, DSE, EFEMP2, ELN, FBLN5, FBN1, FKBP14, LTBP4, PLOD1, PRDM5, PYCR1, RIN2, SLC39A13, TNXB, ZNF469
  • Molecular confirmation of a clinical diagnosis in symptomatic individuals
  • Risk assessment of asymptomatic family members of a proband diagnosed with a heritable connective
  • tissue disorder
  • Genetic counseling and recurrence risk determination
  • Next-Gen Sequencing
  • ExonArray CGH

Ordering

883RE
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81408x2; 81479x1
Yes
Yes
* For price inquiries please email zebras@genedx.com