• Test Code:
  • Department:
  • Test Synonyms:
    Marfan SyndromeLoeys-Dietz Syndrome (LDS)Ehlers-Danlos SyndromeFamilial Aneurysm and AortopathyShprintzen-Goldberg SyndromeACTA2ADAMTS2B3GALT6B4GALT7CBSCHST14COL1A1COL1A2COL3A1COL5A1COL5A2FBN1 FBN2FKBP14FLNAMED12MYH11MYLKNOTCH1PLOD1PRDM5SKISLC2A10SLC39A13SMAD3TGFB2TGFB3TGFBR1TGFBR2TNXBZNF469
  • CPT Code(s):

The inherited connective tissue disorders comprise a group of genetically heterogeneous diseases including: Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome. This group of disorders primarily affects the skeletal and cardiovascular systems.  Marfan syndrome is a clinically variable disorder involving the cardiovascular, ocular, and skeletal systems. Primary manifestations for Marfan syndrome include aortic dilation and/or dissection, myopia, retinal detachment, glaucoma, bone overgrowth, and joint laxity. Loeys-Dietz syndrome is characterized by skeletal abnormalities with aneurysms and/or dissections of the cerebral, thoracic, and abdominal arteries. Ehlers-Danlos syndrome is a disorder defined by smooth, hyperelastic skin, abnormal wound healing and bruising, joint hypermobility, and risk for arterial rupture. This next-generation sequencing test is designed to detect mutations in the coding region of 31 genes associated with Connective Tissue Disorders.

Reasons for Referral:

  • Aortic or arterial aneurysms and/or dissections.
  • Clinical presentation consistent with Marfan syndrome, Loeys-Dietz Syndrome, or Ehlers-Danlos Syndrome.
  • Positive family history for connective tissue disorders (targeted testing is available if familial mutation is known).
  • Carrier testing.


Next generation sequencing will analyze the exons or coding regions of 31 Connective Tissue Disorder genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions.   Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.

Connective Tissue Panel (31 genes): ACTA2, ADAMTS2, B3GALT6, B4GALT7, CBS, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, FBN1, FBN2, FKBP14, FLNA, MED12, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, SKI, SLC2A10, SLC39A13, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, ZNF469

Specimen Requirements:

  • Blood:  EDTA or ACD (Solution A or B):
  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL
  • Saliva: 2 ORAgene Saliva Kits (OGR-500)
  • Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks
  • DNA: 3-4µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):


Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.


  1. GeneReviews:
    1. Dietz, 2014, http://www.ncbi.nlm.nih.gov/books/NBK1335/
    2. Loeys et al., 2013, http://www.ncbi.nlm.nih.gov/books/NBK1133/
    3. Malfait et al., 2011, http://www.ncbi.nlm.nih.gov/books/NBK1244/ 
  2. Genetics Home Reference:
    1. http://ghr.nlm.nih.gov/condition/marfan-syndrome
    2. http://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome
    3. http://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome

Additional Info:

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