• 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 (NGS) will analyze the exons or coding regions of the genes using Illumina NextSeq 500/550 technology and preparing samples using hybridization probes to enrich exonic regions.  This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.

Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.

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 Collection Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

  • Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

  • Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), 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)

  •  Prenatal
    • Direct Amniotic Fluid (10-20mL)
    • Direct CVS
    • Direct POC
    • Cultured Amniocytes (2 T-25 flasks
    • Cultured CVS (2 T-25 flasks)
    • Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)
    • Cord Blood (1-2mL)

    Notice Regarding Molecular Genetic Testing on Prenatal Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.

  • 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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