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Test ID: EDSGP Ehlers-Danlos Syndrome Panel (12 Genes), Next-Generation Sequencing and Deletion/Duplication Analysis, Varies


Advisory Information


Targeted testing for familial variants (also called site-specific or known mutation testing) is available for the genes on this panel. See:

-KVAR1 / Known Variant Analysis-1 Variant, Varies

-KVAR2 / Known Variant Analysis-2 Variants, Varies

-KVAR3 / Known Variant Analysis-3+ Variants, Varies

 

Call 800-533-1710 to confirm the appropriate test for targeted testing.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


1. Marfan and Related Disorders Patient Information (T636) is required, see Special Instructions. Testing may proceed without the patient information however it aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to complete the form and send it with the specimen.

2. Include physician name and phone number with specimen.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

 

Specimen Type: DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 250 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

Useful For

Confirmation of a clinical diagnosis of Ehlers-Danlos Syndrome (EDS)

 

Differentiating between the different subtypes of EDS for diagnosis and management purposes

 

Ascertaining carrier status of family members of individuals diagnosed with EDS for genetic counseling purposes

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Supplemental Sanger Sequencing or qPCR if needed

Reporting Name

Ehlers-Danlos Syndrome Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

Whole blood: 1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

The Ehlers Danlos syndromes (EDS) are a clinically and genetically diverse group of heritable connective tissue disorders. An EDS classification system proposed by the International EDS Consortium identifies 13 subtypes of EDS, with an overall estimated prevalence of EDS between 1:5,000 and 1:25,000. Over 90% of cases are either classic or hypermobile EDS (cEDS or hEDS), while less than 5% of cases are vascular EDS (vEDS). Other, rarer, subtypes of EDS also exist and are listed in the table below.

 

The clinical hallmarks of EDS are joint hypermobility, skin hyperextensibility, and tissue fragility. However, a variety of skin, ligament, joint, and cardiovascular features are seen across the spectrum of EDS. A clinical diagnosis of a specific subtype of EDS may be suspected based on a combination of major (a symptom present in the majority of affected individuals) and minor (a symptom of lesser diagnostic specificity that supports the diagnosis) clinical criteria. However, due to the clinical overlap between EDS subtypes and other heritable connective tissue disorders (eg, Marfan syndrome and Loeys-Dietz syndrome), a definitive diagnosis of all EDS subtypes (except EDS hypermobility type) relies on the identification of a causative variant in the appropriate gene.

 

Genetic variants in collagen-encoding or collagen-modifying genes have been identified as the cause of EDS in the majority of subtypes. These variants result in defects in collagen structure, processing, folding and cross-linking. One notable exception to this is hypermobile EDS (hEDS). Hypermobile EDS is inherited in an autosomal dominant inheritance pattern, similar to cEDS and vEDS, however, the molecular basis of this condition is unknown and a diagnosis is based on clinical criteria.

 

This panel also tests for variants in the ATP7A and FLNA genes, which result in X-linked conditions. Some patients with these conditions have clinical overlap with EDS.

Table1. Genes included in the EDS Gene Panel

GENE SYMBOL (ALIAS)

PROTEIN

INHERITANCE*

EDS CLASSIFICATION

ADAMTS2

Procollagen I N-proteinase (NPI)

AR

Dermatosparaxis EDS (dEDS) / human dermatosparaxis EDS VIIC

ATP7A

Copper-transporting ATPase 1

XL

Occipital horn syndrome

CHST14

Dermatan-4-sulfotransferase-1 (D4ST1)

AR

Musculocontractural EDS (mcEDS-CHST14)

COL1A1

Collagen alpha-1(I) chain

AD

AD

AD

Classical EDS (cEDS)

Vascular EDS (vEDS)

Arthrochalasia EDS (aEDS)

COL1A2

Collagen alpha-2(I) chain

AD

AR

Arthrochalasia EDS (aEDS)

Cardiac valvular EDS (cvEDS)

COL3A1

Collagen alpha-1(III) chain

AD

Vascular EDS (vEDS)

COL5A1

Collagen alpha-1(V) chain

AD

Classical EDS (cEDS)

COL5A2

Collagen alpha-2(V) chain

AD

Classical EDS (cEDS)

FKBP14

Peptidyl-prolyl cis-trans isomerase FKBP14 (FK506 binding protein 14)

AR

Kyphoscoliotic EDS (kEDS-FKBP14)

FLNA

Filamin A

XL

Filamin A related EDS with periventricular nodular heterotopia

PLOD1

Procollagen-lysine 5-dioxygenase

 

AR

Kyphoscoliotic EDS (kEDS – PLOD1)

SLC39A13

Zinc transporter ZIP13

AR

Spondylodysplastic EDS (spEDS-SLC39A13)

*Abbreviations: Autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), Ehlers-Danlos syndrome (EDS)

Reference Values

An interpretive report will be provided.

Interpretation

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Reference

1. Malfait F, Francomano C, Byers P, et al: The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi: 10.1002/ajmg.c.31552

2. Meester JAN, Verstraeten A, Schepers D, et al: Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg. 2017;6(6):582-594. doi: 10.21037/acs.2017.11.03

3. Brady AF, Demirdas S, Fournel-Gigleux S, et al: The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175(1):70-115. doi: 10.1002/ajmg.c.31550

4. Bowen JM, Sobey GJ, Burrows NP, et al: Ehlers-Danlos syndrome, classical type. Am J Med Genet C Semin Med Genet. 2017;175(1):27-39. doi: 10.1002/ajmg.c.31548

5. Bursztejn AC, Baumann M, Lipsker D: Ehlers-Danlos syndrome related to FKBP14 mutations: detailed cutaneous phenotype. Clin Exp Dermatol 2017;42(1):64-67. doi: 10.1111/ced.12983

Day(s) and Time(s) Performed

Wednesday; Varies

Analytic Time

2 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81479

81408 x 2 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
EDSGP Ehlers-Danlos Syndrome Gene Panel 93200-4

 

Result ID Test Result Name Result LOINC Value
601731 Gene(s) Evaluated 36908-2
601732 Result Summary 47997-2
601733 Result Details 82939-0
601734 Interpretation 69047-9
601735 Additional Information 48767-8
601736 Method 49549-9
601737 Disclaimer 62364-5
601738 Reviewed By 18771-6
Mayo Clinic Laboratories | Cardiology Catalog Additional Information:

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