Ehlers-Danlos Syndrome (EDS) Diagnostic Panel

A targeted 19-gene diagnostic test for Ehlers-Danlos syndrome and its heritable subtypes, powered by the Helix Exome+® platform.

Turnaround

6-21 days

Requery (SOQO)

≤ 5 days

Genes Tested

Test Description

The Helix EDS Diagnostic Panel (EDSP1) is a 19-gene diagnostic test that evaluates coding regions associated with Ehlers-Danlos syndrome (EDS). Genes on this panel are associated with multiple EDS subtypes as classified by the 2017 International Classification of the Ehlers-Danlos Syndromes, including classical, vascular, kyphoscoliotic, dermatosparaxis, spondylodysplastic, musculocontractural, myopathic, classical-like, periodontal, and brittle cornea syndrome.

Full Description (PDF)

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Indications for Testing

A relevant personal and/or family history suggestive of Ehlers-Danlos syndrome and its various subtypes should be considered. Clinical triggers that should prompt consideration include joint hypermobility with progressive pain, instability, or functional limitation; recurrent joint dislocations or subluxations without clear traumatic cause; skin hyperextensibility, fragility, or easy bruising; unexplained aortic root dilation, arterial aneurysm, or spontaneous arterial dissection; progressive scoliosis or kyphosis with connective tissue features; muscle weakness combined with joint laxity; or a family history of EDS or an EDS subtype.

Methodology

This test utilizes next-generation sequencing to detect single nucleotide variants, insertions and deletions up to 20 bp, and copy number variants in genes associated with Ehlers-Danlos syndrome and related heritable connective tissue disorders. Data is aligned to GRCh38 and analyzed using MANE and MANE Plus Clinical transcripts. Variant interpretation is performed in accordance with ACMG/AMP guidelines and ClinGen Variant Curation Expert Panel modifications, when available. Helix is not affiliated with, endorsed by, or sponsored by the American College of Medical Genetics and Genomics (ACMG) or the Association for Molecular Pathology (AMP). The trademarks referring to these entities are owned by their respective organizations. All references are for identification purposes only and do not imply any association, sponsorship, or endorsement.

Technical Specifications

Analytical Sensitivity (SNV)

> 99.9%

Analytical Sensitivity (Indel)

> 99%

Analytical Specificity

> 99%

CNV Sensitivity (multi-exon)

> 99%

CNV Sensitivity (single-exon)

> 90%

Genomic Build

GRCh38

Limitations

This test may not detect variants in challenging regions (such as short tandem repeats, homopolymer runs, and segment duplications), sub-exonic CNVs, chromosomal aneuploidy, or variants in the presence of mosaicism. Phasing will be attempted and reported, when possible. Structural rearrangements such as inversions, translocations, and gene conversions are not tested in this assay unless explicitly indicated. Additionally, deep intronic, promoter, and enhancer regions may not be covered. A negative result does not guarantee that the tested individual does not carry a rare, undetectable variant in genes analyzed. Any potential incidental findings outside of these genes and conditions will not be identified, nor reported.

Genes Tested

19 genes included in this panel

ADAMTS2AEBP1B3GALT6B4GALT7C1RC1SCHST14COL1A1COL1A2COL3A1COL5A1COL5A2COL12A1DSEFKBP14PLOD1PRDM5SLC39A13ZNF469

Ordering Information

Turnaround Time

Typically 6 to 21 days from sample receipt (standard). Typically ≤ 5 days (requery / Sequence Once Query Often® (SOQO)®).

Preferred Specimen

Blood, saliva, or buccal swab

Shipping Instructions

Specimens to arrive at Helix within 96 hours of collection at ambient temperature.

Clinical Description

Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical spectrum ranges from mild joint hypermobility to severe, life-threatening vascular complications. The genes on this panel are associated with multiple EDS subtypes as classified by the 2017 International Classification of the Ehlers-Danlos Syndromes (1), as well as brittle cornea syndrome. These subtypes vary in severity and clinical features but share overlapping characteristics related to defects in collagen structure, processing, or modification. Inheritance may be autosomal dominant and/or autosomal recessive. The panel was specifically curated for genes with established association with EDS and related conditions. Identification of a pathogenic variant may establish a molecular diagnosis, inform prognosis and management, and facilitate genetic counseling for the patient and their family members. EDS subtypes covered by this panel include: Classical EDS (COL5A1, COL5A2, and rare COL1A1 variants) Vascular EDS (COL3A1) Kyphoscoliotic EDS (PLOD1, FKBP14) Dermatosparaxis EDS (ADAMTS2) Arthrochalasia EDS (COL1A1, COL1A2) Cardiac-valvular EDS (COL1A2) Classical-like EDS, type 2 (AEBP1) Musculocontractural EDS (CHST14, DSE) Myopathic EDS (COL12A1) Periodontal EDS (C1R, C1S) Spondylodysplastic EDS (B4GALT7, B3GALT6, SLC39A13) Brittle cornea syndrome (ZNF469, PRDM5) Note: This panel does not include TNXB, the gene classically associated with classical-like EDS type 1 in the 2017 International Classification of the Ehlers-Danlos Syndromes (1). Hypermobile EDS (hEDS) currently has no established monogenic etiology and is not covered by this panel. References Malfait F, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552. PMID: 28306229.

Frequently asked questions

What EDS subtypes does this panel cover?

The panel covers a broad range of EDS subtypes as classified by the 2017 International Classification of the Ehlers-Danlos Syndromes (1), including: Classical EDS (COL5A1, COL5A2, COL1A1), Vascular EDS (COL3A1), Kyphoscoliotic EDS (PLOD1, FKBP14), Dermatosparaxis EDS (ADAMTS2), Arthrochalasia EDS (COL1A1, COL1A2), Cardiac-valvular EDS (COL1A2), AEBP1-related EDS (AEBP1) - joint hypermobility, skin fragility, easy bruising, Musculocontractural EDS (CHST14, DSE), Myopathic EDS (COL12A1), Periodontal EDS (C1R, C1S), Spondylodysplastic EDS (B4GALT7, B3GALT6, SLC39A13), and Brittle cornea syndrome (ZNF469, PRDM5). Note: This panel does not include TNXB, the gene associated with classical-like EDS type 1 in the 2017 International Classification of the Ehlers-Danlos Syndromes (1). The genes COL1A1 and COL1A2 are also associated with osteogenesis imperfecta.

Does this panel cover hypermobile EDS (hEDS)?

No. Hypermobile EDS (hEDS) is the most common EDS subtype, but its genetic cause has not been definitively identified. As a result, there is no gene on this panel designated specifically for hEDS, and a negative result on this panel does not rule out hEDS. However, this panel does include genes for all other EDS subtypes, including subtypes that can present similarly to hEDS in a clinical setting. Identifying variants in these genes may be clinically meaningful, as those subtypes carry distinct inheritance patterns, management implications, and recurrence risks. For a patient presenting with suspected hEDS, this panel can help rule in or rule out a genetically identifiable EDS subtype.

What are the indications for ordering this panel?

The EDS panel is indicated for patients with a relevant personal and/or family history suggestive of Ehlers-Danlos syndrome or one of its subtypes. Clinical triggers include joint hypermobility, skin hyperextensibility, tissue fragility, unexplained aortic or arterial aneurysm, progressive scoliosis, skin fragility with easy bruising, or other connective tissue findings consistent with EDS. Providers should consider this panel when they suspect an EDS subtype with a known genetic basis.

What variant types does this test detect?

This test detects single nucleotide variants (SNVs), insertions and deletions (indels) up to 20 bp, and copy number variants (CNVs). Based on validation studies, the assay delivers >99% sensitivity and specificity for SNVs and indels up to 20 bp. Larger indels and complex variants are also reported, but sensitivity may be reduced.

Will variants of uncertain significance (VUS) be reported?

Yes. Because this is a diagnostic test (typically ordered for patients with signs, symptoms, or family history suggestive of EDS), VUS findings are included in the report.

Can this test be run as a SOQO re-query if my patient has previously been sequenced by Helix?

Yes. If a patient has been previously sequenced using the Helix Exome+ assay (for example, through WES+ or another Helix panel), the EDS panel can be run as a SOQO re-query without requiring a new sample. SOQO re-query turnaround time is typically 5 days or less.

Are medical records required to place an order?

Yes, we request that you provide relevant clinical notes with your order. They can be securely emailed to billing@helix.com or faxed to +1-858-777-3670.

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If your health system has the test built into your EHR, you can order it directly from there. Otherwise, you can use the Helix provider portal to place an order.

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