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Ehlers-Danlos Syndrome Panel

The Ehlers-Danlos Syndrome Panel is a comprehensive next-generation (NGS) panel that can be used to confirm a clinical diagnosis of Ehlers-Danlos syndrome or identify or at-risk individuals.

Ehlers-Danlos syndrome is a heterogenous group of connective tissue disorders that affect the skin, joints, ligaments, blood vessels, and internal organs. Clinical features of Ehlers-Danlos syndrome include joint hypermobility, skin hyperextensibility, and abnormal wound healing. Individuals with Ehlers-Danlos syndrome are at risk for mitral and tricuspid valve prolapse, aortic root dilatation, and rupture of the large arteries. The clinical features of the condition vary greatly between individuals, and several clinical subtypes have been described. Individuals with Ehlers-Danlos syndrome are at risk for sudden death due to rupture of major blood vessels, and some individuals may be at risk for life-threatening pregnancy complications.

Included Disorders

This panel includes genes associated with:

  • Ehlers-Danlos syndrome
  • Osteogenesis imperfecta
  • Occipital horn syndrome
  • Menkes syndrome

Prevalence

The prevalence of Ehlers-Danlos syndrome is approximately 1 in 20,000 individuals (Byers, 2001), although it may be more common in some populations.

Inheritance and Penetrance:

Ehlers-Danlos syndrome and related conditions are inherited in autosomal dominant, autosomal recessive, and X-linked manners. Penetrance is typically high, with variable expressivity.

Clinical Sensitivity

A pathogenic variant can be identified in 50-90% of classic Ehlers-Danlos cases, and in 95% of vascular Ehlers-Danlos cases (Mayer et al, 2012). The clinical sensitivity of genetic testing for individuals with rarer forms of Ehlers-Danlos syndrome or without a specific diagnosis is unknown.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity and specificity of the assay is >99%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Personal or family history of an aortic aneurysm or dissection
  • Risk assessment for asymptomatic family members of proband with molecular diagnosis

Included Genes (14)

ADAMTS2 CHST14 COL1A2 COL5A1 CRTAP FLNA PLOD1
ATP7A COL1A1 COL3A1 COL5A2 FKBP14 P3H1 SLC39A13
Additions to Comprehensive Panel

Emerging evidence genes can also be added onto the Ehlers-Danlos Syndrome Panel. These genes do not have a clear association with Ehlers-Danlos syndrome, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence Gene (1)

MAT2A

 

References

  1. Byers PH. Disorders of collagen biosynthesis and structure. In: Scriver, Beaudet, Sly, Valle, eds. The Metabolic and Molecular Bases of Inherited Disease. 2 ed. Edinburgh, UK: Churchill Livingstone; 2001:1065-81.
  2. Mayer K, Kennerknecht I, Steinmann B. Clinical utility gene card for: Ehlers-Danlossyndrome types I-VII and variants – update 2012. Eur J Hum Genet. 2013;21(1)