Genetics of Ehlers-Danlos Syndrome Workup

Updated: Apr 07, 2021
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

The following laboratory studies may be indicated in patients diagnosed with Ehlers-Danlos syndrome (EDS):

  • Diagnosis of the vascular-type EDS (type IV), arthrochalasia-type EDS (types VIIA and VIIB), and dermatosparaxis-type EDS (type VIIC) requires a skin biopsy. Biochemical studies performed on cultured skin fibroblasts can detect alterations in collagen molecules.

  • Molecular (DNA-based) testing is available for the vascular, arthrochalasia, and dermatosparaxis types.

  • Kyphoscoliosis-type EDS (type VI) can be identified by urine enzyme assay.

The remaining types of EDS—classical-type EDS and hypermobility-type EDS—are diagnosed through clinical examination.

A multi-institutional, cross-sectional, retrospective study by Shalhub et al demonstrated the pitfalls of using clinical criteria alone in diagnosing vascular-type EDS. Patients who were diagnosed only through clinical evaluation had a higher rate of symptoms characteristic of other forms of EDS, specifically, mitral valve prolapse and joint hypermobility, than did patients whose diagnosis was confirmed via testing for pathogenic COL3A1 variants (10.5% vs 1.2% and 68.4% vs 40.7%, respectively). The clinical diagnosis–only cohort also had a lower rate of symptoms characteristic of vascular-type EDS than did the genetic-testing group, including easy bruising (23.7% vs 64%, respectively), thin translucent skin (17.1% vs 48.8%, respectively), intestinal perforation (3.9% vs 16.3%, respectively), spontaneous pneumothorax/hemothorax (3.9% vs 14%, respectively), and arterial rupture (9.2% vs 17.4%, respectively). [33]



Imaging Studies

Patients diagnosed with vascular-type Ehlers-Danlos syndrome (type IV) have positive findings on various imaging studies, namely computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, ultrasonography, and angiography. The most common imaging abnormalities are arterial aneurysms and arterial dissections, followed by arterial ectasias and arterial occlusions. [34]


Other Tests

Ultrastructural examination of collagen fibrils may be a useful diagnostic tool to support the diagnosis of classical-type Ehlers-Danlos syndrome (EDS) (types I and II), but also for arthrochalasia-type EDS (types VIIA and VIIB) and to help further differentiate subtype VIIA from subtype VIIB. [35]


Histologic Findings

Presently, histopathologic analyses of skin biopsy specimens are nondiagnostic.