Guidelines for Laboratory Testing for EHLERS-DANLOS SYNDROME

  1. The CDL offers limited diagnostic testing for EDS. If your patient has clinical features of vascular EDS (EDS type IV) or arthrochalasia (EDS type VII), Collagen Screening Studies will identify the vast majority of affected individuals. (References: Pepin 2000, Byers 1997). The sensitivity of collagen screening is greater than 95%.

  2. Vascular EDS testing can also be completed by requesting COL3A1 Genomic DNA Sequencing from blood. The sensitivity of COL3A1 sequencing is expected to be similar or slightly better than collagen screening.

  3. If collagen screening studies are requested and the biochemical results are consistent with vascular EDS, cDNA sequencing will be initiated automatically to confirm the diagnosis. In these instances cDNA sequencing is completed on the segments of the COL3A1 cDNA suspected to house the mutation based on collagen testing.

  4. If your patient has a family history of vascular EDS confirmed by a COL3A1 mutation, DNA testing of blood for family members is available.

  5. If your patient has the clinical features of classical EDS, the most accurate means to confirm the diagnosis is examination by a clinical geneticist. The CDL offers collagen screening to exclude the diagnosis of EDS type IV.  COL5A1 and COL5A2 molecular testing is not available through the Collagen Diagnostic Laboratory.

  6. If your patient has congenital hypotonia, soft hyperextensible skin and scoliosis as primary features, we recommend that you consider the diagnosis of lysyl-hydroxylase deficiency. A urine screen for the accumulation of pyridinoline cross-links is available as a screening test in other laboratories (Reference: GeneTests Laboratory Directory).

  7. If your patient has a variety of connective tissue abnormalities including enlargement or aneurysm of the aortic root, you may want to consider requesting DNA testing from blood for Transforming Growth Factor Beta receptor (TGRBR1/2) gene mutations. A large proportion of individuals with mutations in the TBFBR1/2 genes have abnormalities in the formation of the uvula including bifid or broad uvula. Congenital heart disease, craniofacial abnormalities and neuro-cognitive problems have also been described in this newly identified syndrome (Reference: Loeys 2005).

  8. If your patient has only a few features of a connective tissue disorder and you are considering the clinical diagnosis of EDS, you may want to contact the genetic counselors, Melanie Pepin or Dru Leistritz, or Dr. Peter Byers to determine the usefulness of CDL lab testing for your patient. The clinical features of many forms of Ehlers Danlos syndrome are outlined in the EDS Table (Reference: Byers & Schwarze 2001)