The vascular form of Ehlers-Danlos syndrome (vEDS) is characterized by thin, translucent skin with visible veins; marked bruising; joint dislocations; and the major complications of arterial, bowel and uterine rupture.
The vast majority of probands in families with this form of EDS are identified on the basis of a major complication either bowel perforation or vascular aneurysm or rupture. The International Ehlers-Danlos Foundation Advisory Board set the following guidelines for determination of the clinical diagnosis of EDS type IV. DNA-based testing is recommended for those who meet these guidelines. Note, however, that individuals with nonsense mutations of COL3A1 are less likely to have similar physical characteristics. The clinical diagnosis of EDS type IV is highly suspected when two major diagnostic criteria are present:
Major clinical diagnostic criteria:
- Intestinal rupture
- Arterial rupture
- Uterine rupture during pregnancy
- Family history of the vascular type of EDS
Minor diagnostic criteria alone are not sufficient to warrant the diagnosis unless identified in an individual with a major criteria.
- Thin, translucent skin (especially noticeable on the chest/abdomen)
- Easy bruising (spontaneous or with minimal trauma)
- Characteristic facial appearance (thin lips and philtrum, small chin, thin nose, large eyes)
- Acrogeria (an aged appearance to the extremities, particularly the hands)
- Hypermobility of small joints
- Tendon/muscle rupture
- Early-onset varicose veins
- Arteriovenous carotid-cavernous sinus fistula
- Chronic joint subluxations/dislocations
- Congenital dislocation of the hips
- Talipes equinovarus (clubfoot)
- Gingival recession
Please consult the Ehlers-Danlos Syndrome Test Guide for more information on the diagnosis.
Next Generation Sequencing: Next generation DNA sequencing is performed to identify nucleotide variants in the coding portion of the genome. All nucleotides in the coding exons and their flanking splice junctions are sequenced to a read coverage of greater than 20X. The sequence data are assembled and compared to the published genomic reference sequence. Sanger sequencing is performed if necessary to ensure complete nucleotide coverage of the target sequence and to confirm all reported variants. Human Genome Variation Society (HGVS) recommendations are followed for variant nomenclature and ACMGG/AMP variant interpretation guidelines are followed to assess variant pathogenicity, unless otherwise indicated. The following online databases and in silico analysis tools are routinely used for variant investigation: ClinVar, NHLBI Exome Sequencing Project, 1000 Genomes, dbSNP, Exome Aggregation Consortium (ExAC), available loci specific variant databases, PolyPhen-2, SIFT, Provean, Mutation Taster and Human Splicing Finder.
BLOOD IS PREFERRED.
BLOOD: 2 EDTA (purple top) tubes
Whole blood may be stored up to 5-7 days in the refrigerator before shipping.
5 µg DNA at a minimum concentration of ≥200 ng/µl
Oragene Saliva samples are accepted
Amniocytes or Cultured CVS Cells: Two confluent T-25 flasks of cultured amniocytes or CVS cells, well-labeled as Prenatal Sample. Please call ahead to notify the CDL that a prenatal sample will be coming.
Blood samples (or DNA) should be well labeled with patient’s full name and an identifying number.
Ship sample at room temperature with overnight delivery.
Clinical information outlining the indication for the requested tests and pertinent medical history and family history is a necessary component of testing. Please include a clinic note when available.
Reflex to Deletion/Duplication Studies: The Collagen Diagnostic Laboratory offers testing for copy number changes using a custom high-density targeted oligonucleotide array for these genes for an additional charge. The targeted regions have probe coverage in both the coding sequences and 10 kb upstream of the gene(s) of interest.
CPT Code & Cost81479