Ehlers-Danlos Syndrome Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: CA0101

The Blueprint Genetics Ehlers-Danlos Syndrome Panel is a 33-gene test for genetic diagnostics of patients with clinical suspicion of Ehlers-Danlos syndrome.

Both autosomal dominant and recessive inheritance patterns are found among different forms of Ehlers-Danlos Syndrome (EDS). These inheritance patterns are also common in other disorders that overlap clinical features with EDS. Genetic diagnosis should be considered in all cases with suspicion of EDS or other disorder with similarities to EDS. Genetic diagnosis can confirm or modify the clinical diagnosis and also confirm the subtype of the disorder. Accurate diagnosis is essential when evaluating prognosis and making decisions on treatment and management strategies. Genetic diagnosis assists also genetic counseling, and risk stratification among family members.

About Ehlers-Danlos Syndrome

Ehlers–Danlos syndrome (EDS) is an inherited connective tissue disorder that has been classified into several primary types. EDS is caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen. The collagen in connective tissue helps tissues resist deformation. Collagen is an important contributor to the physical strength of skin, joints, ligaments, muscles, visceral organs and blood vessels. Defective collagen changes these structures more elastic. In some cases, the severity of the mutation can be life threatening. EDS can also have neuromuscular complications including ocular and ophthalmic complications. There is no cure for EDS, and treatment is supportive, including close monitoring of the digestive, excretory, and particularly the cardiovascular systems. Occupational and physical therapy, bracing, and corrective surgery may help with the frequent injuries and pain that tend to develop in certain types of EDS. There are several disorders that share some characteristics with EDS, such as cutis laxa where the skin is loose, hanging, and wrinkled. In EDS, the skin can be pulled away from the body but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile and similar cardiovascular complications occur. People with EDS tend to have a "Marfanoid" appearance (skinny, tall, long arms and legs, "spidery" fingers). However, physical appearance and features in several types of Ehlers-Danlos Syndrome also have characteristics including short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. Because of these similar disorders and complications that can arise from an unmonitored case of EDS, a correct diagnosis is very important. It is difficult to estimate the overall frequency of Ehlers-Danlos syndrome, however, the combined prevalence of all types of this condition may be about 1 in 5,000 individuals worldwide.

Availability

Results in 3-4 weeks.

Genes in the Ehlers-Danlos Syndrome Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ABCC6*Pseudoxanthoma elasticumAD/AR/Digenic39285
ADAMTS2Ehlers-Danlos syndromeAR311
ALDH18A1Spastic paraplegia, Cutis laxaAD/AR1825
ATP6V0A2Cutis laxa, Wrinkly skin syndromeAR1652
ATP7AMenkes diseaseXL105335
CBSHomocystinuria due to cystathionine beta-synthase deficiencyAR51192
CHST14Ehlers-Danlos syndrome, musculocontracturalAR1021
COL1A1Ehlers-Danlos syndromeAD120883
COL1A2Ehlers-Danlos syndrome, cardiac valvular formAD79473
COL2A1Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasiaAD106537
COL3A1Ehlers-Danlos syndromeAD452617
COL5A1Ehlers-Danlos syndromeAD43133
COL5A2Ehlers-Danlos syndromeAD1223
COL9A1AR34
COL9A2Stickler syndromeAR512
COL11A1Marshall syndrome, FibrochondrogenesisAD/AR1876
COL18A1Knobloch syndromeAR1329
EFEMP2Cutis laxaAR1115
ELNCutis laxa, Supravalvular aortic stenosisAD67104
FBLN5Cutis laxa, Macular degeneration, age-relatedAD/AR1321
FBN1MASS syndrome, Shprintzen-Goldberg syndrome, Marfan syndromeAD5192056
FBN2Congenital contractural arachnodactyly (Beals syndrome)AD3085
FKBP14Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing lossAR44
FLNAXL86209
PLOD1Ehlers-Danlos syndromeAR1637
PYCR1AR1234
SLC39A13Spondylodysplastic Ehlers-Danlos syndromeAR27
SMAD3Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndromeAD2650
TGFB2Loeys-Dietz syndromeAD1524
TGFBR1Loeys-Dietz syndromeAD2567
TGFBR2Loeys-Dietz syndromeAD54130
TNXB*Ehlers-Danlos syndromeAR826
ZNF469Brittle cornea syndromeAR3135
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive Ehlers-Danlos syndrome panel that covers classical genes associated with congenital contractural arachnodactyly, cutis laxa, Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Marfan syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the Ehlers-Danlos Syndrome Panel

ICD-10Disease
Q79.6Ehlers-Danlos syndrome

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.