Ectodermal Dysplasia Panel
Test code: DE0401
The Blueprint Genetics Ectodermal Dysplasia Panel is a 19 gene test for genetic diagnostics of patients with clinical suspicion of Ellis-van Creveld syndrome, hidrotic ectodermal dysplasia or hypohidrotic ectodermal dysplasia.
EctodermaL dysplasia (ED) may present as isolated or syndromic disease and is subtyped commonly according to sweating ability. The clinical features of the X-linked and autosomal forms of hypohidrotic ectodermal dysplasia (HED) can be indistinguishable and many of the involved genes may lead to phenotypically distinct outcomes depending on number of defective alleles. HED can be clinically divided into more than 150 subtypes.
About Ectodermal Dysplasia
X-Linked hypohidrotic ectodermal dysplasia is caused by EDA mutations and explain 75%-95% of familial HED and 50% of sporadic cases. It is characterized by three cardinal features: hypotrichosis (sparse, slow-growing hair and sparse/missing eyebrows), reduced sweating and hypodontia (absence or small teeth). Reduced sweating pose risk for episodes of hyperthermia. Additionally, some degree of hypodontia and mild hypotrichosis can be seen in female carriers. Isolated dental phenotypes have also been described. Mutations in the WNT10A have been reported in up to 9% of individuals with HED and in 25% of individuals with HED who do not have defective EDA. Approximately 50% of individuals with heterozygous WNT10A mutation have HED and the most consistent clinical feature is severe oligodontia of permanent teeth. Mutations in the EDAR explain 7% of HED and associate to both autosomal dominant and recessive ED. This panel provide substantial differential diagnostics as it covers many syndromes that may present with ED. Several syndromes characterized by ED and hearing loss are associated with GJB2 mutations including KID syndrome, Vohwinkel syndrome, Bart-Pumphrey syndrome. Hidrotic ED type 2 is caused autosomal dominant GJB6 mutations and characterized by hypotrichosis, dysplastic nails and palmoplantar hyperkeratosis. Unlike other ectodermal dysplasias, sweating and tooth development are normal. Recessive EVC and EVC2 mutations associate with Ellis-van Creveld syndrome characterized by ED, dwarfism, polydactyly and heart defects but dominant mutations in the same genes associate with less severe Weyers acrofacial dysostosis. Expression of DSP-related ED is variable including woolly hair, alopecia, hyperkeratotic plaques, failure to thrive, neonatal teeth, dilated and arrhythmogenic right ventricular cardiomyopathy. The most severe presentation is lethal acantholytic epidermolysis bullosa. Prevalence of HED is estimated to be 1:5,000-10,000 newbornsa and Ellis-van Creveld syndrome 1:60,000 – 200,000.
Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal
|ABCC9||Atrial fibrillation, Cantu syndrome, Dilated cardiomyopathy (DCM)||AD||24||36|
|DSP||Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis, Arrhythmogenic right ventricular dysplasia, familial, Cardiomyopathy, dilated, with wooly hair and keratoderma||AD/AR||128||262|
|EDA||Ectodermal dysplasia, hypohidrotic, Tooth agenesis, selective||XL||91||316|
|EDAR||Ectodermal dysplasia, anhidrotic, Hair morphology||AD/AR||25||60|
|ERCC2||Xeroderma pigmentosum, Trichothiodystrophy, photosensitive||AR||22||86|
|EVC||Weyers acrofacial dysostosis, Ellis-van Creveld syndrome||AD/AR||11||80|
|EVC2||Ellis-van Creveld syndrome, Weyers acrodental dysostosis||AD/AR||26||67|
|GJB2||Deafness, Bart-Pumphrey syndrome, Keratoderma, palmoplantar, with deafness, Vohwinkel syndrome, Hystrix-like ichthyosis with deafness, Keratitis-icthyosis-deafness syndrome||AD/AR/Digenic||111||393|
|IFT122*||Sensenbrenner syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2||AR||11||17|
|IKBKG*||Incontinentia pigmenti, Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, Immunodeficiency, Invasive pneumococcal disease, recurrent, isolated, Osteopetrosis with ectodermal dysplasia and immune defect (OLEDAID)||XL||43||143|
|JUP||Arrhythmogenic right ventricular dysplasia, Naxos disease||AD/AR||8||38|
|PORCN||Focal dermal hypoplasia||XL||13||118|
|RMRP||Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia||AR||29||123|
|SHOC2||Noonan-like syndrome with loose anagen hair||AD||2||4|
|TP63||Rapp-Hodgkin syndrome, Orofacial cleft, ADULT syndrome, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome, Ankyloblepharon-ectodermal defects-cleft lip/palate, Split-hand/foot malformation, Limb-mammary syndrome||AD||52||114|
|WDR35||Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Short rib-polydactyly syndrome type 5||AR||19||28|
|WNT10A||Odontoonychodermal dysplasia, Tooth agenesis, selective, Schopf-Schulz-Passarge syndrome||AD/AR||17||73|
*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.
|Gene||Genomic location HG19||HGVS||RefSeq||RS-number|
The strengths of this test include:
- Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
- Superior sequencing quality
- Careful selection of genes based on current literature, our experience and the most current mutation databases
- Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
- Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
- Sequencing and high resolution del/dup analysis available in one test
- Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
- Interpretation of variants following ACMG variant classification guidelines
- Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist
This test does not detect the following:
- Complex inversions
- Gene conversions
- Balanced translocations
- Mitochondrial DNA variants
- Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.
This test may not reliably detect the following:
- Low level mosaicism
- Stretches of mononucleotide repeats
- Indels larger than 50bp
- Single exon deletions or duplications
- Variants within pseudogene regions/duplicated segments
- Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)
The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.
For additional information, please refer to the Test performance section and see our Analytic Validation.
Blueprint Genetics offers a comprehensive Ectodermal Dysplasia Panel that covers classical genes associated with Ellis-van Creveld syndrome, hidrotic ectodermal dysplasia and hypohidrotic ectodermal dysplasia. 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.
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. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. 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.
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.
Choose an analysis method
ICD & CPT codes
Commonly used ICD-10 codes when ordering the Ectodermal Dysplasia Panel
|Q82.4||Hypohidrotic ectodermal dysplasia|
|Q82.8||Hidrotic ectodermal dysplasia|
|Q77.6||Ellis-van Creveld 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.