Ectodermal Dysplasia Panel

Last modified: Mar 21, 2018


  • Is a 23 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion of ectodermal dysplasia (hidrotic or hypohidrotic) or Ellis-van Creveld syndrome.

Analysis methods

  • PLUS
  • SEQ


3-4 weeks

Number of genes


Test code


CPT codes

SEQ 81252
SEQ 81405
SEQ 81406
DEL/DUP 81479


The Blueprint Genetics Ectodermal Dysplasia Panel (test code DE0401):

  • Is a 23 gene panel that includes assessment of selected non-coding disease-causing variants
  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

ICD codes

Commonly used ICD-10 code(s) when ordering the Ectodermal Dysplasia Panel

ICD-10 Disease
Q82.4 Hypohidrotic ectodermal dysplasia
Q82.8 Hidrotic ectodermal dysplasia
Q77.6 Ellis-van Creveld syndrome

Sample Requirements

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 3μg
  • 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.

Ectodermal Dysplasia (ED) is a group of closely related conditions of which more than 150 different syndromes have been identified. EDs affects the development or function of teeth, hair, nails and sweat glands. ED may present as isolated or as part of a syndromic disease and is commonly subtyped 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. The most common EDs are hypohidrotic ED and hydrotic ED. X-linked hypohidrotic ectodermal dysplasia (HED) is caused by EDA mutations and explain 75%-95% of familial HED and 50% of sporadic cases. HED 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 poses risk for episodes of hyperthermia. Female carriers may have some degree of hypodontia and mild hypotrichosis. Isolated dental phenotypes have also been described. Mutations in 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 EDAR explain 7% of HED and are associated with both autosomal dominant and recessive ED. This panel provide differential diagnostic power 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 by 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 cause Ellis-van Creveld syndrome characterized by ED, dwarfism, polydactyly and heart defects, however, dominant mutations in the same genes cause the less severe Weyers acrofacial dysostosis. Expression of DSP-related ED is variable including woolly hair, alopecia, hyperkeratotic plaques, failure to thrive, dilated and arrhythmogenic right ventricular cardiomyopathy. The most severe presentation is lethal acantholytic epidermolysis bullosa. The prevalence of HED is estimated to be 1:5,000-10,000 newborns while that of Ellis-van Creveld syndrome is 1:60,000 – 200,000.

Genes in the Ectodermal Dysplasia Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
BCS1L Bjornstad syndrome AR 32 37
CDH3 Hypotrichosis, congenital, with juvenile macular dystrophy, Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome AR 6 29
DSP Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis, Arrhythmogenic right ventricular dysplasia, familial, Cardiomyopathy, dilated, with wooly hair and keratoderma, Keratosis palmoplantaris striata II, Epidermolysis bullosa, lethal acantholytic AD/AR 128 262
EDA Ectodermal dysplasia, hypohidrotic, Tooth agenesis, selective XL 91 316
EDAR Ectodermal dysplasia, anhidrotic, Hair morphology AD/AR 25 60
EDARADD Ectodermal dysplasia, anhidrotic, autosomal recessive, Ectodermal dysplasia, anhidrotic, autosomal dominant, Ectodermal dysplasia, hypohidrotic, autosomal dominant, Ectodermal dysplasia, hypohidrotic, autosomal recessive AD/AR 6 10
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
GJB6 Deafness AR/Digenic 9 28
HOXC13 Ectodermal dysplasia 9 AR 3 9
HR Hypotrichosis 4, Atrichia with papular lesions, Alopecia universalis congenita AD/AR 14 52
IFT122* Sensenbrenner syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2 AR 11 17
JUP Arrhythmogenic right ventricular dysplasia, Naxos disease AD/AR 8 38
LRP6 Tooth agenesis, selective, 7 AD 18 29
MPLKIP Trichothiodystrophy 4, nonphotosensitive AR 8 17
PORCN Focal dermal hypoplasia XL 13 118
PRKD1 Congenital heart defects and ectodermal dysplasia 2 6
RMRP Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia AR 29 123
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, or all, of the gene is duplicated in the genome. Read more.

# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Orphanet databases.

Non-coding variants covered by the panel

Gene Genomic location HG19 HGVS RefSeq RS-number
BCS1L Chr2:219524871 c.-147A>G NM_004328.4
BCS1L Chr2:219525123 c.-50+155T>A NM_004328.4 rs386833855
EDA ChrX:69249341 c.707-13T>C/G NM_001399.4
EVC Chr4:5749725 c.940-150T>G NM_153717.2
GJB2 Chr13:20763744 c.-22-2A>C NM_004004.5 rs201895089
GJB2 Chr13:20766921 c.-23+1G>A NM_004004.5 rs80338940
GJB2 Chr13:20766922 c.-23G>T NM_004004.5 rs786204734
GJB2 Chr13:20767158 c.-259C>T NM_004004.5
GJB2 Chr13:20767159 c.-260C>T NM_004004.5
PORCN ChrX:48370699 c.374-15G>A NM_203475.1
PORCN ChrX:48370668 c.374-46T>A NM_203475.1
RMRP Chr9:35657745 NR_003051.3 rs377349293
RMRP Chr9:35657746 NR_003051.3 rs551655682
WDR35 Chr2:20182313 c.143-18T>A NM_001006657.1
WDR35 Chr2:20151929 c.1434-684G>T NM_001006657.1

Added and removed genes from the panel

Genes added Genes removed

Test strength

The strengths of this test include:
  • CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • Our publically available analytic validation demonstrating complete details of test performance
  • 1479 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification based on modified ACMG variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test limitations

Genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:
  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

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

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.

The Blueprint Genetics ectodermal dysplasia panel covers classical genes associated with hypohidrotic ectodermal dysplasia, hidrotic ectodermal dysplasia and Ellis-van Creveld syndrome. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).

Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics' Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient's phenotype is suggestive of a specific mutation type.

Performance of Blueprint Genetics Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.65% (412,456/413,893) >99.99%
Insertions, deletions and indels by sequence analysis
1-10 bps 96.94% (17,070/17,608) >99.99%
11-50 bps 99.07% (957/966) >99.99%
Copy number variants (exon level dels/dups)
Clinical samples (small CNVs, n=52)
1 exon level deletion 92.3% (24/26) NA
2 exons level deletion/duplication 100.0% (11/11) NA
3-7 exons level deletion/duplication 93.3% (14/15) NA
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
Simulated CNV detection
2 exons level deletion/duplication 90.98% (7,357/8,086) 99.96%
5 exons level deletion/duplication 98.63% (7,975/8,086) 99.98%
The performance presented above reached by WES with the following coverage metrics
Mean sequencing depth at exome level 174x
Nucleotides with >20x sequencing coverage (%) 99.4%


The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. 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. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases such as, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to crucial details of the analysis process.

Clinical interpretation

We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.

Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen less than three times at Blueprint Genetics.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references used, congress abstracts and mutation databases to help our customers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling. For eligible cases, Blueprint Genetics offers a no charge service to investigate the role of reported VUS (VUS Clarification Service).

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. Our laboratory is therefore well positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.