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  • Test code: 05021
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Ectodermal Dysplasia with or without Tooth Agenesis Panel

Test description

The Invitae Ectodermal Dysplasia with or without Tooth Agenesis Panel analyzes up to 10 genes that are important for the development or function of ectodermal tissues including skin, hair, teeth, nails, and sweat glands. These genes are associated with a group of conditions known as ectodermal dysplasias (ED) with or without tooth agenesis and were selected, based on the available evidence to date, to provide a comprehensive test for the diagnosis of these disorders.

Ectodermal dysplasias share overlapping features, which can make it difficult to distinguish between them based on clinical findings alone. This panel may confirm a genetic diagnosis without the need for sequential gene testing. Identification of a disease-causing variant would help guide treatment and management decisions as well as inform recurrence-risk assessment and genetic counseling.

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Primary panel (8 genes)

EDA EDAR EDARADD LTBP3 MSX1 NFKBIA PAX9 WNT10A

Add-on Clouston Syndrome and TP63-related Disorder Genes (2 genes)

Ectodermal dysplasia is a shared feature observed in Clouston syndrome (GJB62) and TP63-related disorders. In addition to ectodermal dysplasia, Clouston syndrome is also characterized by palmoplantar hyperkeratosis. TP63-related disorders represent a class of overlapping phenotypes that share a common spectrum of features including variable forms of ectodermal dysplasia, cleft lip/palate, hypopigmented skin, split-hand/foot malformation and/or syndactyly, and hypoplasia of the breasts and/or nipples. Depending on the clinical presentation of the patient, clinicians may wish to broaden analysis by including these genes at no additional charge.

GJB6 TP63

  • anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis and lymphedema (OLEDAID)
  • anhidrotic ectodermal dysplasia with T-cell immunodeficiency (EDA-ID)
  • hypohidrotic ectodermal dysplasia
    • autosomal recessive hypohidrotic ectodermal dysplasia
    • autosomal dominant hypohidrotic ectodermal dysplasia
    • X-linked hypohidrotic ectodermal dysplasia
  • LTBP3-related dental anomalies
  • odonto-onycho-dermal dysplasia
  • PAX9-related tooth agenesis
  • Witkop syndrome
  • WNT10A-related ectodermal dysplasia and tooth agenesis

Ectodermal dysplasia (ED) is characterized by sparse hair, atypical shape or absence of teeth, and abnormal development of sweat glands that results in a reduced ability to sweat. The clinical features of ectodermal dysplasia are variable. Some individuals present early in life with fragile skin or hair, absent or delayed eruption of teeth, and heat intolerance; others may only have mild symptoms or isolated tooth agenesis. Female carriers of X-linked ectodermal dysplasia and individuals with autosomal dominant ectodermal dysplasia are more likely to have milder clinical findings, although clinical variability is also observed in males with X-linked ED and often are indistinguishable based on inheritance pattern alone.

Tooth agenesis is a clinical feature that is often seen in individuals with ectodermal dysplasias, though it may also present as an isolated finding or in combination with other features, such as orofacial clefting and short stature. Tooth agenesis may present with normal hair development and the ability to sweat.

Pathogenic variants in EDA1 account for the majority (55%-60%) of clinically diagnosed cases of ectodermal dysplasia. The proportion of ectodermal dysplasia with or without tooth agenesis attributed to pathogenic variants in the remaining genes on this panel. See table below for details.

GeneProportion of ED attributed to pathogenic variants in this gene
EDA 55% – 60%
EDAR 15% – 20%
EDARADD 1% – 2%
LTBP3 unknown
MSX1 unknown
NFKBIA unknown
PAX9 unknown
WNT10A 9%

Ectodermal dysplasias can be inherited in several patterns, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive.

EDA-related ectodermal dysplasia is highly penetrant (>70%). Penetrance for other forms of ED is uncertain.

The prevalence of ectodermal dysplasia is estimated at 1 in 5000–10,000 individuals. Tooth agenesis is relatively common with most studies reporting a prevalence between 6-8%.

This test may be considered for individuals who have sparseness of scalp and body hair, reduced ability to sweat, and congenital absence of teeth.

  1. Cluzeau, C, et al. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum. Mutat. 2011; 32(1):70-2. PMID: 20979233
  2. Chassaing, N, et al. Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia. Hum. Mutat. 2006; 27(3):255-9. PMID: 16435307
  3. Wright, JT, et al. Hypohidrotic Ectodermal Dysplasia. 2003 Apr 28. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301291
  4. Bohring, A, et al. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am. J. Hum. Genet. 2009; 85(1):97-105. PMID: 19559398
  5. Adaimy, L, et al. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am. J. Hum. Genet. 2007; 81(4):821-8. PMID: 17847007
  6. Lidral, AC, Reising, BC. The role of MSX1 in human tooth agenesis. J. Dent. Res. 2002; 81(4):274-8. PMID: 12097313
  7. Jumlongras, D, et al. A nonsense mutation in MSX1 causes Witkop syndrome. Am. J. Hum. Genet. 2001; 69(1):67-74. PMID: 11369996
  8. van, den, Boogaard, MJ, et al. MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. Nat. Genet. 2000; 24(4):342-3. PMID: 10742093
  9. Mostowska, A, et al. A novel mutation in PAX9 causes familial form of molar oligodontia. Eur. J. Hum. Genet. 2006; 14(2):173-9. PMID: 16333316
  10. Lammi, L, et al. A missense mutation in PAX9 in a family with distinct phenotype of oligodontia. Eur. J. Hum. Genet. 2003; 11(11):866-71. PMID: 14571272
  11. Huckert, M, et al. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta. Hum. Mol. Genet. 2015; 24(11):3038-49. PMID: 25669657
  12. Dugan, SL, et al. New recessive truncating mutation in LTBP3 in a family with oligodontia, short stature, and mitral valve prolapse. Am. J. Med. Genet. A. 2015; 167(6):1396-9. PMID: 25899461
  13. Lamartine, J, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat. Genet. 2000; 26(2):142-4. PMID: 11017065
  14. Nemoto-Hasebe, I, et al. Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss. Br. J. Dermatol. 2009; 161(2):452-5. PMID: 19416251
  15. Andrade, AC, et al. Clouston syndrome associated with eccrine syringofibroadenoma. An Bras Dermatol. 2014; 89(3):504-6. PMID: 24937830
  16. Rinne, T, et al. p63-associated disorders. Cell Cycle. 2007; 6(3):262-8. PMID: 17224651
  17. Sutton, VR, van, Bokhoven, H. TP63-Related Disorders. 2010 Jun 08. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20556892

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
EDA NM_001399.4
EDAR NM_022336.3
EDARADD NM_145861.2
GJB6 NM_006783.4
LTBP3 NM_001130144.2
MSX1 NM_002448.3
NFKBIA NM_020529.2
PAX9 NM_006194.3
TP63 NM_003722.4
WNT10A NM_025216.2