• Test code: 04103
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Skeletal Ciliopathies Panel

Test description

The Invitae Skeletal Ciliopathies Panel analyzes up to 20 genes that have been shown to be important for the signaling function of primary cilia, a sensory organelle in the cell. These genes in particular are associated with a group of skeletal disorders, and were selected based on the currently available evidence in order to provide a comprehensive test for the diagnosis of these disorders.

The skeletal ciliopathies share many overlapping symptoms, which can make it difficult to distinguish between them. This panel test may be indicated for patients whose clinical features can be associated with one of several skeletal disorders, including short-rib thoracic dystrophy (SRTD), asphyxiating thoracic dystrophy (ATD), Ellis-van Creveld syndrome (EVC), Weyers acrofacial dysostosis (WAD), Mainzer-Saldino syndrome (MZSDS), oral-facial digital syndrome type IV (OFD IV) and cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (17 genes)


Add-on Skeletal Dysplasia Genes (3 genes)

Individuals with FGFR1, FGFR2, and FGFR3-related skeletal dysplasia may share clinical features with the skeletal ciliopathies. Given the significant overlap and the difficulty in differentiating between these disorders, analyzing these genes may be appropriate. These genes may be included at no additional charge.


Alternative tests to consider

Skeletal ciliopathies are part of a class of disorders called ciliopathies. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone. Depending on the individual’s clinical and family history, the broader Invitae Ciliopathies Panel may be appropriate. It can be ordered at no additional cost.

  • asphyxiating thoracic dystrophy (ATD)
  • cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome
  • Ellis–van Creveld syndrome (EVC)
  • Mainzer–Saldino syndrome (MZSDS)
  • oral-facial-digital syndrome 4 (OFD IV)
  • short rib thoracic dystrophy (STRD)
  • short rib polydactyly syndromes (SRPS)
  • Weyers acrofacial dysostosis (WAD)

The skeletal ciliopathies, which include short-rib thoracic dystrophy (SRTD), asphyxiating thoracic dystrophy (ATD), Ellis-van Creveld syndrome (EVC), Weyers acrofacial dysostosis (WAD), Mainzer-Saldino syndrome (MZSDS), oral-facial digital syndrome type IV (OFD IV) and cranioectodermal dysplasia (CED), are a group of skeletal disorders caused by mutations in genes important for ciliary structure and/or function. They are generally characterized by skeletal anomalies, such as constricted rib cages and/or shortened long bones, along with variable extra-skeletal organ involvement. Polydactyly may or may not be present. While there is broad clinical overlap among these conditions, they may differ in severity and major organ involvement. SRPS types I-V are perinatal lethal, whereas EVC, WAD, ATD, CED, OFD IV, and MZSDS can be compatible with life (PMID: 23910462). Non-skeletal features may include cleft lip/palate, dental abnormalities, brain anomalies, retinal degeneration, heart defects, cystic kidneys, liver disease, pancreatic cysts, and abnormality of the genitalia (PMID: 22791528, 23910462, 24183449).

DisordersClinical sensitivity
cranioectodermal dysplasia (CED) 40%
Ellis–van Creveld syndrome (EVC) and Weyers acrofacial dysostosis (WAD) 85%
Mainzer–Saldino syndrome (MZSDS) 50%
oral-facial digital syndrome type IV (OFD IV) 50%
short rib thoracic dystrophy (SRTD) and asphyxiating thoracic dystrophy (ATD) ~50%

The ciliary chondrodysplasias are inherited in an autosomal recessive manner, with the exception of Weyers acrofacial dysostosis, which is autosomal dominant.

The ciliary chondrodysplasias are highly penetrant but exhibit wide variability in the age of onset and severity of disease, even within families.

The ciliary chondrodysplasias are rare disorders with a collective prevalence estimated between 1:200,000 to 1:1,000,000. The prevalence is higher in populations that are isolated or have high rates of consanguinity.

The main characteristics of a patient for whom this test would be appropriate for include:

  • narrow thorax with shortened ribs
  • short stature
  • variable polydactyly
  • brachydactyly
  • shortened limbs

  1. Huber, C, et al. WDR34 mutations that cause short-rib polydactyly syndrome type III/severe asphyxiating thoracic dysplasia reveal a role for the NF-κB pathway in cilia. Am. J. Hum. Genet. 2013; 93(5):926-31. PMID: 24183449
  2. Arts, H, Knoers, N. Cranioectodermal Dysplasia. 2013 Sep 12. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK154653/ PMID: 24027799
  3. Lin, AE, et al. Sensenbrenner syndrome (Cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients. Am. J. Med. Genet. A. 2013; 161A(11):2762-76. PMID: 24123776
  4. Oberklaid, F, et al. Asphyxiating thoracic dysplasia. Clinical, radiological, and pathological information on 10 patients. Arch. Dis. Child. 1977; 52(10):758-65. PMID: 931421
  5. McInerney-Leo, AM, et al. Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60. Am. J. Hum. Genet. 2013; 93(3):515-23. PMID: 23910462
  6. D'Asdia, MC, et al. Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis. Eur J Med Genet. 2013; 56(2):80-7. PMID: 23220543
  7. Perrault, I, et al. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations. Am. J. Hum. Genet. 2012; 90(5):864-70. PMID: 22503633
  8. Huber, C, Cormier-Daire, V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012; 160C(3):165-74. PMID: 22791528
  9. Thomas, S, et al. TCTN3 mutations cause Mohr-Majewski syndrome. Am. J. Hum. Genet. 2012; 91(2):372-8. PMID: 22883145
  10. Valencia, M, et al. Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Hum. Mutat. 2009; 30(12):1667-75. PMID: 19810119
  11. Tompson, SW, et al. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. Hum. Genet. 2007; 120(5):663-70. PMID: 17024374

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
CEP120 NM_153223.3
CSPP1 NM_024790.6
DYNC2H1 NM_001080463.1
EVC NM_153717.2
EVC2 NM_147127.4
FGFR1 NM_023110.2
FGFR2 NM_000141.4
FGFR3 NM_000142.4
IFT122 NM_052985.3
IFT140 NM_014714.3
IFT172 NM_015662.2
IFT80 NM_020800.2
KIAA0586 NM_001244189.1
NEK1 NM_012224.2
TCTN3 NM_015631.5
TTC21B NM_024753.4
WDR19 NM_025132.3
WDR34 NM_052844.3
WDR35 NM_001006657.1
WDR60 NM_018051.4