• Test code: 04423
  • 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

Invitae Craniosynostosis Panel

Test description

The Invitae Craniosynostosis Panel analyzes up to 11 genes that are associated with isolated and syndromic forms of craniosynostosis. These genes were selected based on the available evidence to date.

Genetic testing can provide an accurate diagnosis, which may help guide medical management and surveillance decisions, predict disease progression and outcome, and indicate the recurrence risk.

Order test

Primary panel (9 genes)


Add-on 3MC and Treacher-Collins Syndrome Genes (2 genes)

Craniosynostosis is a prominent feature in 3MC syndrome (MASP1) and Treacher Collins syndrome (TCOF1). If clinically indicated, clinicians can choose to include these genes at no additional charge.


Craniosynostosis occurs when one or more sutures in the skull prematurely fuse before the brain has finished growth and development. Craniosynostosis affects the shape of the head and facial features and exhibits variable clinical severity. The majority of craniosynostosis occurs as an isolated feature and is characterized by which sutures have fused. Craniosynostosis may also be one feature of a broader syndromic condition that affects other organ systems; some such conditions are commonly associated with hearing loss, hand or foot abnormalities, brain malformations, and cardiac and genitourinary anomalies.

The clinical sensitivity of FGFR-related craniosynostosis is 100%. Clinical sensitivity of GLI3-related Greig cephalopolysyndactyly syndrome is approximately 75% and TWIST1-related Saethre-Chotzen syndrome is approximately 68%. The clinical sensitivity for the remaining genes in this panel is not well-established.

Craniosynostosis is generally inherited in an autosomal dominant manner. MASP1-related craniosynostosis, however, is inherited in an autosomal recessive pattern.

TWIST1 demonstrates incomplete penetrance. Penetrance for FGFR-related craniosynostosis varies amongst syndromes. FGFR-related coronal synostosis has reduced penetrance. Jackson-Weiss, Apert, Crouzon, and Pfeiffer syndromes typically demonstrate complete penetrance. Penetrance for craniosynostosis related to the remaining genes on this panel is unknown at this time.

Prevalence of craniosynostosis is 1 in 200 to 1 in 2500 live births.

This panel may be appropriate for individuals with a diagnosis of craniosynostosis—with or without additional features—to identify a hereditary cause of disease.

  1. Bowman, M, et al. Gross deletions in TCOF1 are a cause of Treacher-Collins-Franceschetti syndrome. Eur. J. Hum. Genet. 2012; 20(7):769-77. PMID: 22317976
  2. Ignelzi, MA, et al. Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. J. Bone Miner. Res. 2003; 18(4):751-9. PMID: 12674336
  3. Dollfus, H, et al. Saethre-Chotzen syndrome: notable intrafamilial phenotypic variability in a large family with Q28X TWIST mutation. Am. J. Med. Genet. 2002; 109(3):218-25. PMID: 11977182
  4. de, Heer, IM, et al. Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. Plast. Reconstr. Surg. 2005; 115(7):1894-902; discussion 1903-5. PMID: 15923834
  5. Agochukwu, NB, et al. Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses. Childs Nerv Syst. 2012; 28(9):1447-63. PMID: 22872262
  6. Governale, LS. Craniosynostosis. Pediatr. Neurol. 2015; 53(5):394-401. PMID: 26371995
  7. Passos-Bueno, MR, et al. Genetics of craniosynostosis: genes, syndromes, mutations and genotype-phenotype correlations. Front Oral Biol. 2008; 12:107-43. PMID: 18391498
  8. Robin, NH, et al. FGFR-Related Craniosynostosis Syndromes. 1998 Oct 20. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301628
  9. Gallagher, ER, et al. Saethre-Chotzen Syndrome. 2003 May 16. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301368
  10. Biesecker, LG. Greig Cephalopolysyndactyly Syndrome. 2001 Jul 09. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301619

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
ERF NM_006494.3
FGFR1 NM_023110.2
FGFR2 NM_000141.4
FGFR3 NM_000142.4
GLI3 NM_000168.5
MASP1 NM_139125.3
MEGF8 NM_001410.2
MSX2 NM_002449.4
RAB23 NM_183227.2
TCOF1 NM_001135243.1
TWIST1 NM_000474.3