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.

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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. 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
  2. Biesecker, LG. Greig Cephalopolysyndactyly Syndrome. 2001 Jul 09. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301619
  3. 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
  4. 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
  5. Gallagher, ER, et al. Saethre-Chotzen Syndrome. 2003 May 16. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301368
  6. Governale, LS. Craniosynostosis. Pediatr. Neurol. 2015; 53(5):394-401. PMID: 26371995
  7. 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
  8. Passos-Bueno, MR, et al. Genetics of craniosynostosis: genes, syndromes, mutations and genotype-phenotype correlations. Front Oral Biol. 2008; 12:107-43. PMID: 18391498
  9. 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
  10. 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

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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