Diagnostic Test Directory

Molecular Genetics Laboratory

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Craniofacial Panel (19 genes)



    Collect whole blood in a purple top (EDTA) tube(preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 8 ug extracted DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


6-8 weeks


81404(x3), 81405(x3), 81408, 81479(x12)

Disease Information

Clinical Features:

The craniofacial panel includes 19 genes that are known to be associated with disorders presenting with phenotypic features affecting head shape and/or facial appearance (see Molecular Genetics section for more details). The disorders covered in this panel include features such as craniosynostosis (the premature closure of cranial sutures resulting in a misshapen skull), cleft lip and/or palate, proptosis, and other features affecting the overall head and/or face. These features can present alone or as part of a larger collection of features resulting from a genetic mutation. The disorders included in this panel have variable expressivity making panel testing useful to pick up patients who may not present with the expected phenotype for a specific disorder. The main disease categories covered by this panel include craniosynostosis disorders, frontonasal dysplasia disorders, skeletal dysplasia disorders, and connective tissue disorders that may present with a craniofacial phenotype. Craniosynostosis disorders result in an abnormality in skull growth due to premature closure of cranial sutures. This premature closing can result in intracranial pressure that if untreated can cause permanent concerns for the patient. Frontonasal dysplasia disorders are defined by hypertelorism, broad nasal root, median facial clefting, lack of formation of the nasal tip, defect in the midline frontal skull bone, and a widow’s peak hairline. The skeletal dysplasia disorders are characterized by bone and cartilage growth abnormalities. Patients with a skeletal dysplasia may have differences in the growth of their legs, arms, trunk, and/or skull. The last grouping, connective tissue disorders, is defined by defects in a patient’s connective tissue which provides strength and flexibility throughout the body. These disorders may cause concerns for the bones, ligaments, muscles, and blood vessels. This results in various concerns for the patient that must be monitored. Some of the disorders within these four disease categories may overlap in phenotype as patients may present with variable phenotypes. (See Genes and Associated Syndromes Table)

Molecular Genetics:

The genes involved in the Craniofacial panel include ALX1, ALX3, ALX4, EFNB1, ERF, FBN1, FGFR1, FGFR2, FGFR3, GLI3, IFT122, MSX2, POR, RAB23, RECQL4, TCF12, TGFBR1, TGFBR2, and TWIST1. Multiple genes in this panel are involved in the FGFR signaling pathway which is known to be associated with craniosynostosis and skeletal dysplasias. Other genes in this panel are included in the TGF-beta signaling pathway which is associated with connective tissue disorders that may present with craniofacial findings. Mutations in these genes can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. (See Genes and Associated Syndromes Table for more details)

Test Methods:

Next Generation Sequencing for TWIST1, FBN1, RECQL4, MSX2, FGFR1, FGFR2, FGFR3, POR, GLI3, EFNB1, RAB23, TGFBR1, TGFBR2, IFT122, ALX1, ALX3, ALX4 Genomic DNA is extracted from blood or other patient tissues following standard DNA extraction protocols. This test is performed by next generation sequencing using the SureSelectXT Target Enrichment System (Agilent Inc) followed by Illumina MiSeq sequencing (2x 150bp paired end) of the coding regions and splice sites of the targeted genes. FASTQ data is de-multiplexed based on sample-specific index sequence using the MiSeq Reporter software and aligned to human reference genome hg19 using Novoalign. Variants are then called using the GATK pipeline and annotated using ANNOVAR and SnpEff. Sanger sequencing is performed to confirm clinically significant variants and to fill in regions with insufficient coverage (bases with less than 30X coverage). Variants that are classified as benign or likely benign will not be confirmed. Sanger s


Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.


The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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