Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
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.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
The craniosynostosis (CSS) syndromes are a genetically heterogeneous group of disorders characterized by premature fusion of sutures of the skull. The clinical features of CSS often overlap and vary in terms of complexity and severity. Clinical features that may be observed in association with craniosynostosis include developmental delay, seizures, hand and foot anomalies, and characteristic facial features [GeneReviews 2020, PMID: 20301628].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for the Craniosynostosis panel is not yet well established and can depend on the patient's clinical features. The genes that are expected to have the highest yield of disease-causing variants are FGFR2, FGFR3, TWIST1, and EFNB1. Copy number variants have been reported in most of the genes on this panel, although they are typically significantly less common than pathogenic sequence variants in these genes.
Utility
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. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Craniosynostosis panel V2 includes genes known to be associated with craniosynostosis and related genetic disorders such as Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, Jackson-Weiss syndrome, Muenke syndrome, isolated coronal synostosis, Saethre-Chotzen syndrome, Antley-Bixler syndrome, Baller-Gerold syndrome, Carpenter syndrome, cranioectodermal dysplasia, and Shprintzen-Goldberg syndrome. The following genes are included: ALPL, ASXL1, CD96, CDC45, CYP26B1, EFNB1, ERF, FGFR1, FGFR2, FGFR3, IFT122, IFT43, IL11RA, MASP1, MEGF8, MSX2, POR, RAB23, RECQL4, RUNX2, SKI, SLC25A24, SMAD6, SPECC1L, TCF12, TGFBR1, TGFBR2, TWIST1, WDR35, ZIC1, ZNF462.
CPT Codes
81404 (x3), 81405, 81479
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
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.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
The craniosynostosis (CSS) syndromes are a genetically heterogeneous group of disorders characterized by premature fusion of sutures of the skull. The clinical features of CSS often overlap and vary in terms of complexity and severity. Clinical features that may be observed in association with craniosynostosis include developmental delay, seizures, hand and foot anomalies, and characteristic facial features [GeneReviews 2020, PMID: 20301628].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for the Craniosynostosis panel is not yet well established and can depend on the patient's clinical features. The genes that are expected to have the highest yield of disease-causing variants are FGFR2, FGFR3, TWIST1, and EFNB1. Copy number variants have been reported in most of the genes on this panel, although they are typically significantly less common than pathogenic sequence variants in these genes.
Utility
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. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Craniosynostosis panel V2 includes genes known to be associated with craniosynostosis and related genetic disorders such as Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, Jackson-Weiss syndrome, Muenke syndrome, isolated coronal synostosis, Saethre-Chotzen syndrome, Antley-Bixler syndrome, Baller-Gerold syndrome, Carpenter syndrome, cranioectodermal dysplasia, and Shprintzen-Goldberg syndrome. The following genes are included: ALPL, ASXL1, CD96, CDC45, CYP26B1, EFNB1, ERF, FGFR1, FGFR2, FGFR3, IFT122, IFT43, IL11RA, MASP1, MEGF8, MSX2, POR, RAB23, RECQL4, RUNX2, SKI, SLC25A24, SMAD6, SPECC1L, TCF12, TGFBR1, TGFBR2, TWIST1, WDR35, ZIC1, ZNF462.
