Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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
5 ml whole blood or 2 ug extracted DNA
Minimum Required
3 ml whole blood
Phlebotomy Draw
Yes
Clinical Features
The classical phenotype described for Saethre-Chotzen syndrome (SCS) [OMIM#101400] is synostosis of the coronal sutures of the skull resulting in facial dysmorphologies including asymmetry to the face, hypertelorism and maxillary hypoplasia. Frequently, a high forehead with a low hairline, drooping eyelids, conductive deafness, cleft palate, deviated nasal septum and malocclusions are also present. Brachydactyly and cutaneous syndactyly between the second and third fingers and toes are also seen in the majority of cases. Mild to moderate mental retardation is often present. There is significant phenotypic overlap between SCS and Muenke syndrome [OMIM#602849]. Both share the features of unilateral or bilateral coronal synostosis. Individuals with Muenke syndrome do not have the following features of SCS: distinctive facial features, including low-set frontal hairline, downward sloping palpebral fissures; ptosis; ear abnormalities; interdigital webbing. Compared to persons with SCS, individuals with Muenke syndrome may have a higher prevalence of developmental delay and sensorineural hearing loss.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
21 days
Detection Rate
Sequence analysis of the coding regions of TWIST1 identify pathogenic variants in 46-80% of individuals with a clinical diagnosis of SCS [PMIDs: 16251895, 9585583, 15923834]. One study revealed 11% of persons with deletions detected by copy number analysis [PMID: 14513358].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at-risk family members.
Synonyms
Muenke Syndrome, Coronal synostosis
SCSP
LIS Mnemonic
SCSP
Available STAT
No
Test Notes
Sequence and deletion analysis of the coding region of the TWIST gene. Due to the phenotypic overlap between Muenke syndrome and Saethre-Chotzen syndrome, analysis for the p.Pro250Arg mutation in the FGFR3 gene is included in the Saethre-Chotzen panel.
Molecular Testing Notes
TWIST1, located on chromosome 7p21, is the only gene in which heterozygous pathogenic variants are known to cause SCS. Muenke syndrome is caused by the specific point mutation p.Pro250Arg in FGFR3 (encoding fibroblast growth factor receptor 3).
CPT Codes
81403, 81404
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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
5 ml whole blood or 2 ug extracted DNA
Minimum Required
3 ml whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
The classical phenotype described for Saethre-Chotzen syndrome (SCS) [OMIM#101400] is synostosis of the coronal sutures of the skull resulting in facial dysmorphologies including asymmetry to the face, hypertelorism and maxillary hypoplasia. Frequently, a high forehead with a low hairline, drooping eyelids, conductive deafness, cleft palate, deviated nasal septum and malocclusions are also present. Brachydactyly and cutaneous syndactyly between the second and third fingers and toes are also seen in the majority of cases. Mild to moderate mental retardation is often present. There is significant phenotypic overlap between SCS and Muenke syndrome [OMIM#602849]. Both share the features of unilateral or bilateral coronal synostosis. Individuals with Muenke syndrome do not have the following features of SCS: distinctive facial features, including low-set frontal hairline, downward sloping palpebral fissures; ptosis; ear abnormalities; interdigital webbing. Compared to persons with SCS, individuals with Muenke syndrome may have a higher prevalence of developmental delay and sensorineural hearing loss.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
21 days
Detection Rate
Sequence analysis of the coding regions of TWIST1 identify pathogenic variants in 46-80% of individuals with a clinical diagnosis of SCS [PMIDs: 16251895, 9585583, 15923834]. One study revealed 11% of persons with deletions detected by copy number analysis [PMID: 14513358].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at-risk family members.
Synonyms
Muenke Syndrome, Coronal synostosis
SCSP
LIS Mnemonic
SCSP
Available STAT
No
Test Notes
Sequence and deletion analysis of the coding region of the TWIST gene. Due to the phenotypic overlap between Muenke syndrome and Saethre-Chotzen syndrome, analysis for the p.Pro250Arg mutation in the FGFR3 gene is included in the Saethre-Chotzen panel.
Molecular Testing Notes
TWIST1, located on chromosome 7p21, is the only gene in which heterozygous pathogenic variants are known to cause SCS. Muenke syndrome is caused by the specific point mutation p.Pro250Arg in FGFR3 (encoding fibroblast growth factor receptor 3).
