| DNA Diagnostic Laboratory at Johns Hopkins |  |
| DNA Diagnostic Laboratory at Johns Hopkins | |
Saethre-Chotzen Syndrome |
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| Genes: |
FGFR2; chr10q26.13 FGFR3; chr4p16.3 TWIST1; chr7p21.1 |
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| Syndrome Information | ||
| Clinical Description: |
Saethre-Chotzen Syndrome is associated most commonly with unilateral or
bilateral coronal synostosis (though any suture may be involved).
Patients may have facial asymmetry, low frontal hairline, ptosis,
strabismus, and soft-tissue syndactyly of fingers or toes. The ears
have a characteristic shape with small pinna and prominent crus.
Conductive, mixed, or sensorineural hearing loss may be present.
Also variably reported are short stature, congenital heart defects,
vertebral fusions, and hypertelorism. Intelligence is generally
normal (see Genotype-Phenotype section for additional information). |
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| Inheritance Pattern: | Autosomal Dominant; Variable expressivity and incomplete penetrance have been reported. | |
| Genotype-Phenotype Correlation: | None, generally. Patients with TWIST1 gene deletions have a higher incidence of developmental delay. Point mutations in the c-terminal TWIST box may cause a milder phenotype of isolated craniosynostosis (saggital or unilateral coronal) |
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| Test Information | ||
| Test Method: | Bidirectional
sequencing of selected exons and intron-exon boundaries FGFR2 exon 7**; FGFR3 exon 7; TWIST1 complete coding region (** This exon is also called "8"depending on the transcript used for analysis.)
Automatically reflexed to TWIST1
multiplex ligation-dependent probe amplification (MLPA) for deletions |
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| Clinical Utility: | Identification
of causative mutations in known or highly suspicious cases of
Saethre-Chotzen Syndrome; Assessment of recurrence risk within the family;
targeted diagnostic testing of relatives of proband with inconclusive
clinical presentations; predictive
prenatal testing when familial mutation is known. |
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| Clinical Sensitivity: |
Sequence: Approximately 68% of patients with
Saethre-Chotzen
syndrome will have a mutation detectable by this sequencing panel.
MLPA:
Approximately 7% of
patients with Saethre-Chotzen Syndrome are predicted to have a large
TWIST1 deletion detectable by a dose-sensitive test such as MLPA |
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Analytic Sensitivity: |
Sequence panel: Greater
than 97% for nucleotides analyzed. All reports will indicate if
a certain percentage of nucleotides were not called or were analyzed
in a single direction.
MLPA:
Estimated to be at least
90%. |
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| Sample Requirements: |
For tests utilizing MLPA, we are only able
to accept whole blood drawn in EDTA (purple or lavender top) tubes and
Qiagen Puregene extracted DNA. |
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| Turn Around Time: |
Sequencing: 3 weeks MLPA: 4 weeks |
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| Fee and CPT Codes: |
Sequence:
$662 for routine
testing on a blood sample 83891 x 1; 83898 x 4; 83904 x 8; 83909 x 8; 83912 x 1 TWIST1 MLPA:
$429 for routine testing on a blood sample Please contact the lab to arrange testing for known mutations on blood or prenatal samples. |
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| Special Considerations | ||
| Clinical findings in Saethre-Chotzen Syndrome may overlap with those of other FGFR-related craniosynostosis syndromes. | ||
| INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download. | ||
Helpful Links |
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| Sample Requirements Requisition and Billing forms Clinical information on Saethre-Chotzen Syndrome Link to the General Test Information page for a discussion of the uses and limitations of genetic testing Patient and Family Page for general resources on genetic testing. |
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