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Treacher Collins Syndrome
Genes: TCOF1; chr5q32  (TCS1) POLR1D; chr13q12.2  (TCS2) POLR1C; chr6p21.1  (TCS3)
Syndrome Information
Clinical Description:    Treacher Collins Syndrome (TCS) primarily affects craniofacial development.  The most common features include downward slanting palpebral fissures and lower lid coloboma; hypoplasia of malar bones and micrognathia; dysmorphic or hypoplastic external ears; and atresia of middle-ear ossicles sometimes resulting in conductive hearing loss.  Cleft palate and unilateral or bilateral choanal atresia are also possible.  
Inheritance Pattern:  Autosomal Dominant (TCOF1, POLR1D); Autosomal Recessive (POLR1C);
ariable expressivity and non-penetrance have been reported
Genotype-Phenotype Correlation: None known; reported TCS caused by POLR1D and POLR1C mutations is clinically indistinguishable from that caused by TCOF1 mutations
Test Information
Test Method:  Next Generation Sequencing (NGS) and/or Sanger sequencing of the coding regions and intron-exon boundaries of the listed genes; Automatically reflexed to TCOF1 deletion/duplication testing by MLPA analysis if needed.     
Clinical Utility: Identification of causative mutations in known or highly suspicious cases of Treacher Collins 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.  
Clinical Sensitivity: Between 78 and 93% of patients with a clinical diagnosis of Treacher Collins Syndrome are expected to have a point mutation in TCOF1, depending on diagnostic stringency.  Of TCOF1 negative patients, approximately 7% are expected to have POLR1D mutations and 1% are expected to have POLR1C mutations

TCOF1 del/dup: Approximately 2-4% of patients with Treacher Collins Syndrome will have a TCOF1 deletion.  Deletions comprise approximately 5% of TCOF1 mutations.   

Analytic Sensitivity:   

Sequencing:  >99% accuracy for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated.   Sequence analysis parameters are not designed to assess mosaicism.  

Del/Dup:  Greater than 99% for MLPA probes analyzed.
Turn Around Time:   Sequence:  Approximately 4 weeks

TCOF1 MLPA: up to 4 weeks
Fee and CPT Codes:    Sequence:  $2601 for routine testing
81479 x3

TCOF1 MLPA:  $429 for routine testing

Please contact the lab to arrange testing for known mutations on blood or prenatal samples. 

Special Considerations
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
Sample Requirements
Requisition and Billing forms
Clinical information on Treacher Collins Syndrome
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.