Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Genet Med. 2016 Jan;18(1):49-56. doi: 10.1038/gim.2015.29. Epub 2015 Mar 19.


Purpose: Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C.

Methods: We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene.

Results: We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature.

Conclusion: Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • DNA-Directed RNA Polymerases / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Mandibulofacial Dysostosis / diagnosis
  • Mandibulofacial Dysostosis / genetics*
  • Microcephaly / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Peptide Elongation Factors / genetics
  • Phosphoproteins / genetics*
  • Ribonucleoprotein, U5 Small Nuclear / genetics
  • Sequence Deletion
  • Young Adult


  • EFTUD2 protein, human
  • Nuclear Proteins
  • Peptide Elongation Factors
  • Phosphoproteins
  • Ribonucleoprotein, U5 Small Nuclear
  • TCOF1 protein, human
  • DNA-Directed RNA Polymerases
  • POLR1C protein, human
  • POLR1D protein, human