A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity

Clin Genet. 2023 Feb;103(2):146-155. doi: 10.1111/cge.14243. Epub 2022 Oct 17.


Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

Keywords: POLR1B; POLR1C; POLR1D; TCOF1; Treacher Collins syndrome; clinical severity; genotype-phenotype correlations.

Publication types

  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Directed RNA Polymerases / genetics
  • Genetic Association Studies*
  • Humans
  • Mandibulofacial Dysostosis* / diagnosis
  • Mandibulofacial Dysostosis* / genetics
  • Mutation / genetics


  • DNA-Directed RNA Polymerases
  • POLR1D protein, human