Treacher Collins Syndrome

Locus (OMIM)Gene (OMIM)InheritanceKey Locus References (PubMed)Key Gene References (PubMed)
Evidence (ClinGen)
TCS1TCOF1Autosomal DominantBalestrazzi et al., 1983; Jabs et al., 1991; Dixon et al., 1992; Dixon et al., 1993Treacher Collins Syndrome Collaborative Group, 1996Definitive
TCS2POLR1DAutosomal DominantDauwerse et al., 2011Dauwerse et al., 2011not reviewed
TCS3POLR1CAutosomal RecessiveDauwerse et al., 2011Dauwerse et al., 2011Moderate
TCS4POLR1BAutosomal DominantSanchez et al., 2020Sanchez et al., 2020not reviewed


Treacher Collins syndrome is characterized by coloboma of the lower eyelid (the upper eyelid is involved in Goldenhar syndrome), micrognathia, microtia, hypoplasia of the zygomatic arches, macrostomia, and inferior displacement of the lateral canthi with respect to the medial canthi. The disease-causing gene, TCOF1, encodes a protein of 1,411 amino acids (TREACLE) with a structure that is shared with nucleolar trafficking proteins in other species, suggesting that TCOF1 plays a role in nucleolar-cytoplasmic transport. The detection rate for mutations in this gene in persons with the TCOF1 phenotype is approximately 60%, and in nearly all cases, the result is the introduction of a premature stop codon into the predicted protein (Edwards et al., 1997).