Variants in TCOF1 cause Treacher Collins syndrome also named (Treacher Collins-) Franceschetti syndrome and belongs to the group of mandibulofacial dysostosis.
Main clinical features
The distinctive facial features in Treacher Collins syndrome (TCS) include:
• Downward-slanting palpebral fissures
• Midface hypoplasia: hypoplasia/aplasia of the zygomatic arch and malar hypoplasia
• Micrognathia, retrognathia and mandibular hypoplasia
• External ear abnormalities
• Lower eyelid abnormalities
The classic facial features of Treacher Collins syndrome are bilateral and symmetric. Inter- and intrafamilial phenotypic variability is high, some individuals are so mildly affected that they remain undiagnosed.
The majority of patients have conductive hearing loss due to external and middle ear defects.
A smaller subset of patients has coloboma of the lower eyelid, cleft palate and/or choanal stenosis/atresia.
Typically, the intellect and fertility is normal.
Prevalence
The prevalence of Treacher Collins syndrome is estimated to be 1/50 000.
About 70-85% TCS cases with typical facial features carry a variant in the TCOF1 gene.
Inheritance
TCS due to mutations in the TCOF1 gene is inherited in an autosomal dominant manner. There are no genotype/phenotype correlations known.
Manifestations
The craniofacial anomalies can lead to clinical manifestations including airways, ophthalmic and dental issues and sleep apneas. Treatment is symptomatic and multidisciplinary.
TCOF1