Intrafamilial Phenotypic Heterogeneity in a Chinese Family with a POLR1D p.Q31Rfs*10 Variant: A Challenge in Prenatal Diagnosis.

Introduction: Treacher Collins syndrome (TCS), also known as mandibulofacial dysostosis, is an inherited craniofacial defect. Here, we report a TCS family in which the members carry the same POLR1D variant but present with phenotypic variability. Case Presentation: A 19-year-old healthy primigravida was revealed by ultrasound at 12 weeks of gestation to have a fetus with micrognathia. Prenatal genetic testing detected a heterozygous single-nucleotide deletion (NM_015972:c.91del, p.Q31Rfs*10) in the POLR1D gene, inherited from the healthy mother. Variants of POLR1D have been reported to be associated with TCS. Family studies found that a paternal healthy cousin of the mother had a similar pregnancy outcome, with a fetus of TCS and the same POLR1D variant. Discussion: Our study results pose a great challenge to prenatal diagnosis of TCS. The prenatal diagnosis cannot only rely on genetic testing. Instead, an early detailed sonographic survey will be helpful for the identification of TCS.