Early prenatal detection of autosomal dominant skeletal dysplasia using first-trimester ultrasound and cell-free fetal DNA screening: three case reports

Case presentations Case 1 (Family 1)A primigravida attended our fetal medicine clinic (FMC) in March 2015 at 12 weeks' gestation for firsttrimester (T1) Down syndrome screening.Ultrasound examination revealed an absent nasal bone (NB).A morphology scan at 20 weeks confirmed this finding, along with bilateral non-ossified parietal bones, 11 pairs of ribs, and shortened femur and humerus.Amniocentesis revealed a normal chromosomal microarray.The couple opted for termination of pregnancy at 22 weeks.A computed tomography babygram confirmed the ultrasound findings and also showed bilaterally absent clavicles, hinting at a diagnosis of cleidocranial dysplasia (CCD).Targeted sequencing of the RUNX2 gene on the amniotic fluid sample revealed a de novo heterozygous pathogenic missense variant, c.674G>A (p.Arg225Gln), confirming the diagnosis.Multimodal prenatal and genetic findings were illustrated in Figure 1.