Prenatal diagnosis of genetic aberrations in fetuses with short femur detected by ultrasound: A prospective cohort study.

Abstract

To investigate the genetic aberrations in fetuses with short femur and explore the relationships with respect to degree of femoral shortening and the initial diagnostic gestational age GA. Singleton pregnancies with fetal short femur who consented to amniocentesis and to single nucleotide polymorphism (SNP) array and Sanger sequencing for G380R mutations in FGFR3 gene were enrolled in this 5-year period prospective study. Clinical follow-up assessments were performed after birth. Of a total of 161 fetuses, the prevalence of genetic aberrations was 16.2% (26/161), comprised of 65.4% (17/26) with chromosomal abnormalities and 34.6% (9/26) with G380R mutations. All fetuses with chromosomal abnormalities had FL 2-4SDs below GA. Fewer chromosomal abnormalities were detected in fetuses with short femurs presenting in the third trimester. Significantly more FGFR3 mutations were detected in fetuses with FL below -4SDs. All fetuses with FL 2-4SDs below GA diagnosed as achondroplasia were between 22 and 24 gestational weeks, and all of those diagnosed in third trimester had FL below -4SDs. In this small cohort study, we demonstrated that different degrees of femur shortness may be attributed to different genetic aberrations. SNP array should be regarded as the first-tier test for fetuses with FL 2-4SDs below GA. The prognoses for fetuses with FL 2-4SDs below GA was significantly better than those with FL below 4SDs.