Molecular analysis of 31 cases with fetal skeletal dysplasia

The aim of this study was to describe the prenatal ultrasound findings of fetuses with skeletal dysplasia and to evaluate the genetic variations by molecular genetic analysis.

Between August 1, 2018 and March 1, 2023, we conducted a retrospective case series at a tertiary referral center involving patients with fetal skeletal abnormalities. For cases referred for a possible diagnosis of fetal skeletal dysplasia, an ultrasound database and prenatal genetic counseling records were first searched. Terminated cases diagnosed with skeletal dysplasia by pathologic and radiologic findings and cases with skeletal dysplasia proven by postnatal clinical findings were included in the study.

Between 2018 and 2023, a total of 64 cases were diagnosed as skeletal dysplasia based on radiologic findings, pathologic findings, and clinical features. The median week of the first ultrasound performed on patients is 19 0/7 weeks, while the median week of the ultrasound in which skeletal dysplasia is suspected is 21 3/7 weeks. Although micromelia was evaluated as a common feature in all cases, the most common concomitant anomaly was thoracic hypoplasia. Exome sequencing analysis was achieved in 31 (48 %) of cases. In 31 cases, in total of 35 pathogenic single gene mutations and 5 VUS (variants of uncertain significance) variants composing of 23 autosomal dominant, 10 autosomal recessive and 2 X linked recessive mutations were determined.

Prenatal ultrasound findings can lead us to specific diagnoses, and with the appropriate molecular analysis method, a definitive diagnosis can be made without wasting time and money.