Fetal akinesia: The application of clinical exome sequencing in cases with decreased fetal movement

Objective: To determine monogenic syndromes in cases of fetal akinesia in order to understand the genetic aetiology.

Study design: Clinical trio exome sequencing (ES) was performed on DNA extracted from postnatal samples in 12 cases with fetal akinesia identified by prenatal ultrasound and a normal chromosomal micro-array analysis result. This test targets coding exons for 4200 clinically relevant disease-causing genes. The interpretation of variants was performed according to the guidelines of the American College of Medical Genetics.

Results: A definite molecular diagnosis was achieved in six (50 %) of the 12 cases using clinical trio ES. In five cases, the pathogenic variants were located in known fetal-akinesia-associated genes. In one case, the underlying pathogenic variants were in known disease genes that had not been linked to fetal akinesia previously. Six pregnancies were terminated by the parents, and six pregnancies were continued to term.

Conclusion: Genetic defects leading to fetal akinesia were found in half of the study cases using clinical trio ES. This information will be useful in genetic counselling with regard to prognosis and risk of recurrence.