EP06.09: Expanding prenatal ultrasonographic features in fetal akinesia deformation sequence 3 confirmed by post‐mortem examination

The Fetal Akinesia Deformation Sequence (FADS) is a clinically and genetically heterogeneous disorder. The literature reports only two families with lethal forms of FADS 3 (OMIM*610285) due to pathogenic variants in DOK7 interfering with neurotransmission at the neuromuscular junction. Here, we describe intrauterine evolution and expand the fetal phenotypes of a new family. A non-consanguineous European couple with a history of neonatal death in his first child due to severe bilateral lung hypoplasia was referred for lung hypoplasia and camptodactyly at 24 weeks of gestation (WG). Six months later, another pregnancy in this couple was affected by progressive pulmonary hypoplasia, which established at 18 WG and the appearance of camptodactyly and Talipes equinovarus (see figure 1). After prenatal counselling and parental request, terminations of pregnancy were performed at 26 and 27 WG according to French law. Postmortem examination confirmed all prenatal findings and identified facial dysmorphism with retrognathia. The whole genome sequencing identified a heterozygous composite of two variants affecting DOK7: c.437G>A (p.(Arg158Gln) situated at exon 4 and variant c.773-2_773-1del at the level of intron 6, classified as pathogenic and likely pathogenic according to the ACMG-AMP guidelines. Here, we demonstrate that reduced observed/expected lung-to-head ratio and elevation of diaphragmatic domes are ultrasound markers of lung hypoplasia in FADS. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.