Table 2 Summary of clinical and genetic features for each of the five fetuses where a conclusive molecular diagnosis could not be achieved.
From: Genome sequencing in a cohort of 32 fetuses with genetic skeletal disorders
Nr | Clinical diagnosis | Sex | GA | Tissue | Clinical features | Molecular findings |
|---|---|---|---|---|---|---|
28 | Orofaciodigital syndrome | M | 16+ | AF, blood | Born at 37 weeks to healthy non-consanguineous parents. Antenatal detection of skeletal and intracranial abnormalities and polyhydramnios. Microcephaly, microretrognathia, tongue hamartoma. Small hands with broad big toes and thumbs. Postaxial polydactyly/soft tissue of the hands. Preaxial polydactyly of the feet. | CEP290: NM_025114.4 c.(164_167delCTCA), p.(Thr555Serfs*3) inherited from father CEP120: NM_153223.4 c.(2917C>T), p.(Arg947*) inherited from mother. Two intronic variants inherited from father: c.(−33+214C>T) and c.(2580+5133T>A) |
29 | Osteogenesis imperfecta | M | 18+ | CVB | Terminated at week 19. Healthy non-consanguineous parents, first pregnancy. Ultrasound at GA 18 + 2 showed a suspected left femur fracture and short long bones. Autopsy confirmed an older femur fracture and thinner diaphysis, no dysmorphic features, and no inner organ anomalies. No reports on decreased fetal movements during pregnancy. | No variant detected |
30 | Metaphyseal osteosclerosis | M | 17+ | Fetal tissue | Missed abortion at week 17. Healthy non-consanguineous parents, four previous early miscarriages. | No variant detected |
31 | Spondylocostal dysostosis | M | 20 + 1 | Fetal tissue | Terminated at 20 weeks. Healthy non-consanguineous parents. Multiple segmentation anomalies, scoliosis, left hip dislocation, and overlapping fingers on the left hand. No dysmorphic features. Abnormal external genitalia, anal atresia, absent left kidney and ureter, with right kidney showing mild hydronephrosis and abnormal ureter. | No variant detected |
32 | Ectrodactyly, peromelia | M | 20+ | Fetal tissue | Terminated at 20+ weeks. Bilateral absence of feet and left hand with shortened fingers 2–4 and partial syndactyly between digits 4 and 5. Right hand with shortened fingers 1 and 5, and stumps of fingers 2–4. Mild bilateral hydroureter. | No variant detected |
