Isolated bilateral zeugo-autopodal segments agenesis of the lower limb: unusual malformation case report.

Christiaens, Antoine [UCL] Deprez, Pierre ML Mendola, Antonella [UCL] Bernard, Pierre [UCL] Clapuyt, Philippe [UCL] Godfraind, Catherine Lengelé, Benoît [UCL] Vikkula, Miikka [UCL] Behets Wydemans, Catherine [UCL] et al.[show all]

Congenital limb abnormalities represent a prevalence of 0.79/1000 of live births in Massachusetts1. A better understanding of their physiopathology could improve the management of the patients. We report on a 23 weeks female fetus affected by an isolated bilateral terminal transverse defect of the lower limbs with nubbins. Both familial history and chromosomal analyses were irrelevant. We performed a deep morphological examination of the fetus in comparison with an age-matched control fetus in order to precise the diagnosis. The estimated skeleton age corresponded to the gestational age. The bones of both legs and feet were completely lacking, whereas no abnormality was observed in the axial and upper limb skeleton as well as in the other systems. The distal femur epiphysis presented an unusual shape and was composed of a cartilage bud including the proximal tibia anlage. Targeted sequencing of exons involved in limb morphogenesis was carried out with skin tissue and showed no significant mutation. Such a rare malformation was never reported in the medical literature. Considering the data available in the literature, we can suggest the genetic cause is the most probable. Only few theories exist to explain the limb and joint development and malformation. This extremely rare malformation comes up against some contradictory theories, like the Progress Zone model2 and the Early Specification model3. The minute description of the present case is a real chance to give cues to the correct understanding of limb and joint formation, especially the chronological sequence of the different genes, molecules and targets involved in limb morphogenesis.