A fetal case of Stüve-Wiedemann syndrome due to a novel homozygous truncating variant in IL6ST

Stüve-Wiedemann syndrome is a rare skeletal dysplasia characterized by severe shortening and bowing of the long bones and by immunological and autonomous dysfunction, usually resulting in early death. Bi-allelic loss-of-function variants in either the leukemia inhibitory factor receptor encoding LIFR or the interleukin-6 cytokine family signal transducer encoding IL6ST are causative. So far, five individuals from three unrelated families were described with IL6ST associated Stüve-Wiedemann syndrome. We here report on a sixth case that came to attention at 21 weeks of gestation with short and bowed long bones. Prenatal trio exome sequencing revealed the homozygous novel variant p.(Ser375∗) in IL6ST in the fetus. The further course of the pregnancy was complicated by early rupture of the membranes and preeclampsia. The fetus died in utero in gestational week 34 and was born with dolichocephalus, severe bowing and shortening of limb bones, a narrow upper thorax, joint dislocations and abnormal bone mineralization. With this case report, we further delineate the molecular and clinical spectrum of IL6ST related Stüve-Wiedemann syndrome.