Congenital intestinal malrotation presenting in octogenarians: a report of two cases

Malrotation is part of a spectrum of small and large bowel positional and fixational abnormalities caused by the failure of the fetal intestine to complete a 270-degree rotation around the superior mesenteric artery axis. Rarely, it presents in the adult as a cause of acute small bowel obstruction. Chronic symptoms of malrotation in adults are subtle, and include intermittent abdominal pain, nausea and vomiting. We present two cases of malrotation in octogenarian men presenting acutely with small bowel obstruction. Both patients were treated with emergency surgery. In one case the chronic symptoms resolved postoperatively. Malrotation and midgut volvulus should be considered as a rare differential diagnosis for small bowel obstruction in adults. Suspicions should be increased when there is a history of recurrent presentations with similar symptoms.

HNF4 factors control chromatin accessibility and are redundantly required for maturation of the fetal intestine

ABSTRACTAs an embryo matures into a fetus, cells undergo remarkable transitions, accompanied by shifts in transcription factor regulatory networks and chromatin landscapes. The mechanisms of these developmental transitions are not completely understood. The embryonic intestine transitions from a rapidly proliferating tube with pseudostratified epithelium prior to embryonic day (E) 14.5, to an exquisitely folded columnar epithelium in the fetus. We sought to define factors that drive fetal maturation of the intestine. ATAC-seq profiling revealed a dramatic restructuring of intestinal chromatin during the embryonic-to-fetal transition, with CDX2 transcription factor motifs abundant at chromatin-accessible regions of the embryo, and hepatocyte nuclear factor 4 (HNF4) transcription factor motifs the most abundant in the fetal stages. Genetic inactivation of Hnf4α and its paralog, Hnf4γ, revealed that HNF4 factors are redundantly and vitally required for fetal maturation. In the embryo, CDX2 binds to and activates Hnf4 gene loci to drive HNF4 expression at fetal stages. HNF4 and CDX2 transcription factors then occupy shared genomic regulatory sites and are required for chromatin accessibility at genes expressed in the maturing fetal intestine. Thus, intestinal transcription factor regulatory networks shift to accompany changing chromatin landscapes and gene expression profiles that occur during the transition of an embryonic tissue to its mature state.