Distributed X chromosome inactivation in brain circuitry is associated with X-linked disease penetrance of behavior.

The precise anatomical degree of brain X chromosome inactivation (XCI) that is sufficient to alter X-linked disorders in females is unclear. Here, we quantify whole-brain XCI at single-cell resolution to discover a prevalent activation ratio of maternal to paternal X at 60:40 across all divisions of the adult brain. This modest, non-random XCI influences X-linked disease penetrance: maternal transmission of the fragile X mental retardation 1 (Fmr1)-knockout (KO) allele confers 55% of total brain cells with mutant X-active, which is sufficient for behavioral penetrance, while 40% produced from paternal transmission is tolerated. Local XCI mosaicism within affected maternal Fmr1-KO mice further specifies sensorimotor versus social anxiety phenotypes depending on which distinct brain circuitry is most affected, with only a 50%-55% mutant X-active threshold determining penetrance. Thus, our results define a model of X-linked disease penetrance in females whereby distributed XCI among single cells populating brain circuitries can regulate the behavioral penetrance of an X-linked mutation.

Feeding Difficulties Following Vascular Ring Repair: A Contemporary Narrative Review.

Vascular rings are congenital abnormalities of the aortic arch vascular system that compress the trachea and esophagus. A review of long-term outcomes suggests that chronic feeding difficulties can persist following surgical repair of vascular rings. Previous reports of postoperative vascular ring division outcomes indicate that chronic esophageal symptoms may persist following repair, though most available data focuses on persistent respiratory symptoms. It is therefore the aim of this article to summarize and organize recent evidence reporting the frequency, presentation, and management of feeding difficulties following vascular ring repair in pediatric patients. Pathophysiologic mechanisms for postoperative esophageal symptoms may include residual compression from an unresected diverticulum of Kommerell or delayed repair leading to chronic esophageal dysmotility despite correction of esophageal compression. Guidance on the management of feeding difficulties following vascular ring repair is limited. The authors describe success in one case with nasogastric tube feeding and interdisciplinary evaluation. Consensus regarding the management of feeding difficulty following vascular ring repair is needed.