A Truncating Variant of CHRNG as a Cause of Escobar Syndrome: A Multiple Pterygium Syndrome Subtype.

Escobar syndrome is a milder variant of multiple pterygium syndrome characterized by pterygia, scoliosis, and multiple congenital contractures. It is most frequently due to a genetic variant in CHRNG , which encodes the γ-subunit of the nicotinic acetylcholine receptor. Though the subunit is considered a "fetal" form and transitions to the "adult" ε-subunit by 33 weeks' gestation, the pathogenic musculoskeletal effects during fetal development render children with this condition permanently affected. We report a neonate with homozygous CHRNG c.117dupC and discuss some of the downstream clinical effects we observed with this variant.

Validity of Random Triglyceride Levels in Infants Receiving Parenteral Nutrition.

Background: Intravenous lipid emulsions (IL) are an important part of parenteral nutrition (PN) to meet essential fatty acid (EFA) requirements and metabolic demands of neonates and preterm infants. Some critically-ill neonates may not metabolize IL effectively which can lead to hypertriglyceridemia. Risks associated with this include increased pulmonary vascular resistance, displaced bilirubins, and platelet or macrophage dysfunction. Serum triglyceride (TG) concentration is used as a marker for lipid tolerance and predictor of potential complications involved with IL administration, but the clinical significance of this is still debated. Management of TG levels with regard to timing of laboratory tests, the ideal goal range, and duration of infusion of IL varies across institutions and is not standardized. Methods: Single-center, retrospective study of newborn infants receiving parenteral nutrition (PN). Fasting and non-fasting TG levels were drawn during the same lipid infusion of 2-3g/kg/day. The primary outcome was the difference between fasting and non-fasting TG levels. Statistical assessment of continuous data was done with student t-test and nominal data was evaluated using X2-test and logistic regression. Results: Forty infants were included with mean gestational age at birth of 29.5 ± 3.4 weeks and mean birth weight of 1.3 ± 0.5 kg. Mean time between lab draws while on same IL dose was 11.6 ± 0.2 h with resulting mean fasting and non-fasting (random) TG levels 82 ± 40 mg/dL (95% CI 68.4, 97.6) and 101 ± 40 mg/dL (95% CI 88.5, 115.8), respectively. Mean difference between TG levels during lipid-free interval and during infusion was -18.6 ± 51.2 mg/dL (95% CI -35.0, -2.3; p = 0.03). Conclusion: We concluded there is no difference in the management of IL, when TG level was drawn randomly or as fasting sample. Obtaining TG level during routine lab draws is appropriate. We extrapolated that the administration of IL over 24 h will not interfere with TG level.

A Retrospective Review Following the Addition of Clonidine to a Neonatal Abstinence Syndrome Treatment Algorithm.

Objective: To investigate the outcomes associated with the implementation of a neonatal abstinence syndrome (NAS) treatment algorithm utilizing dual therapy with morphine sulfate and clonidine in a level four neonatal intensive care unit (NICU). Study Design: A cohort of neonates (≥35 weeks gestation) born at an academic tertiary medical center between January 1, 2015 and December 31, 2018 who were diagnosed with NAS were retrospectively evaluated following the implementation of a new NAS treatment algorithm. Neonates were categorized in two groups based on if they were treated pre- or post-implementation of the protocol. The primary efficacy outcome was length of hospital stay. Secondary outcomes included the incidence of adverse drug reactions, length of treatment for NAS, and maximum as well as total cumulative dose of each medication used to treat NAS. Results: The implementation of this NAS treatment algorithm significantly reduced the length of hospital stay (30 days vs. 20 days, p = 0.001). In addition, there was a significant decrease in duration of morphine sulfate exposure as well as cumulative dose of morphine required to successfully treat a neonate with NAS in the post-implementation group (26 days vs. 15 days, p = 0.002 and 6.9 mg/kg vs. 3.4 mg/kg, p = 0.031). Conclusion: Addition of clonidine to morphine sulfate as initial therapy for NAS significantly reduced the cumulative exposure as well as duration of exposure to morphine sulfate compared to morphine monotherapy and decrease length of hospital stay.

Genetic Characterization of a Model Ciliopathy: Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a rare ciliopathy affecting multiple organ systems. Patients with BBS are usually diagnosed later in childhood when clinical features of the disease become apparent. In this article, we presented a case of BBS discovered by whole genome sequencing in a newborn with heterotaxy, duodenal atresia, and complex congenital heart disease. Early diagnosis is important not only for prognostication but also to explore ways to mitigate the cone-rod dysfunction and for exploring newer therapies. Our case highlights the importance of a high index of suspicion and the utility of advanced genetic testing to provide an early diagnosis for a rare disease.

Prophylactic inhibition of NF-κB expression in microglia leads to attenuation of hypoxic ischemic injury of the immature brain.

BACKGROUND: Periventricular leukomalacia (PVL), a devastating brain injury affecting premature infants, is the most common cause of cerebral palsy. PVL is caused by hypoxia ischemia (HI) and is characterized by white matter necrotic lesions, microglial activation, upregulation of NF-κB, and neuronal death. The microglia is the main cell involved in PVL pathogenesis. The goal of this study was to investigate the role of microglial NF-κB activity and its prophylactic inhibition in a neonate mouse model of HI. METHODS: Transgenic mice with specific knockout NF-κB in microglia and colony stimulating factor 1 receptor Cre with floxed IKKß (CSF-1R Cre + IKKßflox/wt ) were used. Postnatal day 5 (P5) mice underwent sham or bilateral temporary carotid artery ligation followed by hypoxia. After HI insult, inflammatory cytokines, volumetric MRI, histopathology, and immunohistochemistry for oligodendroglia and microglial activation markers were analyzed. Long-term neurobehavioral assessment, including grip strength, rotarod, and open field testing, was performed at P60. RESULTS: We demonstrate that selective inhibition of NF-κB in microglia decreases HI-induced brain injury by decreasing microglial activation, proinflammatory cytokines, and nitrative stress. Rescue of oligodendroglia is evidenced by immunohistochemistry, decreased ventriculomegaly on MRI, and histopathology. This selective inhibition leads to attenuation of paresis, incoordination, and improved grip strength, gait, and locomotion. CONCLUSION: We conclude that NF-κb activation in microglia plays a major role in the pathogenesis of hypoxic ischemic injury of the immature brain, and its prophylactic inhibition offers significant neuroprotection. Using a specific inhibitor of microglial NF-κB may offer a new prophylactic or therapeutic alternative in preterm infants affected by HI and possibly other neurological diseases in which microglial activation plays a role.

Unique Case of Congenital Duodenal Atresia and a Choledochal Cyst and the Hypothesis of Their Embryological Evolution.

The concomitant occurrence of duodenal atresia (DA) and a choledochal cyst (CC) has rarely been reported. Knowledge of both the presentation and management of this rare co-occurrence is imperative in avoiding potential complications and sequelae, such as biliary metaplasia. Herein we describe a female infant born at 32 weeks gestational age who was diagnosed with duodenal atresia and annular pancreas postnatally, who had subsequent findings of malrotation and a choledochal cyst, as seen from contrast imaging. Uncomplicated repair of the DA and obstruction was performed at 4 days of life. She re-presented 2 years later with non-bloody, nonbilious emesis and was found to have elevated amylase, lipase and liver enzymes. Imaging revealed dilated intra-hepatic ducts, a distended gallbladder and a large choledochal cyst. She underwent a cholecystostomy tube placement followed by a definitive choledochal cyst excision with immediate improvement following surgery and full resolution of symptoms before discharge.