Jarcho-Levin syndrome term baby with recurrent apnea

Jarcho-Levin syndrome or spondylocostal dysostosis, is a rare axial skeleton anomaly due to mutation in genes involved in somitic segmentation during embryogenesis. We describe a term, newborn baby with antenatally detected midthoracic lordotic deformity with skeletal features of multiple rib anomalies and vertebral defects, but with normal limb lengths. Baby had recurrent apnea requiring non-invasive ventilation and was successfully weaned to room air within 2 days. This syndrome is underdiagnosed and we wish to highlight the simple process involved in making a clinico-radiological diagnosis.

CASE OF VACTERLASSOCIATION WITHOUT THE "V AND L": ANAESTHETIC CHALLENGES

Aim & Objective: To highlight the importance of anesthetic management in a small neonate with cleft lip, cleft palate, single kidney, atrial septal defect, posted for trachea-oesophageal stula repair. Case description:Afemale baby born at 35 weeks of gestation to a 23-year-old primigravida mother by caesarean section in view of foetal distress with breech presentation .Baby had difculty in breathing and froathing from mouth. Cleft lip and cleft palate was present. Anasogastric tube was not going beyond 11 cm per oral route. Chest x ray showed coiling of tube in upper esophagus.F/S/O Type C Tracheo esophageal stula. . Plain Xray abdomen showed presence of bowel gas. Ultrasonography of the abdomen showed right renal agenesis. The left kidney was normal. Echocardiography showed presence of atrial septal defect with left to right shunt, tiny patent ductusarteriosus, mild pulmonary arterial hypertension, mild tricuspid regurgitation. Based on the presence of tracheoesophagealstula, atrialseptal defect, unilateral renal agenesis and absence of features, suggestive of alternative diagnosis infant, meet criteria of vacteral association. Discussion: VACTERL is a cluster of congenital malformations based on the non-random association of various congenital malformations in a single patient. Here “V” denotes vertebral defects or vascular anomalies (single umbilical artery), “A” anal atresia, “C” cardiac abnormalities, “TE” tracheoesophageal stula, “R"renal (kidney) abnormalities and “L” for limb anomalies) Diagnosis of VACTERL association is done only when at least three of the above mentioned congenital malformations are identied in a patient. Although 80% of these cases have vertebral defects, our case is unique as patient does not have one of the commonest occuring association i.e., vertebral anomalies. The other highlight of this case is although reports say that VACTERL babies with ipsilateral renal disorder have the same side limb defects, our case has a renal anomaly with no limb anomaly. Conclusion: Anaesthetic challenges were difcult airway, endotracheal tube placement, low respiratory reserve, small maximum allowable blood loss, long duration of surgery, risk of hypothermia, aspiratedlungs, risk of right to left shunt, difculty in securing intravenous line and intra arterialline. this case needs continuous monitoring of ECG, invasive blood.

Neonatal Respiratory Distress and Airway Emergency: Report of Two Cases

We discuss two cases of congenital airway malformations seen in our neonatal intensive care unit (NICU). The aim is to report extremely rare events characterized by immediate respiratory distress after delivery and the impossibility to ventilate and intubate the airway. The first case is a male twin born at 34 weeks by emergency caesarean section. Immediately after delivery, the newborn was cyanotic and showed severe respiratory distress. Bag-valve-mask ventilation did not relieve the respiratory distress but allowed for temporary oxygenation during subsequent unsuccessful oral-tracheal intubation (OTI) attempts. Flexible laryngoscopy revealed complete subglottic obstruction. Postmortem analysis revealed a poly-malformative syndrome, unilateral multicystic renal dysplasia with a complete subglottic diaphragm, and a tracheo-esophageal fistula (TEF). The second case is a male patient that was vaginally born at 35 weeks. Antenatally, an ultrasound (US) arose suspicion for a VACTERL association (vertebral defects, anal atresia, TEF with esophageal atresia and radial or renal dysplasia, plus cardiovascular and limb defects) and a TEF, and thus, fetal magnetic resonance (MRI) was scheduled. Spontaneous labor started shortly thereafter, before imaging could be performed. Respiratory distress, cyanosis, and absence of an audible cry was observed immediately at delivery. Attempts at OTI were unsuccessful, whereas bag-valve-mask ventilation and esophageal intubation allowed for sufficient oxygenation. An emergency tracheostomy was attempted, although no trachea could be found on cervical exploration. Postmortem analysis revealed tracheal agenesis (TA), renal dysplasia, anal atresia, and a single umbilical artery. Clinicians need to be aware of congenital airway malformations and subsequent difficulties upon endotracheal intubation and must plan for multidisciplinary management of the airway at delivery, including emergency esophageal intubation and tracheostomy.

Fgf4 maintains Hes7 levels critical for normal somite segmentation clock function

During vertebrate development, the presomitic mesoderm (PSM) periodically segments into somites, which will form the segmented vertebral column and associated muscle, connective tissue, and dermis. The periodicity of somitogenesis is regulated by a segmentation clock of oscillating Notch activity. Here, we examined mouse mutants lacking only Fgf4 or Fgf8, which we previously demonstrated act redundantly to prevent PSM differentiation. Fgf8 is not required for somitogenesis, but Fgf4 mutants display a range of vertebral defects. We analyzed Fgf4 mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 maintains Hes7 levels and normal oscillatory patterns. To support our hypothesis that FGF4 regulates somitogenesis through Hes7, we demonstrate genetic synergy between Hes7 and Fgf4, but not with Fgf8. Our data indicate that Fgf4 is potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.

OPF/PMMA Cage System as an Alternative Approach for the Treatment of Vertebral Corpectomy

The spinal column is the most common site for bone metastasis. Vertebral metastases with instability have historically been treated with corpectomy of the affected vertebral body and adjacent intervertebral discs, and have more recently been treated with separation surgery. With demographics shifting towards an elderly population, a less-invasive surgical approach is necessary for the repair of vertebral defects. We modified a previously reported expandable hollow cage composed of an oligo[poly(ethylene glycol) fumarate] (OPF) containment system that could be delivered via a posterior-only approach. Then, the polymer of interest, poly (methyl methacrylate) (PMMA) bone cement, was injected into the lumen of the cage after expansion to form an OPF/PMMA cage. We compared six different cage formulations to account for vertebral body and defect size, and performed a cage characterization via expansion kinetics and mechanical testing evaluations. Additionally, we investigated the feasibility of the OPF/PMMA cage in providing spine stability via kinematic analyses. The in-vitro placement of the implant using our OPF/PMMA cage system showed improvement and mechanical stability in a flexion motion. The results demonstrated that the formulation and technique presented in the current study have the potential to improve surgical outcomes in minimally invasive procedures on the spine.

Fgf4 is critical for maintaining Hes7 levels and Notch oscillations in the somite segmentation clock

During vertebrate development, the presomitic mesoderm (PSM) is periodically segmented into somites, which will form the segmented vertebral column and associated muscle, connective tissue, and dermis. The periodicity of somitogenesis is regulated by a segmentation clock of oscillating Notch activity. Here, we examined mouse mutants lacking only Fgf4 or Fgf8, which we previously demonstrated act redundantly to prevent PSM differentiation. Fgf8 is not required for somitogenesis, but Fgf4 mutants display a range of vertebral defects. We analyzed Fgf4 mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 controls Notch pathway oscillations through the transcriptional repressor, HES7. This hypothesis is supported by demonstrating a genetic synergy between Hes7 and Fgf4, but not with Fgf8. Thus, Fgf4 is an essential Notch oscillation regulator and potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.

Yq Microdeletion in a Patient with VACTERL Association and Shawl Scrotum with Bifid Scrotum: A Real Pathogenetic Association or a Coincidence?

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.