Presence Of Genetic Anomalies Research Articles

Neurophysiological Assessment in Children with Vocal Fold Paralysis: A Tertiary Center Experience.

The aim of this study is to report on experience acquired during the laryngeal electrophysiological assessment with Co-MEP and L-EMG in pediatric patients with acquired, congenital, and syndromic vocal fold paralysis (VFP), and correlate our findings with patients' characteristics, their comorbidities, and VFP etiology. Pediatric patients with suspected or previously diagnosed unilateral or bilateral VFP underwent electrophysiological records under general anesthesia; corticobulbar motor-evoked potentials (Co-MEPs) and laryngeal electromyography (L-EMG) of thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were recorded. Statistical analysis revealed a statistically significant correlation between early gestational age at childbirth and TA muscle intensity (p = 0.002) and PCA muscle intensity (p = 0.002); tracheostomy presence and TA muscle intensity (p = 0.002) and PCA muscle intensity (p = 0.002); presence of genetic anomalies with intensity and latency for TA muscle and latency for PCA muscle (TA latency p = 0.015, TA intensity p = 0.021, PCA latency p = 0.035); congenital presentation of VFP and an increased intensity for TA muscle (p = 0.04); latency and intensity for TA muscle (p = 0.024); TA muscle intensity and PCA intensity (p = 0.005). Intraoperative Co-MEPs and L-EMG are two complementary tools for evaluating the functional integrity of the structures involved in conveying signals from the motor cortex to TA and PCA muscles in children with vocal fold paralysis. Further studies are needed to establish their ability to predict the recovery of VF mobility, which could potentially lead to decannulation. Level 4 Laryngoscope, 2024.

Motor Developmental Delay After Cardiac Surgery in Children With a Critical Congenital Heart Defect: A Systematic Literature Review and Meta-analysis.

To systematically review evidence regarding the severity and prevalence of motor development in children with a critical congenital heart defect (CCHD) without underlying genetic anomalies. Twelve percent of all included studies reported abnormal mean motor developmental scores, and 38% reported below average motor scores. Children with single-ventricle physiology, especially those with hypoplastic left heart syndrome, had the highest severity and prevalence of motor delay, particularly at 0 to 12 months. Most included studies did not differentiate between gross and fine motor development, yet gross motor development was more affected. We recommend clinicians differentiate between the type of heart defect, fine and gross motor development, and the presence of genetic anomalies. Furthermore, increased knowledge about severity and prevalence will enable clinicians to tailor their interventions to prevent motor development delays in CCHD.

Recurrent miscarriage and fetal congenital malformations: Is there a neglected causal association?

ObjectiveThe aim of the present study is to investigate the correlation between pregnancies complicated by morphological or chromosomal fetal anomalies and an obstetric history of two or more pregnancy losses, analyzing the association with any maternal risk factor. Study DesignRetrospective analysis of women who had access to the Day Hospital Clinic of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 2012 to 2018 for a pregnancy complicated by fetal malformation and/or abnormal karyotype, and who had an obstetric history of at least one pregnancy loss. Patients were divided into four groups depending on the number of miscarriages and the presence of a genetic anomaly: Group 0 included women with <2 miscarriages and fetal malformations, Group 1 included women with ≥2 miscarriages and fetal malformations, Group 2 included women with <2 abortion, fetal malformations and the presence of genetic anomalies; Group 3 included women with 2 ≥ abortions, fetal malformations and genetic anomalies.Statistical analysis was performed using the SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA). ResultsA total of 466 patients were included in the present analysis. Out of these, 379 patients belonged to Group 0; 40 patients entered in Group 1; Group 2 included 42 patients, and 5 patients were part of Group 3. Pregnancies complicated by fetal congenital malformations in patients with two or more pregnancy losses were significantly associated with maternal trombophilic disease and previous birth defects. Recurrent miscarriage and fetal structural anomalies were also significantly correlated with advanced maternal age. ConclusionsAn adequate periconceptional counseling regarding the risk of fetal congenital anomalies may be indicated in patients affected by thrombophilic disease, as well as in those of advanced maternal age and with a pregnancy history of fetal malformations. The screening for thrombophilia may be advisable in patients with an obstetric history of congenital birth defects.

Early and Midterm Outcomes in High-risk Single-ventricle Patients: Hybrid Vs Norwood Palliation

Although overall outcomes have improved for single-ventricle patients, substantial morbidity and mortality remain for certain high-risk groups. The hybrid stage I procedure is an alternative to the Norwood operation for stage I palliation, but it remains unclear whether it is associated with improved outcomes in high-risk patients. This single-center, nested, case-control study included high-risk patients with a systemic right ventricle who underwent hybrid stage I or Norwood palliation from January 2000 to December 2016. High-risk features included prematurity < 34 weeks, birth weight < 2.5 kg, restrictive/intact atrial septum, at least moderate atrioventricular valve regurgitation or right ventricular dysfunction, genetic or extracardiac anomalies, or left ventricular sinusoids. Patients were matched by presence of genetic anomaly, restrictive/intact atrial septum, and prematurity/weight < 2 kg. Early and midterm outcomes were compared in the matched hybrid vs Norwood groups. The study included 96 patients (35 hybrid, 61 Norwood). Despite improved 30-day survival in hybrid patients (91% vs 66%, P < .01), 1-year survival was similar between the hybrid and Norwood groups (46% vs 48%, P= .9). No hybrid patients required dialysis or extracorporeal membrane oxygenation after stage I palliation as compared with 19% and 22% of Norwood patients, respectively (both P < .01). Hybrid patients, however, required more unplanned reinterventions (43% vs 21%, P= .02). There remains significant morbidity and mortality among high-risk single-ventricle infants. Despite an early survival benefit, hybrid stage I palliation has not been associated with improved midterm outcomes at our center.

Genetic alterations in periprosthetic soft-tissue masses from patients with metal-on-metal hip replacement

Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing.Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement.

Identifying genes involved in regulating differentiation of neuroblastoma cells.

The genes regulating the induction of differentiation in neurons are not definitively known. Some neuronal tumors retain the ability to differentiate into mature, functional neurons in response to pharmacological agents, despite the presence of genetic anomalies. We hypothesized that some of the genes whose expression is altered between undifferentiated and differentiated states may be those responsible for inducing differentiation. To investigate this, we used a mouse neuroblastoma (NB) cell line, NBP(2), in which > or =90% of the cells in the culture terminally differentiate upon elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. Gene expression was analyzed using cDNA array blots containing 588 known genes. mRNA from cultures of undifferentiated and differentiated NB cells was used to make cDNA probes for blot hybridization. We identified several genes that are predominantly expressed in either undifferentiated or differentiated NB cells. In addition, numerous genes are moderately up- or down-regulated during differentiation of NB cells. We identified the N-myc protooncogene, cyclin B1, and protease nexin 1 as genes that are expressed in undifferentiated NB cells and whose levels are significantly down-regulated upon differentiation. In contrast, the c-fes and c-fos protooncogenes and the RAG-1 gene activator are genes whose expression is significantly up-regulated during differentiation of NB cells. These findings were confirmed by RT-PCR analysis. The transcript size and expression level of N-myc, cyclin B1, protease nexin 1, c-fes, and c-fos were verified by Northern blotting. These genes may represent key mediators involved in the regulation of NB cell differentiation.