Postnatal Cases Research Articles

Prenatal Phenotypic Analysis of Branchio-Oto-Renal Spectrum Disorder Attributable to EYA1 Gene Pathogenic Variants and Systematic Literature Review.

Branchio-oto-renal (BOR) spectrum disorders are linked to pathogenic variants in the EYA1 gene, presenting significant challenges for prenatal ultrasound screening due to their phenotypic variability and complexity. Understanding these disorders' phenotypic expressions and genetic foundations is crucial. Our study included pregnant women who underwent fetal whole-exome sequencing at the Department of Medical Genetics and Prenatal Diagnosis, The Third Affiliated Hospital of Zhengzhou University, Henan, China between January 2023 and March 2024. We identified a novel EYA1 gene pathogenic variant and conducted a systematic literature review of all reported prenatal cases associated with EYA1-related diseases, focusing on the detectability of these conditions in prenatal ultrasound. Additionally, we systematically reviewed case reports related to the EYA1 gene, emphasizing missense pathogenic variants for functional predictions and locus position analysis. Our research discovered a new pathogenic variant within the EYA1 gene, highlighting the difficulty of detecting BOR spectrum disorder phenotypes through prenatal ultrasound due to their subtle manifestations. We found that amniotic fluid anomalies and cardiac abnormalities are more prevalent in prenatal cases compared to postnatal cases. A critical region within the EYA Homologous Region (eyaHR) was identified, where missense pathogenic variants significantly affect protein stability, indicating a crucial area associated with the severity of phenotypic expression in EYA1 gene-associated disorders. This study enhances the understanding of the genetic landscape of BOR spectrum disorders and suggests that certain phenotypic markers and genetic regions may be pivotal in improving prenatal screening and diagnosis for EYA1-related diseases.

Chromosome 15q11-q13 Duplication Syndrome: A Review of the Literature and 14 New Cases.

The 15q11.2q13 chromosomal region is particularly susceptible to chromosomal rearrangements due to low-copy repeats (LCRs) located inside this area. Specific breakpoints (BP1-BP5) that lead to deletions and duplications of variable size have been identified. Additionally, this specific region contains several imprinted genes, giving rise to complex syndromes (Prader-Willi, Angelman and 15q11-q13 duplication syndromes). 15q11.2-q13 duplication syndrome has been associated with neurodevelopmental disorders (hypotonia, developmental delay, speech delay and seizures) and ASD but is characterized by variable expressivity and reduced penetrance, features that make genetic counseling a complex procedure especially in prenatal cases. In the present study, a total of 14 pre- and postnatal cases were diagnosed as 15q11.2q13 duplication carriers using Affymetrix CytoScan 750 K array-CGH, and our analysis combined these with 120 cases existing in the literature. The inheritance pattern of the cases of this study is unknown, but as a review of the literature revealed, 62.96% of the affected carriers inherited the duplicated area from their mother. The combined results of this analysis (the present study and the literature) show that in the majority of the cases, the phenotype is a compound phenotype, with clinical characteristics that include ASD, intellectual disability, developmental delay and an absence of speech. The aim of this paper is to deliver new possibilities to genetic counseling that can be provided in prenatal and postnatal cases as the phenotype of 15q11.2q13 microduplication carriers cannot be fully predicted; so, clinical diagnoses should be a combination of molecular findings and clinical manifestations that are present.

Evaluation of a Computer-Aided Clinical Decision Support System for Point-of-Care Use in Low-Resource Primary Care Settings: Acceptability Evaluation Study.

A clinical decision support system (CDSS) based on the logic and philosophy of clinical pathways is critical for managing the quality of health care and for standardizing care processes. Using such a system at a point-of-care setting is becoming more frequent these days. However, in a low-resource setting (LRS), such systems are frequently overlooked. The purpose of the study was to evaluate the user acceptance of a CDSS in LRSs. The CDSS evaluation was carried out at the Jimma Health Center and the Jimma Higher Two Health Center, Jimma, Ethiopia. The evaluation was based on 22 parameters organized into 6 categories: ease of use, system quality, information quality, decision changes, process changes, and user acceptance. A Mann-Whitney U test was used to investigate whether the difference between the 2 health centers was significant (2-tailed, 95% CI; α=.05). Pearson correlation and partial least squares structural equation modeling (PLS-SEM) was used to identify the relationship and factors influencing the overall acceptance of the CDSS in an LRS. On the basis of 116 antenatal care, pregnant patient care, and postnatal care cases, 73 CDSS evaluation responses were recorded. We found that the 2 health centers did not differ significantly on 16 evaluation parameters. We did, however, detect a statistically significant difference in 6 parameters (P<.05). PLS-SEM results showed that the coefficient of determination, R2, of perceived user acceptance was 0.703. More precisely, the perceived ease of use (β=.015, P=.91) and information quality (β=.149, P=.25) had no positive effect on CDSS acceptance but, rather, on the system quality and perceived benefits of the CDSS, with P<.05 and β=.321 and β=.486, respectively. Furthermore, the perceived ease of use was influenced by information quality and system quality, with an R2 value of 0.479, indicating that the influence of information quality on the ease of use is significant but the influence of system quality on the ease of use is not, with β=.678 (P<.05) and β=.021(P=.89), respectively. Moreover, the influence of decision changes (β=.374, P<.05) and process changes (β=.749, P<.05) both was significant on perceived benefits (R2=0.983). This study concludes that users are more likely to accept and use a CDSS at the point of care when it is easy to grasp the perceived benefits and system quality in terms of health care professionals' needs. We believe that the CDSS acceptance model developed in this study reveals specific factors and variables that constitute a step toward the effective adoption and deployment of a CDSS in LRSs.

Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases

BackgroundDistal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance.MethodsWe identified cases of distal Xq28 duplication (chrX: 154,126,575–154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication.ResultsOur search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200–300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males.ConclusionOur study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.

Chromosomal microarray testing yield in 829 cases of microcephaly: a clinical characteristics-based analysis for prenatal and postnatal cases

IntroductionMicrocephaly, characterized by abnormal head growth, can often serve as an initial indicator of congenital, genetic, or acquired disorders. In this study, we sought to evaluate the effectiveness of chromosomal microarray (CMA) testing in detecting abnormalities in both prenatal and postnatal cases of microcephaly.Materials and methodsCMA Testing: We conducted CMA testing on 87 prenatally-detected microcephaly cases and 742 postnatal cases at a single laboratory. We evaluated the CMA yield in relation to specific clinical characteristics.ResultsIn prenatal cases, pathogenic and likely pathogenic (LP) results were identified in 4.6% of cases, a significantly higher rate compared to low-risk pregnancies. The male-to-female ratio in this cohort was 3, and the CMA yield was not influenced by gender or other clinical parameters. For postnatal cases, the CMA yield was 15.0%, with a significantly higher detection rate associated with dysmorphism, hypotonia, epilepsy, congenital heart malformations (CHM), learning disabilities (LD), and a history of Fetal growth restriction (FGR). No specific recurrent copy number variations (CNVs) were observed, and the rate of variants of unknown significance was 3.9%.ConclusionsThe yield of CMA testing in prenatal microcephaly is lower than in postnatal cases (4.6% vs. 15%). The presence of microcephaly, combined with dysmorphism, hypotonia, epilepsy, CHD, LD, and FGR, significantly increases the likelihood of an abnormal CMA result.

Healthcare waste generation and quantification in public health centres in Addis Ababa, Ethiopia.

Healthcare waste produced in healthcare activities entails higher risk of infection and injuries than municipal waste. In developing countries healthcare waste has not received much attention and has been disposed of together with municipal wastes. Modern method of disposal of healthcare waste have been introduced to most healthcare institutions mismanagement and increased in production in public health centres in Ethiopia is important issues. The aim of the study was to assess the type of healthcare waste generation and quantification in selected public health centres in Addis Ababa, Ethiopia. An institution based cross-sectional study were conducted from January to February 2018. Fifteen health centres in Addis Ababa City Administration were selected for this study. Data were collected by using by different color plastic bags (Black plastic bags for non-hazardous wastes, Yellow plastic bags for hazardous wastes and Yellow safety box for needles and Red bags for pharmaceutical wastes and toxic wastes). The collected wastes were measured by weighing scale and were written to data entry sheet. To assure the data quality calibration of weighing scale was made by the standard weight every morning. EPI INFO TM7 and IBM SPSS were used for data entry, cleaning and analysis. The mean healthcare waste generation was 10.64+5.79Kg/day of which 37.26% (3.96+2.20Kg/day) was general waste and 62.74% (6.68+4.29) was hazardous waste from the studies health centres. Total hazardous waste; sharps, infectious, pathological and pharmaceutical wastes constitutes mean (±SD) 0.97 ±1.03, 3.23 ± 2.60, 2.17±1.92 and 0.25 ±0.34 kg/day respectively. Healthcare waste 29.93% and 0.32% were generated from delivery and post-natal case team and nutrition and growth monitoring case team respectively. The annual mean+ SD of healthcare waste generation rate per health centres were 3807.53+ 2109.84 Kg/year. The finding in this study showed there was an increased in hazardous healthcare waste in amount as compared to the WHO standard 85% non-hazardous waste and 10% hazardous waste and 5% toxic wastes. The healthcare waste management practices about segregation, collection, transportation and disposal at the source is crucial to decrease in quantity. Generally unselective handling and disposal of healthcare wastes is a concern.

Incremental yield of whole-genome sequencing over chromosomal microarray analysis and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis.

First, to determine the incremental yield of whole-genome sequencing (WGS) over quantitative fluorescence polymerase chain reaction (QF-PCR)/chromosomal microarray analysis (CMA) with and without exome sequencing (ES) in fetuses, neonates and infants with a congenital anomaly that was or could have been detected on prenatal ultrasound. Second, to evaluate the turnaround time (TAT) and quantity of DNA required for testing using these pathways. This review was registered prospectively in December 2022. Ovid MEDLINE, EMBASE, MEDLINE (Web of Science), The Cochrane Library and ClinicalTrials.gov databases were searched electronically (January 2010 to December 2022). Inclusion criteria were cohort studies including three or more fetuses, neonates or infants with (i) one or more congenital anomalies; (ii) an anomaly which was or would have been detectable on prenatal ultrasound; and (iii) negative QF-PCR and CMA. In instances in which the CMA result was unavailable, all cases of causative pathogenic copy number variants > 50 kb were excluded, as these would have been detectable on standard prenatal CMA. Pooled incremental yield was determined using a random-effects model and heterogeneity was assessed using Higgins' I2 test. Subanalyses were performed based on pre- or postnatal cohorts, cases with multisystem anomalies and those meeting the NHS England prenatal ES inclusion criteria. A total of 18 studies incorporating 902 eligible cases were included, of which eight (44.4%) studies focused on prenatal cohorts, incorporating 755 cases, and the remaining studies focused on fetuses undergoing postmortem testing or neonates/infants with congenital structural anomalies, constituting the postnatal cohort. The incremental yield of WGS over QF-PCR/CMA was 26% (95% CI, 18-36%) (I2 = 86%), 16% (95% CI, 9-24%) (I2 = 85%) and 39% (95% CI, 27-51%) (I2 = 53%) for all, prenatal and postnatal cases, respectively. The incremental yield increased in cases in which sequencing was performed in line with the NHS England prenatal ES criteria (32% (95% CI, 22-42%); I2 = 70%) and in those with multisystem anomalies (30% (95% CI, 19-43%); I2 = 65%). The incremental yield of WGS for variants of uncertain significance (VUS) was 18% (95% CI, 7-33%) (I2 = 74%). The incremental yield of WGS over QF-PCR/CMA and ES was 1% (95% CI, 0-4%) (I2 = 47%). The pooled median TAT of WGS was 18 (range, 1-912) days, and the quantity of DNA required was 100 ± 0 ng for WGS and 350 ± 50 ng for QF-PCR/CMA and ES (P = 0.03). While WGS in cases with congenital anomaly holds great promise, its incremental yield over ES is yet to be demonstrated. However, the laboratory pathway for WGS requires less DNA with a potentially faster TAT compared with sequential QF-PCR/CMA and ES. There was a relatively high rate of VUS using WGS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Analysis of potential copy-number variations and genes associated with first-trimester missed abortion

BackgroundCopy number variation sequencing (CNV-seq) was proven to be a highly effective tool in studying of chromosomal copy number variations (CNVs) in prenatal diagnosis and post-natal cases with developmental abnormalities. However, the overall characteristics of missed abortion (MA) CNVs were largely unexplored. MethodsWe retrospectively analyzed the results of CNV-seq in first-trimester MA. The samples included were single pregnancy loss before 13 gestational weeks, and other potential factors affecting embryonic implantation and development had been excluded. Gene ontology and KEGG enrichment analysis was performed on the smallest overlapping regions (SORs) of high-frequency deletion/duplication. ResultOn the basis of strict inclusion and exclusion criteria, only 152 samples were included in our study. 77 (50.7%) samples displayed chromosome number abnormalities, 32 (21%) showed isolated CNVs, and 43 (28.3%) showed no CNVs. A total of 45 CNVs, ranging in size between 300 Kb and 126.56 Mb were identified, comprising 13 segmental aneuploidies CNVs, and 32 submicroscopic CNVs. Among these CNVs, we screened out four SORs (5q31.3, 5p15.33-p15.2, 8p23.3-p23.2, and 8q22.2–24.3), which were potentially associated with first-term MA. 16 genes were identified as potential miscarriage candidate genes through gene-prioritization analysis, including three genes (MYOM2, SDHA and TPPP) critical for embryonic heart or brain development. ConclusionWe identified some potential candidate CNVs and genes associated with first-trimester MA. 5q31.3 duplications, 5p15.33-p15.2 deletions, 8p23.3-p23.2 deletions and 8p22.2-p24.3 duplications are four potential candidate CNVs. Additionally, MYOM2, SDHA and TPPP are potential genes associated with first-trimester MA.

Onset of Chiari type 1 malformation: insights from a small series of intrauterine MR imaging cases.

Morphometric studies on idiopathic Chiari malformation type 1 (CM1) pathogenesis have been mainly based on post-natal neuroimaging. Prenatal clues related to CM1 development are lacking. We present pre- and post-natal imaging time course in idiopathic CM1 and assess fetal skull and brain biometry to establish if clues about CM1 development are present at fetal age. Multicenter databases were screened to retrieve intrauterine magnetic resonance (iuMR) of children presenting CM1 features at post-natal scan. Syndromes interfering with skull-brain growth were excluded. Twenty-two morphometric parameters were measured at fetal (average 24.4weeks; range 21 to 32) and post-natal (average 15.4months; range 1 to 45) age; matched controls were included. Among 7000 iuMR cases, post-natal scans were available for 925, with postnatal CM1 features reported in seven. None of the fetuses presented CM1 features. Tonsillar descent was clear at a later post-natal scan in all seven cases. Six fetal parameters resulted to be statistically different between CM1 and controls: basal angle (p = 0.006), clivo-supraoccipital angle (p = 0.044), clivus' length (p = 0.043), posterior cranial fossa (PCF) width (p = 0.009), PCF height (p = 0.045), and PCFw/BPDb (p = 0.013). Postnatally, only the clivus' length was significant between CM1 cases and controls. Pre- and post-natal CM1 cases did not share striking common features, making qualitative prenatal assessment not predictive; however, our preliminary results support the view that some of the pathogenetic basis of CM1 may be embedded to some extent already in intrauterine life.

A single group trial (before - after) on impact of physiotherapeutic intervention package on relief from low back pain of pregnant women.

More than half of the women have low back pain (LBP) at some point during pregnancy; the intensity of back pain increases as the pregnancy progresses. Such changes increase their risk for musculoskeletal disorders and fall injuries. Our study's objective was to estimate the prevalence of LBP in antenatal and postnatal cases of pregnancy in PGIMER, Chandigarh and to ascertain impact of a training intervention on incidence and severity of LBP in the study subjects. A single group trial (before and after) on impact of physiotherapeutic intervention package on relief from LBP in pregnant women in between 20 and 35 years of age group were selected. The study duration was one year. The numeric pain rating scale was taken for measuring pain intensity at different levels. Where 0 indicates no pain, 1-3 indicates mild pain (which may be nagging, annoying, and interfering little with activities of daily livings (ADLs)), 4-6 indicates moderate pain (interferes significant with ADLs), and 7-10 indicates severe pain (Disabling, unable to perform ADLs). As per available time, it was decided to include at least 30 subjects in the study. Initially 45 patients were enrolled. Of those, 30 patients were suffering from backache, that is, 67% of the total and 33% did not have any backache. There were no backaches reported in the first trimester, five cases were in the second trimester, and 18 cases were in the third trimester. Of 30 patients, 11 were less than 25 years of age and remaining 19 patients were in the age group of 26-35 years.

MP18-18 WHAT IF THEY CONTINUED THE PREGNANCY? USING PRENATAL ULTRASOUND FINDINGS TO PREDICT POSTNATAL OUTCOMES FOR FETUSES WITH LOWER URINARY TRACT OBSTRUCTION (LUTO) TO IMPROVE COUNSELING AND AID IN DECISION MAKING

You have accessJournal of UrologyCME1 Apr 2023MP18-18 WHAT IF THEY CONTINUED THE PREGNANCY? USING PRENATAL ULTRASOUND FINDINGS TO PREDICT POSTNATAL OUTCOMES FOR FETUSES WITH LOWER URINARY TRACT OBSTRUCTION (LUTO) TO IMPROVE COUNSELING AND AID IN DECISION MAKING Juliane Richter, Shiri Shinar, Lauren Erdman, Hayley Good, Jin K. Kim, Joana Dos Santos, Natasha Brownrigg, Adree Khondker, Priyank Yadav, Michael Chua, Tim van Mieghem, Mandy Rickard, and Armando J. Lorenzo Juliane RichterJuliane Richter More articles by this author , Shiri ShinarShiri Shinar More articles by this author , Lauren ErdmanLauren Erdman More articles by this author , Hayley GoodHayley Good More articles by this author , Jin K. KimJin K. Kim More articles by this author , Joana Dos SantosJoana Dos Santos More articles by this author , Natasha BrownriggNatasha Brownrigg More articles by this author , Adree KhondkerAdree Khondker More articles by this author , Priyank YadavPriyank Yadav More articles by this author , Michael ChuaMichael Chua More articles by this author , Tim van MieghemTim van Mieghem More articles by this author , Mandy RickardMandy Rickard More articles by this author , and Armando J. LorenzoArmando J. Lorenzo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003238.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: LUTO is a chronic condition with a spectrum of outcomes. It is usually suspected prenatally based on ultrasound features (USF). Given the unknown postnatal trajectory and the potential for significant morbidity and mortality, many families choose termination of pregnancy (TOP), often based on USF alone. We sought to develop a tool that can be used to predict postnatal outcomes based on combinations of USF to aid with prenatal counselling and parental decision making. METHODS: We reviewed a LUTO database from a high-risk fetal center and tertiary pediatric center and collected USF and postnatal need for urinary diversion and renal replacement therapy (RRT). USFs from a gestational age (GA) of 13-26 weeks for TOPs were collected and matched to fetuses who were not terminated to build a random forest model. Each predictor was assessed independently with combined importance when accounting for other predictors (see Table 1). The model was used to predict the most likely postnatal outcomes for TOPs had the pregnancy been continued. RESULTS: USF from 37 TOPs and 30 livebirths with postnatally confirmed LUTO were included with a follow up time of 1599 days. There were 4 postnatal deaths. Dialysis was predicted with the highest accuracy of 81% (63% sensitivity, 89% specificity), with transplant second highest (69%, 43% sensitivity, 79% specificity), and diversion the least well predicted (50% accuracy). For TOPs, had the pregnancies continued, the model predicted dialysis in 16/37 (43%), transplant in 7/37 (19%) cases, and urinary diversion in 17/37 (46%). All TOPs predicted to receive transplant were predicted to receive diversion and/or dialysis, with the majority receiving both (5/7). This is similar to the postnatal LUTO cases in which 6/7 transplanted cases received both diversion and dialysis. CONCLUSIONS: Our data suggests that it is possible to predict postnatal renal replacement therapy from USFs in TOPs had the pregnancy been continued. Predictive accuracy will improve with continued follow-up of more patients, enabling more personalized prenatal counseling and allowing for more informed decision making for families. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e230 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juliane Richter More articles by this author Shiri Shinar More articles by this author Lauren Erdman More articles by this author Hayley Good More articles by this author Jin K. Kim More articles by this author Joana Dos Santos More articles by this author Natasha Brownrigg More articles by this author Adree Khondker More articles by this author Priyank Yadav More articles by this author Michael Chua More articles by this author Tim van Mieghem More articles by this author Mandy Rickard More articles by this author Armando J. Lorenzo More articles by this author Expand All Advertisement PDF downloadLoading ...

Coexisting Conditions Modifying Phenotypes of Patients with 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder with an extremely broad phenotypic spectrum. The aim of our study was to investigate how often the additional variants in the genome can affect clinical variation among patients with the recurrent deletion. To examine the presence of additional variants affecting the phenotype, we performed microarray in 82 prenatal and 77 postnatal cases and performed exome sequencing in 86 postnatal patients with 22q11.2DS. Within those 159 patients where array was performed, 5 pathogenic and 5 likely pathogenic CNVs were identified outside of the 22q11.2 region. This indicates that in 6.3% cases, additional CNVs most likely contribute to the clinical presentation. Additionally, exome sequencing in 86 patients revealed 3 pathogenic (3.49%) and 5 likely pathogenic (5.81%) SNVs and small CNV. These results show that the extension of diagnostics with genome-wide methods can reveal other clinically relevant changes in patients with 22q11 deletion syndrome.

Multisite Assessment of Optical Genome Mapping for Analysis of Structural Variants in Constitutional Postnatal Cases

This study compares optical genome mapping (OGM) performed at multiple sites with current standard-of-care (SOC) methods used in clinical cytogenetics. This study included 50 negative controls and 359 samples from individuals (patients) with suspected genetic conditions referred for cytogenetic testing. OGM was performed using the Saphyr system and Bionano Access software version 1.7. Structural variants, including copy number variants, aneuploidy, and regions of homozygosity, were detected and classified according to American College of Medical Genetics and Genomics guidelines. Repeated expansions in FMR1 and contractions in facioscapulohumeral dystrophy 1 were also analyzed. OGM results were compared with SOC for technical concordance, clinical classification concordance, intrasite and intersite reproducibility, and ability to provide additional, clinically relevant information. Across five testing sites, 98.8% (404/409) of samples yielded successful OGM data for analysis and interpretation. Overall, technical concordance for OGM to detect previously reported SOC results was 99.5% (399/401). The blinded analysis and variant classification agreement between SOC and OGM was 97.6% (364/373). Replicate analysis of 130 structural variations was 100% concordant. On the basis of this demonstration of the analytic validity and clinical utility of OGM by this multisite assessment, the authors recommend this technology as an alternative to existing SOC tests for rapid detection and diagnosis in postnatal constitutional disorders.

Molecular cytogenetic and phenotypic characterization of Phelan McDermid and 22q13 duplication syndrome: a case report

BackgroundPhelan-McDermid syndrome (PHMDS) is a rare genetic disorder mostly caused by haploinsufficincy of SHANK3 gene, and characterized by neonatal hypotonia, developmental delay, minor dysmorphic features, seizures and behavior problems. Literature of this syndrome is scanty and confusing, and represents a challenge for pediatricians, in terms of finding the correct diagnoses.Case presentationIn a postnatal case with hypotonia and dysmorphic features a de novo ring chromosome r(22) leading to in parallel microdeletion and micro duplication in 22q13 was diagnosed by banding cytogenetics, and further characterized in detail by molecular cytogenetic and chromosomal microarray.ConclusionHere a rare PHMDS case caused by a r(22) is presented. Less than 10 comparable cases are reported in the literature. The present case highlights the importance of conducting genetic counseling and appropriate genetic tests for newborns with mild dysmorphic features.

Personalized health risk assessment based on single-cell RNA sequencing analysis of a male with 45, X/48, XYYY karyotype

Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband’s long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient.

Microduplication 3p26.3p24.3 and 4q34.3q35.2 Microdeletion Identified in a Patient with Developmental Delay Associated with Brain Malformation.

Microdeletions and microduplications are involved in many of prenatal and postnatal cases of multiple congenital malformations (MCM), developmental delay/intellectual disability (DD/ID), and autism spectrum disorders (ASD). Molecular karyotyping analysis (MCA), performed by DNA microarray technology, is a valuable method used to elucidate the ethology of these clinical expressions, essentially contributing to the diagnosis of rare genetic diseases produced by DNA copy number variations (CNVs). MCA is frequently used as the first-tier cytogenetic diagnostic test for patients with MCM, DD/ID, or ASD due to its much higher resolution (≥10×) for detecting microdeletions and microduplications than classic cytogenetic analysis by G-banded karyotyping. Therefore, MCA can detect about 10% pathogenic genomic imbalances more than G-banded karyotyping alone. In addition, MCA using the Single Nucleotide Polymorphism-array (SNP-array) method also allows highlighting the regions of loss of heterozygosity and uniparental disomy, which are the basis of some genetic syndromes. We presented a case of a five-year-old patient, with global development delay, bilateral fronto-parietal lysencephaly, and pachygyria, for which MCA through SNP-Array led to the detection of the genetic changes, such as 3p26.3p24.3 microduplication and 4q34.3q35.2 microdeletion, which were the basis of the patient's phenotype and to the precise establishment of the diagnosis.

USE OF CHECKLIST FOR EARLY RECOGNIZATION AND MANAGEMENT OF POST PARTUM COMPLICATIONS IN IMMEDIATE POSTPARTUM PERIOD

Background: The immediate postnatal period refers to the time just after childbirth, during which the risks to the mother of postpartum haemorrhage and other significant morbidity are highest. Close direct or indirect supervision by a skilled attendant is required in this period so that any problems can be identified promptly and appropriate intervention can be taken. Present study was conducted to assess the usefulness of patient monitoring checklist in reduction of post partum and post surgical adverse events. The objective of the present study is to decrease the adverse events in postnatal cases from 11.70 percent to 3 percent within 8 weeks time. Materials and Methods: A simple checklist was designed according to nine key components of supervision following delivery /caesarean section. Implementation of a checklist was accomplished following resident doctors and nurses training over 4 sessions. Measurement Data from all checklists used in the maternity ward were entered into a secure Microsoft Excel database. Deliveries for which a checklist was not filled out were excluded. An endline data was collected after eight weeks to assess the usefulness of checklist in prevention of postpartum adverse events. Results: The adverse event rates were 11.70% for historical controls and 2.70% for checklist cases. There was statistically significant improvement (p value &lt;0.001) in vigilance in monitoring of the postnatal cases. Resident doctors, faculty members and hospital administrators gave a positive feedback about the usefulness of checklist for routine use in obstetric practice. Conclusion: It was found that integrating a post partum monitoring checklist, coaching and intervention with strong leadership support and adherence to QI principles of rapid cycles of change was successful in improving the delivery of quality treatment and was associated with some decline in post partum morbidity and mortality.

Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: A report of 21 cases from a medical center and review of the literature.

Background: Phelan–McDermid syndrome (PMS), caused by deletions at 22q13.3 and pathogenic variants in the SHANK3 gene, is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), dysmorphic features, absence of or delayed language, and other features. Methods: Conventional karyotyping, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) have been used to detect genetic defects causing PMS. We summarized the genetic and clinical findings from prenatal to postnatal stages of detected cases of PMS and mapped potential candidate haploinsufficient genes for deletions of 22q13. This study aimed to summarize the laboratory findings, genetic defects, and genotype–phenotype correlations for Chinese patients with PMS. Results: Seven prenatal cases and fourteen postnatal cases were diagnosed with PMS in our center. Thirteen cases had a deletion ranging in size from 69 to 9.06 Mb at 22q13.2-q13.33, and five cases had a pathogenic variant or an intragenic deletion in the SHANK3 gene. Three familial cases with a parental carrier of a balanced translocation were noted. A review of the literature noted another case series of 29 cases and a report of five cases of PMS in China. Genotype–phenotype correlations confirmed haploinsufficiency of the SHANK3 gene for PMS and suggested other candidate haploinsufficient genes TNFRSFI3C and NFAM1 genes for immunological features and TCF20, SULT4A1, PARVB, SCO2, and UPK3A genes for intellectual impairment and behavioral abnormality, neurological features, macrocephaly/hypotonia, oculopathy, and renal adysplasia, respectively. Conclusion: Indications for prenatal diagnosis of PMS are not specific, and approximately 85% prenatally diagnosed PMS elected termination of pregnancies after genetic counseling. For postnatal cases, 62.5% were caused by a deletion at 22q13 and 37.5% were caused by a pathogenic variant or an intragenic deletion in the SHANK3 gene. Approximately 6.7% of cases with a deletion were familial, and almost all pathogenic variants were de novo. Combined karyotype, CMA, and WES should be performed to increase the diagnostic yield. The identification of other candidate haploinsufficient genes in deletions of 22q13.2-q13.33 could relate to more severe dysmorphic features, neurologic defects, and immune deficiency. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management for the Chinese cases of PMS.

Comparison of Pre- and Postnatally Diagnosed Coronary Artery Fistulae: Echocardiographic Features and Clinical Outcomes

Coronary artery fistulae (CAFs) are abnormal connections of a coronary artery to a cardiac chamber or vessel. There is a paucity of data regarding clinical outcomes, especially when detected prenatally. This was a multicenter retrospective cohort study of all CAF cases from 2002 to 2016. Clinical characteristics and outcomes were compared between the prenatal and postnatal cohorts. A scoping literature review of prenatal CAFs was completed. CAFs were diagnosed prenatally in 12 (median, 23weeks' gestation; interquartile range, 17-36weeks' gestation) and postnatally in 94 (median, 2.8years; interquartile range, 0-15years) cases. Structural heart defects were present in five (42%) prenatal and 19 (20%) postnatal cases (P=.011) and genetic conditions in five (42%) and 14 (15%), respectively (P=.001). CAFs were considered large in 12 (100%) prenatal versus 14 (15%) postnatal cases (P<.001). The CAF distribution was similar between cohorts: 39 (67%) from the left and 19 (33%) from the right coronary artery, with the most common exit sites being the main pulmonary artery 54 (51%), right ventricle 30 (28%), and right atrium 12 (11%). Of prenatal cases, all large at presentation, none progressed, six (50%) resolved by birth, and one (8%) underwent elective neonatal ligation. Of postnatal cases, one presented in cardiogenic shock, and no other case had ventricular dysfunction, arrhythmias, or ischemic changes. Nine (10%) with large shunts underwent intervention (seven percutaneous, two surgical), of whom three were symptomatic. Two (17%) prenatal and two (2%) postnatal cases had coronary abnormalities, two with normal results on stress perfusion imaging. Postnatal death occurred in two (17%) prenatal and four (4%) postnatal cases (P=.05). Of the total 36 prenatal cases reported in the literature, including the 12 cases in the present series, 10 (28%) had clinical symptoms at birth, including three (8%) with cardiogenic shock, and 19 (53%) underwent intervention. Prenatally and postnatally encountered CAFs are associated with a good prognosis for most, with many not requiring intervention. Although half of the prenatal CAFs resolved prenatally, given the risk for cardiogenic shock at birth and heart failure in early infancy, appropriate perinatal planning and postnatal surveillance is warranted.

Optimizing care and consultation in trisomy 13 and 21

The paradigm that infants with trisomy 13 (T13) or trisomy 18 (T18) do not benefit from supportive care was driven largely by a dearth of data surrounding if and how survival outcomes change with medical and/or surgical intervention. In this volume, Coretzzo et al. assess outcomes in and characteristics of a retrospective cohort of pre- and post-natal cases of T13 and T18 using a population-based and multi-centered approach.