Trisomy Research Articles

Cleft lip and/or palate mortality trends in the USA: a retrospective population-based study

BackgroundCleft lip and/or palate (CL/P) is one of the most common congenital anomalies worldwide. Although CL/P management may require a series of interventions, mortality resulting from CL/P alone is rare....

Síndrome de Edwards e Patau em um hospital universitário: além do paliativo

ABSTRACT Objective: To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes. Methods: Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied. Results: 33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30–36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2–304) and 25 days (13–58), respectively. Conclusions: Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.

Mosaicism For Autosomal Trisomies: A Review of The Literature Suggests Inverse Effects of Carriers’ Gender and Maternal Age on Clinical Manifestations

Mosaicism For Autosomal Trisomies: A Review of The Literature Suggests Inverse Effects of Carriers’ Gender and Maternal Age on Clinical Manifestations

Phenotypic and cytogenetic variability of patau syndrome in Morocco.

The objective of this work was to identify phenotypic features and cytogenetic aspects of trisomy 13 in Moroccan population. The retrospective study was conducted on a group of 9 cases diagnosed cytogenetically with trisomy 13. The study of sex ratio showed a slight female dominance in our group of cases. The major clinical findings included: Holoprosencephaly, microphthalmia and anophthalmia, coloboma of iris, cleft lip and palate, nasal and ear abnormalities, retrognathism and sloping forehead, polydactyly, capillary hemangiomas, omphalocele, congenital heart defect, renal abnormalities, cryptorchidism, language delay. The cytogenetic study showed the dominance of the free and homogeneous trisomy 13 (56%). Patients who have this formula are dead at an early age (does not exceed one month). However, each of the chromosomal formula, trisomy 13 by translocation and partial trisomy 13 t (13;18), was found in 20% of our patients. The partial trisomy 13 t (13;18) is the only variant that is still alive and the patients with this anomaly suffer mainly from renal and cardiac anomalies with slight dysmorphia and psychomotor retardation. Our study shows the interest of the cytogenetic analysis in the diagnosis accuracy and in the genetic counseling of patients with Patau syndrome and their parents.

Value of non-invasive prenatal testing for rare autosomal trisomies in fetuses

To evaluate the value of non-invasive prenatal testing(NIPT)for detecting rare autosomal trisomies in fetuses. We retrospectively analyzed the data of cases with rare autosomal trisomies detected by NIPT in our hospital from January, 2019 to April, 2023.Invasive prenatal diagnostic tests including chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing, and fluorescence in situ hybridization were performed in all the cases after clinical counseling, and their test results and pregnancy outcomes were analyzed. Among 25 282 women receiving NIPT, 56(0.22%)were found to have high risks for rare autosomal trisomies in circulating plasma DNA.Trisomy 7 was the most frequently detected trisomy, accounting for 45% of the total cases(25/56), while trisomies 1, 4, 17, and 19 were not detected.Among the 46 cases with genetic results of the fetuses, 10 were identified to have true fetal mosaicism.The overall positive predictive value of NIPT was 22%(10/46)for rare autosomal trisomies, and 10% for trisomy 7(2/20).Of the 52 cases followed up for pregnancy outcomes, 33(63%)cases without fetal mosaicism resulted in normal live births, while 10 had unfavorable outcomes including fetal growth restriction, preterm birth, and maternal complications, and among them fetal growth restriction was the most typical and the earliest condition observed in these cases.Among the 22 followed up cases of non-true mosaicism for trisomy 7, 82% resulted in normal live births. NIPT increases the detection rate of true fetal mosaicism but with a low positive predictive value.Most of the cases with non-true mosaicism, particularly trisomy 7, can have favorable outcomes.NIPT can also be useful in identifying causes of fetal growth restriction in the second and third trimesters when invasive prenatal testing does not reveal abnormalities.

Importance of a detailed anomaly scan after a cfDNA test indicating fetal trisomy 21, 18 or 13

ObjectiveTo investigate the effect of the presence or absence of fetal anomalies and soft markers diagnosed by ultrasound on positive predictive value (PPV) 21, 18 and 13 in pregnancies with a high-risk cfDNA result.MethodsRetrospective study including singleton pregnancies with high-risk NIPT results for common trisomies followed by invasive testing. The cases were grouped by gestational age at the time of invasive testing and by the presence or absence of fetal abnormalities or soft markers. The ultrasound was considered abnormal if at least one major defect or a soft marker was detected.ResultsA total of 173 women were included. Median maternal and gestational age was 37.7 years and 14.0 weeks, respectively. CfDNA test result showed high-risk for trisomy 21 and trisomy 18 or 13 in 119 and 54 cases, respectively. The “pre-ultrasound” PPV for trisomy 21 and for trisomy 18 or 13 were 98.3% and 68.4%, respectively. In case of a high-risk result for trisomy 21 and no fetal anomalies, the PPV was 86.7% while it was 100% if there were anomalies or markers present. In the case of a high-risk result for trisomy 18 or 13, the PPV was 9.5% if the ultrasound examination was normal and 100% if the ultrasound examination was abnormal.ConclusionThis study suggests that a detailed ultrasound examination performed after a cfDNA result that is high-risk for one of the common autosomal trisomies adds significantly to establishing an individualized risk assessment. This is particularly true in cases with a high-risk result for trisomies 18 or 13.

Alzheimer’s disease phenotypes in human induced pluripotent stem cell‐based models of Down syndrome

AbstractBackgroundBy age 40, all people with Down syndrome (DS) develop Alzheimer’s disease (AD) brain neuropathology, including Aβ plaques and neurofibrillary tangles of phosphorylated microtubule associated protein tau (MAPT), and most go on to develop early‐onset dementia. People with Down syndrome (DS) have triplication of chromosome 21 (trisomy 21) and they develop AD neuropathology due to triplication of the amyloid precursor protein gene (APP) which resides on chromosome 21. Here, we developed and characterized human induced pluripotent stem cell (hiPSC)‐derived neurons, astrocytes, microglia, and cerebral organoid (CO) models of DS and familial AD and used them to evaluate the AD‐related pathological mechanisms caused by trisomy 21.MethodWe obtained hiPSC lines derived from individuals with DS, healthy control individuals (HC), and individuals with familial AD, including duplication of APP on one chromosome (APPdup) or carrying the London mutation in APP (APPV717I). All donors had the apolipoprotein E (APOE) ε3/ε3 genotype. We generated hiPSC‐derived neurons, astrocytes, microglia, and COs using validated techniques. We evaluated the hiPSC‐derived neural cells and COs at different ages for AD‐related neuropathology, neuroinflammation, and neurodegeneration by performing RNA sequencing, immunohistochemistry, immunoblotting, and enzyme‐linked immunosorbent assay.ResultAD‐related size phenotypes characteristic of neurodegeneration were observed in DS hiPSC‐based models relative to HC models. Dysregulated gene and protein expression of APP, MAPT, and APOE, in addition to chromosome 21 genes, were also observed in DS hiPSC‐based models. In particular, neuroinflammatory markers, especially those previously shown in APOE‐related pathways, were also increased in DS models.ConclusionWe characterized new hiPSC‐based models of DS and familial AD which will be useful for identifying commonalities in disease mechanisms as well as for dissecting the roles of chromosome 21 genes other than APP. We identified several AD‐related phenotypes in hiPSC‐based DS related to neuropathology, neuroinflammation, and neurodegeneration. We expect that these hiPSC‐based models will be useful for testing therapeutics in the future to address AD in people with DS, for which there is no cure.

An accelerated rate of Beta‐amyloid Measured with [C‐11]PiB in Down Syndrome compared to Neurotypical Populations

AbstractBackgroundDown syndrome (DS) is characterized by a higher risk and earlier onset of beta‐amyloid (Aβ) plaque accumulation and Alzheimer’s disease (AD). The triplication of chromosome 21 containing the amyloid precursor protein (APP) gene is implicated in this process and in this study we compare the accumulation rates of Aβ between DS and neurotypical (NT) populations quantified by longitudinal [C‐11]PiB imaged at the same site to minimize experimental variation.MethodsIndividuals with three or more [C‐11]PiB scans spanning eleven years our site with at least one Aβ+ (global SUVR>1.40) and Aβ‐ [C‐11]PiB scan were selected. 12 of 74 DS and 15 of 246 NT participants fit these criteria. An identical imaging procedure was conducted for all participants imaged on either an ECAT HR+ or Biograph mCT PET scanner 50‐70 minutes post‐injection. Reconstructed PET images were summed and spatially normalized into template space and converted into 50‐70min SUVR images using a cerebellar grey matter reference region. Global SUVR composed of grey matter regions from the AAL atlas was used as a metric for Aβ deposition. SUVR data were fit against age with a logistic growth curve (f(t) = NS+K/(1+e(‐r(t‐t50)))) to determine Aβ accumulation as subjects transitioned to Aβ+. The rate of accumulation was found using the slope of the curve at Aβ positivity threshold based on the model fit. Our model fixed NS = 1.12, the average baseline SUVR of all Aβ‐ subject scans (n = 491), and K = 1.28, the highest specific binding in any participant.ResultsPlotting [C‐11]PiB SUVR against age provides visual comparisons of cohorts (Fig 1) and transforming the x‐axis to amyloid chronicity (t = 0 at Aβ+) illustrates differences in accumulation rates between groups (Fig 2). The average rate of amyloid accumulation (ΔSUVR/yr) when becoming Aβ+ in the DS cohort is 0.071(0.021) versus 0.043(0.009) for NT (p = 4.31×10−4).ConclusionsAβ accumulation rate was higher in the DS cohort compared to NT. This is consistent with the additional APP gene copy in DS, and we observed an accumulation rate 65% faster in this cohort. There was a higher variability in the DS population requiring further investigation towards understanding the influence of genetic and lifestyle factors on Aβ deposition.

Significant improvement in survival outcomes of trisomy 18 with neonatal intensive care compared to non-intensive care: a single-center study.

Trisomy 18 syndrome, also known as Edwards syndrome, is a chromosomal trisomy. The syndrome has historically been considered lethal owing to its poor prognosis, and palliative care was primarily indicated for trisomy 18 neonates. Although there have been several reports on the improvement of survival outcomes in infants with trisomy 18 syndrome through neonatal intensive care, few studies have compared the impact of neonatal intensive care on survival outcomes with that of non-intensive care. Therefore, we compared the survival-related outcomes of neonates with trisomy 18 between intensive and non-intensive care. Seventeen infants of trisomy 18 admitted to our center between 2007 and 2019 were retrospectively studied. We divided the patients into a non-intensive group (n = 5) and an intensive group (n = 12) and evaluated their perinatal background and survival-related outcomes of the two groups. The 1- and 3-year survival rates were both 33% in the intensive group, which was significantly higher than that in the non-intensive group (p < 0.001). Half of the infants in the intensive care group were discharged alive, whereas in the non-intensive care group, all died during hospitalization (p = 0.049). Neonatal intensive care for neonates with 18 trisomy significantly improved not only survival rates but also survival-discharge rates. Our findings would be helpful in providing 18 trisomy neonates with standard neonatal intensive care when discussing medical care with their parents.

Indications, types, and diagnostic implications of prenatal genetic testing in Sub-Saharan Africa: A descriptive study.

To describe indications, test types, and results of prenatal diagnostic genetic amniocentesis among Ethiopian pregnant women. This study was a descriptive study on prenatal diagnostic genetic testing among Ethiopian pregnant women with certain indications and it was conducted at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia) from January 2017 to April 2023. Data on sociodemographic characteristics, genetic testing indications, types, and results were collected electronically. Data were analysed using SPSS version 23. A total of 159 cases were analysed. The commonest indication for genetic testing among the study subjects was major fetal structural anomalies identified on specialized prenatal anatomic scanning of the index pregnancy detected in 71(44.7%) cases. Down syndrome and Edward syndrome were the commonest genetic aberrations detected accounting for 6.3% (10/159) and 4.4% (7/159), respectively. Among the rare genetic aberration detected were Di-George syndrome (0.6%) and Duchenne muscular dystrophy (0.6%). Findings of our study underscore the importance of diagnostic prenatal testing in a Sub-Saharan Africa setting, as common (trisomy 21&18) and rare genetic defects were identified using this important prenatal diagnostic testing. Considering the implications of detecting chromosomal abnormalities for future counselling and care, carrier state in parents for some chromosomal anomalies, and planning post-natal management of some abnormalities that are associated with aneuploidies (notably cardiac anomalies), initiation of diagnostic prenatal genetic testing service at tertiary public health facilities should be acted up on.

Airway findings in trisomy 13 and trisomy 18: A 10-year retrospective review.

Trisomy 18 and trisomy 13 are the most common autosomal trisomies following trisomy 21, with overall incidence rising. Both diagnoses are characterized by multisystem involvement and were previously thought to be incompatible with life. New data suggest that prolonged survival is possible, and thus many families are opting for more aggressive medical interventions. This study aims to describe airway findings in trisomy 18 and trisomy 13, as these have not been comprehensively studied and can impact medical decision-making. We hypothesize that most children with trisomy 18 and trisomy 13 will have abnormal findings on airway endoscopy. This a 10-year retrospective analysis of children with trisomy 13 or trisomy 18 who underwent endoscopic airway evaluation at a single center between 2011 and 2021. A total of 31 patients were evaluated. Thirty-one patients were included and underwent flexible bronchoscopy by a pediatric pulmonologist, often in conjunction with rigid bronchoscopy performed by pediatric otolaryngology. Findings were typically complimentary. All patients had at least one clinically significant finding on evaluation, and most patients had both upper and lower airway, as well as static and dynamic airway findings. The most common airway findings in children with trisomy 13 and 18 include tracheomalacia, bronchomalacia, laryngomalacia, hypopharyngeal collapse, glossoptosis, and bronchial compression. These findings can have significant implications for clinical care, and thus knowledge of trends has the potential to improve counseling on expected clinical course, presurgical planning, and informed consent before interventions.

Trisomies Reorganize Human 3D Genome.

Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization.

Prenatal Screening Characteristics of Edward’s and Patau’s Syndrome in the First Trimester at the National Hospital of Obstetrics and Gynecology

Edward and Patau syndromes are severe genetic abnormalities. The consequences of these syndromes are often fatal in the fetus and neonate. Prenatal screening for these syndromes is important for early detection of birth defects. 212 medical records of pregnant women with normal pregnancies were selected using convenience sampling. Selection of 34 cases of Edward or Patau pregnancy using a total sampling technique. We conducted a descriptive retrospective study to describe and compare various markers related to prenatal screening to establish the most appropriate diagnostic criteria. A history of spontaneous abortion is associated with an increased risk of subsequent pregnancies with Edward's or Patau's syndrome. The nuchal translucency value was mainly concentrated below 2 mm, lower than the values observed in Trisomy 18 and 13 cases, predominantly in the 2-3 mm range. A threshold of 2.5 mm for nuchal translucency measurement had the highest detection rate for Edwards and Patau syndromes, and abnormal fetal heart rate was most commonly observed in trisomy cases on ultrasound examination. The MoM fβ-hCG concentration in the Edwards and Patau groups was predominantly concentrated in the low range (≤1), while the normal group showed a higher concentration in the range of 1-3. The MoM PAPP-A concentration in the normal group was commonly found in the range of 0.5-1, which was higher compared to the trisomy group.&#x0D; &#x0D; &#x0D; &#x0D;

Analysis of copy number variations and possible candidate genes in spontaneous abortion by copy number variation sequencing.

Embryonic chromosomal abnormalities represent a major causative factor in early pregnancy loss, highlighting the importance of understanding their role in spontaneous abortion. This study investigates the potential correlation between chromosomal abnormalities and spontaneous abortion using copy number variation sequencing (CNV-seq), a Next-Generation Sequencing (NGS) technology. We analyzed Copy Number Variations (CNVs) in 395 aborted fetal specimens from spontaneous abortion patients by CNV-seq. And collected correlated data, including maternal age, gestational week, and Body Mass Index (BMI), and analyzed their relationship with the CNVs. Out of the 395 cases, 67.09% of the fetuses had chromosomal abnormalities, including numerical abnormalities, structural abnormalities, and mosaicisms. Maternal age was found to be an important risk factor for fetal chromosomal abnormalities, with the proportion of autosomal trisomy in abnormal karyotypes increasing with maternal age, while polyploidy decreased. The proportion of abnormal karyotypes with mosaic decreased as gestational age increased, while the frequency of polyploidy and sex chromosome monosomy increased. Gene enrichment analysis identified potential miscarriage candidate genes and functions, as well as pathogenic genes and pathways associated with unexplained miscarriage among women aged below or over 35 years old. Based on our study, it can be inferred that there is an association between BMI values and the risk of recurrent miscarriage caused by chromosomal abnormalities. Overall, these findings provide important insights into the understanding of spontaneous abortion and have implications for the development of personalized interventions for patients with abnormal karyotypes.

АНАЛІЗ ДИНАМІКИ НАРОДЖЕННЯ ДІТЕЙ З АУТОСОМНИМИ ТРИСОМІЯМИ ПО ХМЕЛЬНИЦЬКІЙ ОБЛАСТІ

In the face of challenging modern demographic conditions, the imperative of preserving human life is becoming increasingly urgent. Environmental pollution, a deteriorating ecological landscape, imbalanced nutrition, unhealthy lifestyles, the accumulation of hereditary defects, and a rising genetic burden collectively exert adverse effects on Ukraine's gene pool. This unfortunate scenario contributes to the increased rate of early child mortality and the birth of children with disabilities [7].&#x0D; The objective of this study was to analyze the trends in child births with Down, Edwards, and Patau syndromes while investigating the influence of maternal age on the incidence of these genetic anomalies in the Khmelnytskyi region from 2017 to 2021.&#x0D; We conducted an analysis of statistical data pertaining to newborns, utilizing information from the Main Statistical Office in the Khmelnytskyi region. This investigation was undertaken in collaboration with the medical and genetic consultation department of the KP "Khmelnytskyi City Perinatal Center." It involved a comprehensive review of outpatient records for patients born with Down, Edwards, and Patau syndromes, aimed at understanding the clinical condition of the infants and the course of pregnancy in their mothers.&#x0D; The analysis revealed that a total of 50,475 babies were born in the region over the course of five years. However, an annual decrease in the birth rate was observed, with an average reduction of 705 children per year. The incidence rate of newborns with Down syndrome, Edwards syndrome, and Patau syndrome ranged from 0.10% to 0.13%. During the research period, 45 children with Down syndrome were born in the Khmelnytskyi region. Cytogenetic analysis indicated that 39 of these children (87 %) had a complete trisomy, 4 had a mosaic form (9 %), and 2 (4 %) had a translocation form. Children with complete trisomy exhibited four or more phenotypic features simultaneously. In the region, 12 children were born with Edwards syndrome, including 9 with complete trisomy and 3 with a mosaic form. No newborns were identified with partial trisomy. Cases included both full-term and premature births, as well as instances of infant mortality. Two children with Patau syndrome were born (1 boy in 2017 and 1 girl in 2019), both with complete trisomy. They were born full-term but with low birth weight and multiple developmental disabilities, with one child surviving for 12 hours and the other for 31 hours.&#x0D; Upon analyzing the age of the parents of the probands, it was discovered that the majority (38 mothers, 64 %) were not within the age risk group for having a child with trisomy. This suggests that women of any age can be at risk of having a child with trisomy. Thus, there is a clear need for medical-genetic counseling and prenatal screening for every pregnant woman during the first trimester of pregnancy.

Late first-trimester ultrasound findings can alter management after high-risk NIPT result.

To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result for various chromosomal abnormalities. This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first-line screening test. Data were collected from pre-NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome-wide analysis for the last 2 years. Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high-risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high-risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. LFTU after a high-risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at-risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high-risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A-331 Prenatal Maternal First Trimester Screening and Establishing the Multiple of Medians of Double Marker Tests in Tertiary Care Hospital in India

Abstract Background Down's syndrome, Edwards syndrome, and Patau syndrome (trisomy 21, 18, 13 respectively) in a fetus can be screened by prenatal testing using the maternal serum. Prenatal testing can provide an accurate assessment of the patient's risk of carrying an affected fetus. Double marker testing which includes the levels of free β- Human Chorionic Gonadotropin and Pregnancy Associated Plasma Protein A in the maternal serum along with the measurement of Crown Rump Length and Nuchal Translucency helps in determining the risk of Trisomy 21. Prenatal testing prevents the need for invasive methods. Methods This is a study conducted in Kokilaben Dhirubhai Ambani Hospital and Research Centre, Mumbai, Maharashtra, India from January 2012 to December 2018 for 628 pregnant women. The data for 1st trimester was divided into 3 groups: 11 to 11.6 weeks(86 patients), 12 to 12.6 weeks (421 patients), and 13 to 13.6 weeks (121 patients) based on their gestational age. This study included the determination of levels of double markers like free β- Human Chorionic Gonadotropin and Pregnancy Associated Plasma Protein A using maternal serum along with the ultrasound studies which included the Crown Rump Length and Nuchal Translucency measurements. Additional factors like a history of chromosomal abnormalities, smoking habits, insulin-dependent diabetes, and other dichotomous markers like the presence of nasal bone, abnormal ductal flow, and tricuspid regurgitation are also considered in calculating the risk. The concentration of biochemical parameters was expressed in Multiple of Median (MOM) with respect to maternal age. The risk assessment was analyzed using SSDW 5 and SSDW 6 software and the cut-off was set at 1:250 for age as well as trisomy 21, 18, and 13. Results The total number of positive patients for trisomy 21 and trisomy 13/18 were represented in percentage which turned out to be 2.86% and 1.11% respectively in association with the gestational age, dichotomous markers, double marker test, and ultrasound studies. The MOM for β-HCG, PAPPA, and NT were compared in SSDW5 and SSDW6. The mean β-HCG MOM negative and positive patients (trisomy 21) were found to be 1.34 ± 0.945 and 2.74 ± 1.685 respectively indicating the levels increase above normal. The mean PAPPA MOM negative and positive patients (trisomy 21) were found to be 1.47 ± 0.9125 and 0.77 ± 7667 respectively indicating the levels decrease below the normal. The NT mom for negative and positive patients was 0.91 ± 1879 and 1.88 ± 1.6508 respectively which suggests that the thickness of nuchal translucency increases with the increased risk for trisomy 21. Conclusion 18 out of 628 patients tested positive for trisomy 21 which was assessed using double marker testing and ultrasound studies. The levels of free β-HCG were seen to be increased and the levels of PAPPA were decreased in the patients who showed higher risks. Prenatal testing provides an advantage for early detection of this disorder.

Results of karyotype analysis and 22q11.2 (DiGeorge Syndrome critical region) deletion investigation in fetal cardiac system anomalies

The results of karyotype analysis and 22q11.2 ( DiGeorge Syndrome critical region) deletion investigation in fetal cardiac system anomalies &#x0D; Objective: We aimed to determine the presence of accompanying chromosomal anomalies and 22q11.2 deletion in patients with cardiac system anomalies.&#x0D; Material and Methods: In our retrospective and cross-sectional study, 99 fetuses born with cardiac anomalies were evaluated in terms of chromosomal anomalies. 36 fetuses were evaluated for 22q11.2 deletion. Fetuses who were diagnosed with prenatal congenital heart defect and underwent invasive prenatal diagnostic tests for fetal karyotyping between 01.01.2010 and 30.06.2017 at a tertiary cancer center were included in the study.&#x0D; Results: Of 99 cases, 48 (48.4%) had only cardiac anomalies and 51 (51.5%) had non-cardiac anomalies. Chromosomal anomalies were found in 37 (37.4%) of the cases. Autosomal trisomy 18(43.2%) and autosomal trisomy 21(32.4%) were the most common chromosomal anomalies. The study results support the strong association of chromosomal changes and cardiac malformation, especially in septal defects, atrioventricular septal defects, and conotruncal malformations. Deletion was detected in one(2.8%) of 36 cases evaluated for 22q11.2 deletion. The fetus with this deletion had isolated tetralogy of fallot and had no extracardiac anomaly.&#x0D; Conclusion: In cases with cardiac anomalies, isolated or accompanied by extracardiac anomalies, investigations should be made in terms of underlying chromosomal diseases in the perinatal evaluation. In addition, the investigation of 22q11.2 deletion in fetuses with conotruncal cardiac anomalies should be included in prenatal genetic examination.&#x0D; Keywords: DiGeorge Syndrome, Fetal Anomalies, karyotype, trisomy, 22q11.2 Deletion Syndrome

A case report on anaesthetic challenges in Patau syndrome: Navigating craniofacial and cardiac defects

The anaesthetic management of paediatric patients with Patau syndrome presents unique challenges, particularly when combined with craniofacial and cardiac defects and limited airway resources. This case report highlights our experience in managing a syndromic child with a difficult airway in a resource-constrained environment. The inability to secure the airway adequately can pose significant perioperative risks. In this case, we successfully utilized an oesophageal bougie as an alternative technique to secure the airway. This report emphasizes the importance of adapting to limited resources and employing innovative approaches to ensure optimal patient care in challenging situations.

The Predictive Value of Prenatal Cell-Free DNA Testing for Rare Autosomal Trisomies: A Systematic Review and Meta-analysis

ABSTRACT Noninvasive prenatal testing has been a reliable method for prenatal screening for the common autosomal trisomies for the last decade. It has been analyzed in many prospective studies for accuracy in screening for the most common trisomies—13, 18, and 21—and the technology has continued to progress. With high accuracy for common trisomies, advances are attempting to expand noninvasive prenatal testing for identifying rare autosomal trisomies, such as trisomies 7, 15, 16, and 22; sex chromosome aneuploidies; and segmental copy number variants. Although cell-free DNA (cfDNA) technology is now available to screen for these abnormalities, accuracy and detection rates have not been well studied. This systematic review analyzes and reports the diagnostic accuracy of cfDNA screening for the rare autosomal trisomies. This review included case series with 10 or more cases that reported on the accuracy of cfDNA in reporting rare autosomal trisomies that were confirmed by diagnostic results or postnatal genetic testing; the final review included 31 studies. Methodological analysis found the risk of bias to be high in most studies, with only 5 rated as high quality and low risk in all domains. All studies included in the final analyses were published between 2017 and 2022, and study populations ranged from 14 to 153,575 patients. Indications for screening and characteristics of the patients varied from study to study, with 12 studies in high-risk women, 10 studies in the general obstetric population, and 9 studies without inclusion of underlying risk factors and indications. Whole-genome sequencing was used in all studies as testing methodology. Testing timing varied and was performed anywhere from gestational week 8 to week 39. In the 3 studies that analyzed sensitivity and specificity of cfDNA testing, sensitivity ranged from 87.2% to 100%, and specificity ranged from 90.7% to 99.9%. In all 3 of these studies, there were significant limitations that led authors to acknowledge the difficulty of drawing clear conclusions about sensitivity and specificity from their data. Meta-analysis performed for positive predictive value (PPV) provided a pooled estimate of 11.46% (95% confidence interval [CI], 7.80%–15.65%). Sensitivity analysis including only studies at low risk of bias gave a PPV of 9.13% (95% CI, 2.49%–18.76%). Analysis was performed again with groups divided into high or low background risk, with a slightly higher PPV in the higher background risk group, but no significant difference between these groups (P = 0.595). Statistical heterogeneity was not explained by year of publication or baseline risk of participants but could be largely explained by rate of diagnostic follow-up. Studies with a follow-up rate of less than 50% showed a PPV of 23.69% (95% CI, 9.21%–41.94%), whereas studies with a follow-up rate greater than 50% reported a PPV of 8.80% (95% CI, 6.08%–11.90%). Based on the results of this systematic review and meta-analysis, it is likely that previously reported PPVs of cfDNA's diagnostic accuracy for detecting rare autosomal trisomies are overestimated. A reason for this could be lower follow-up rates as well as testing bias in women with high-risk cfDNA results. One reason for the low prevalence of rare autosomal trisomies is that many confirmed cases result in miscarriage before 12 weeks of gestation. Pregnancies that continue and that are not mosaic often experience major complications. The occurrence of mosaicism may impact the PPV, as mosaicism carries some risks but is sometimes not detected from cfDNA samples. This study was limited by the details included in the studies analyzed; this caused significant statistical heterogeneity, which limits the conclusions that can be drawn. In addition, detection rates may differ by type of cfDNA test, and this analysis did not stratify by type of test. The results of this analysis are consistent with previous literature on detection of rare autosomal trisomies in the general population and show that even with a high specificity and sensitivity for cfDNA testing in general, care should be taken in making clinical decisions on the part of both providers and patients in instances where a rare autosomal trisomy is suspected.