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Prenatal Diagnosis Dec 2022To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.
Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study).
OBJECTIVES
To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.
METHODS
Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed.
RESULTS
Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound.
CONCLUSIONS
NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.
Topics: Female; Humans; Pregnancy; Cell-Free Nucleic Acids; Cytogenetic Analysis; Predictive Value of Tests; Prenatal Diagnosis; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Italy
PubMed: 36403097
DOI: 10.1002/pd.6271 -
Cureus Oct 2022The cell-free fetal DNA (cffDNA) analysis for screening fetal genetic anomalies has increased dramatically since its commercialization in 2011 worldwide. In the early... (Review)
Review
The cell-free fetal DNA (cffDNA) analysis for screening fetal genetic anomalies has increased dramatically since its commercialization in 2011 worldwide. In the early weeks of pregnancy, it offers a hassle-free, non-invasive procedure of antenatal screening. It guides and protects mothers from undergoing unwanted risk-laden invasive prenatal testing. cffDNA testing is accurate at detecting the abnormal fetus chromosome among a large pool population. Patau syndrome, Edward syndrome, and Down syndrome are currently being accurately screened by this method. Due to their sensitivity and specificity, they now have become the screening method of choice, approaching almost 100% in various studies with a large sample pool. The latest procedures to analyze cffDNA, like the new digital droplet polymerase chain reaction (ddPCR) and sophisticated next-generation sequencing (NGS), have increased detection rates with decreased analyzing time. The latest techniques make it possible to screen large numbers of the population with faster report generation. Screening for Rh incompatibility and its timely prevention is now more accessible and more accurate with the help of cffDNA analysis. The problem arises when we deviate from the primary disease and start testing for anomalies not intended to be screened by cffDNA in the first place. Fetal sex chromosome aneuploidy screening by cffDNA is one area where the test gives mixed results either due to differences in machinery, laboratory parameters, or human error. Other rare occurrences like trisomes, such as trisomy 7, trisomy 16, trisomy 22, and a few microdeletion syndromes are also being screened but with less accuracy. Like every technology, cffDNA analysis is not entirely free of criticism. Its high testing cost, potential to accurately prognosticate the gender of the developing fetus and absence of standard testing practices will become an issue as the test becomes routine worldwide.
PubMed: 36381888
DOI: 10.7759/cureus.29965 -
Genes Nov 2022A vanishing twin (VT) occurs in up to 30% of early diagnosed twin pregnancies and is associated with an increased risk of fetal aneuploidy. Here, we describe our...
A vanishing twin (VT) occurs in up to 30% of early diagnosed twin pregnancies and is associated with an increased risk of fetal aneuploidy. Here, we describe our experience in a large VT population of 847 patients that underwent noninvasive prenatal testing (NIPT) for common fetal trisomies over a three-year period. All patients underwent an ultrasound examination prior to NIPT. Two comparison populations were included, namely, the singleton ( = 105,560) and the viable multiple gestation pregnancy samples ( = 9691) collected over the same period. All NIPT samples in the VT population received a result, of which 14 were high-risk for trisomy 21 (1.6%), nine for trisomy 18 (1.1%), and six for trisomy 13 (0.7%). Diagnostic testing confirmed the presence of trisomy 21 in 6/12 samples, giving a positive predictive value of 50%. One trisomy 18 case and no trisomy 13 cases were confirmed. The time between fetal demise and NIPT sampling did not appear to affect the number of true- or false-positive cases. In conclusion, NIPT is an effective screening method for trisomy 21 in the surviving fetus(es) in VT pregnancies. For trisomies 18 and 13, a positive NIPT should be interpreted carefully and ultrasound monitoring is preferrable over invasive diagnostic testing.
Topics: Pregnancy; Female; Humans; Trisomy; Down Syndrome; Trisomy 18 Syndrome; Noninvasive Prenatal Testing; Prenatal Diagnosis; Trisomy 13 Syndrome
PubMed: 36360264
DOI: 10.3390/genes13112027 -
The Journal of International Advanced... Nov 2022This study aimed to present the first cochlear implant surgery performed on a patient with Patau syndrome. In the auditory brainstem Response test performed on the 37th...
This study aimed to present the first cochlear implant surgery performed on a patient with Patau syndrome. In the auditory brainstem Response test performed on the 37th month, I-III-V waves at 100 dB were not obtained in the right ear, while I-III-V waves at 90 dB were obtained in the left ear. In the free-field audiometry test done in the first year, the threshold value of cochlear implantation was found to be 45 dB. While the Meaningful Auditory Integration Scale test result was 35/40, the Meaningful Use of Speech Scale test result was 13/40. The cochlear implantation was observed and found that hearing results are good and had a positive effect on the quality of life.
Topics: Child; Humans; Cochlear Implantation; Quality of Life; Trisomy 13 Syndrome; Cochlear Implants; Evoked Potentials, Auditory, Brain Stem; Speech Perception
PubMed: 36349678
DOI: 10.5152/iao.2022.20074 -
Prenatal Diagnosis Dec 2022Twins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal...
OBJECTIVE
Twins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twins. This study reports the performance of an SNP-based NIPT in the largest cohort with known outcomes for high-risk aneuploidy results.
METHOD
This is a retrospective analysis of 18,984 results from commercial single-nucleotide polymorphism (SNP)-based NIPT tests performed in twins between October 2, 2017 and December 31, 2019. Follow-up for all 211 high-risk cases was solicited.
RESULTS
Follow-up outcomes were obtained in 105 cases. Positive predictive values (PPVs) for high-risk results were 88.7% (63/71, 95% Confidence Interval [CI]: 79.0%-95.0%) for trisomy 21% and 72.7% (8/11, 95% CI: 39.0%-94.0%) for trisomy 18. The results were stratified into monozygotic (MZ) and dizygotic (DZ). The PPVs in MZ were 100% for both trisomy 21 (4/4, 95% CI: 40%-100%) and trisomy 18 (1/1, 95% CI: 2.5%-100%). No trisomy 13 cases were detected in the MZ group. The PPVs in DZ were 88.1% (59/67, 95% CI: 77.8%-94.7%), 70.0% (7/10, 95% CI: 34.8%-93.3%), and 66.7% (2/3, 95% CI: 9.4%-99.2%) for trisomy 21, trisomy 18, and trisomy 13, respectively.
CONCLUSION
The performance of SNP-based NIPT in this large twin cohort was comparable to previously reported twin NIPT studies. SNP-based NIPT allows for zygosity-based PPV assessment.
Topics: Female; Humans; Pregnancy; Aneuploidy; Down Syndrome; Noninvasive Prenatal Testing; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prenatal Diagnosis; Retrospective Studies; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Twins
PubMed: 36336878
DOI: 10.1002/pd.6262 -
Oman Medical Journal Sep 2022Individuals born with trisomy 13 tend to be susceptible to Meckel's diverticulum. It is rarely symptomatic and reported cases are extremely rare. We describe here a...
Individuals born with trisomy 13 tend to be susceptible to Meckel's diverticulum. It is rarely symptomatic and reported cases are extremely rare. We describe here a neonate with feeding intolerance and bilious aspirates as a result of Meckel's diverticulum and peritoneal band which caused intermittent volvulus with obstruction.
PubMed: 36188882
DOI: 10.5001/omj.2022.26 -
Annals of Medicine and Surgery (2012) Aug 2022and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of...
INTRODUCTION
and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of children die before reaching the age of six months.
CASE PRESENTATION
This report discusses a case of a male infant, two days old diagnosed with Patau syndrome. After birth, his APGAR score was satisfactory. The initial clinical examination revealed cleft palate, cleft lip, and congenital clubfoot. A pansystolic murmur was heard at the left sternal border. The patient was managed according and was referred to a surgeon for pulmonary binding, PDA ligation, VSD closure, and repair of ASA with disbanding of the pulmonary artery.
CLINICAL DISCUSSION
Studies have reported that patients with Patau syndrome present with cleft lip and palate, congenital heart defects, omphalocele, and holoprosencephaly. we also discovered dysmorphic characteristics such as the cleft palate and cleft lip, as well as serious congenital cardiac abnormalities. In addition, up to 80% of patients have been documented to have cardiac abnormalities, with patent ductus arteriosus, atrial septal defect, and ventricular septal defect.
CONCLUSION
Patau syndrome is the third most common trisomy found in infants. The clinical manifestation of Patau syndrome includes cleft palate, cleft lip, limb impairments, and congenital heart problems. Despite the fact that early diagnosis and management prognosis is poor for patients suffering from Patau syndrome. Genetic counseling may be beneficial not just for increasing awareness of the diagnosis and its implications.
PubMed: 36045789
DOI: 10.1016/j.amsu.2022.104100 -
European Journal of Human Genetics :... Dec 2022
Topics: Pregnancy; Female; Humans; Trisomy; Genetic Testing; Trisomy 13 Syndrome
PubMed: 36045223
DOI: 10.1038/s41431-022-01174-y -
The Malaysian Journal of Pathology Aug 2022Chromosomal abnormality is one of the causes of congenital disorders among newborns. Despite aneuploidy being the major cause of first trimester miscarriages, very few...
Chromosomal abnormality is one of the causes of congenital disorders among newborns. Despite aneuploidy being the major cause of first trimester miscarriages, very few aneuploidies such as trisomies of chromosomes 13, 18 and 21 survive to birth. The results of 4,064 patients referred for cytogenetic analysis at Human Genome Centre, Universiti Sains Malaysia, Kelantan, Malaysia between 2008 and 2019 were reviewed. We retrospectively investigated the karyotype patterns, clinical features and parental ages of the three common live-born autosomal trisomies such as trisomy 13, trisomy 18 and trisomy 21. The relative frequency of cases with the total sample received and cultured was calculated in each group and compared with those reported elsewhere. Between 2008 and 2019, a total of 1034 live-born trisomic cases which accounted for 25.4% of the 4064 total referred cases and 73.7% of 1403 suspected trisomy cases, were identified, with age ranging from newborns to 57 years. Down syndrome was the commonest aneuploidy (857 cases; 21.1%) followed by Edwards syndrome (133 cases; 3.3%) and Patau syndrome (44 cases; 1.1%). The number of diagnosed cases for each of the trisomies was fairly stable from year to year. About two-thirds of both maternal and paternal ages were ≥ 35 years. This is the first cytogenetic report on the common live-born autosomal trisomies in the North-Eastern region of Malaysia. The prevalence of trisomies 21 was found to be higher compared to an earlier study in the North-Western region of Malaysia, wherein also, advanced maternal age was a significant risk factor.
Topics: Adult; Aneuploidy; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; Down Syndrome; Female; Humans; Infant, Newborn; Karyotype; Malaysia; Parents; Retrospective Studies; Trisomy; Trisomy 13 Syndrome
PubMed: 36043586
DOI: No ID Found -
SAGE Open Medical Case Reports 2022Presentation, management, and outcomes of COVID-19 infections among younger patients is an area of medicine with deficits in research, likely due to the lower incidence...
Presentation, management, and outcomes of COVID-19 infections among younger patients is an area of medicine with deficits in research, likely due to the lower incidence of severe COVID-19 disease among the younger population. Management can be challenging, and clinicians often guide their decision-making based on the ever-changing protocols that are tailored mostly to the elderly population. Even more underrepresented in COVID-19 research are patients with chromosomal abnormalities and trisomy syndromes, as they appear less frequently, but have risk of increased morbidity and mortality due to underlying medical conditions. We describe a case of severe COVID-19 infection in a young patient with mosaic trisomy 13 and pre-existing polycystic kidney disease, who developed severe acute hypoxic respiratory failure and acute chronic kidney injury. The patient was provided maximal pharmacological support and her clinical course helps to shape the understanding of COVID-19 infections in the setting of chromosomal abnormalities and complex medical history.
PubMed: 36003892
DOI: 10.1177/2050313X221118732