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BMC Medical Genomics Feb 2018The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively...
Application of Neural Networks for classification of Patau, Edwards, Down, Turner and Klinefelter Syndrome based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics.
BACKGROUND
The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively over the past few years. The reason for this is that ANNs are good approximates of complex functions, so classification can be performed without the need for explicitly defined input-output model. This engineering tool can be applied for optimization of existing methods for disease/syndrome classification. Cytogenetic and molecular analyses are the most frequent tests used in prenatal diagnostic for the early detection of Turner, Klinefelter, Patau, Edwards and Down syndrome. These procedures can be lengthy, repetitive; and often employ invasive techniques so a robust automated method for classifying and reporting prenatal diagnostics would greatly help the clinicians with their routine work.
METHODS
The database consisted of data collected from 2500 pregnant woman that came to the Institute of Gynecology, Infertility and Perinatology "Mehmedbasic" for routine antenatal care between January 2000 and December 2016. During first trimester all women were subject to screening test where values of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (β-hCG) were measured. Also, fetal nuchal translucency thickness and the presence or absence of the nasal bone was observed using ultrasound.
RESULTS
The architectures of linear feedforward and feedback neural networks were investigated for various training data distributions and number of neurons in hidden layer. Feedback neural network architecture out performed feedforward neural network architecture in predictive ability for all five aneuploidy prenatal syndrome classes. Feedforward neural network with 15 neurons in hidden layer achieved classification sensitivity of 92.00%. Classification sensitivity of feedback (Elman's) neural network was 99.00%. Average accuracy of feedforward neural network was 89.6% and for feedback was 98.8%.
CONCLUSION
The results presented in this paper prove that an expert diagnostic system based on neural networks can be efficiently used for classification of five aneuploidy syndromes, covered with this study, based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics. Developed Expert System proved to be simple, robust, and powerful in properly classifying prenatal aneuploidy syndromes.
Topics: Adolescent; Adult; Computational Biology; Demography; Down Syndrome; Female; Humans; Klinefelter Syndrome; Male; Middle Aged; Mothers; Neural Networks, Computer; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Turner Syndrome; Ultrasonography; Young Adult
PubMed: 29439729
DOI: 10.1186/s12920-018-0333-2 -
International Journal of Molecular... Nov 2018Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so...
Patau Syndrome (PS), characterized as a lethal disease, allows less than 15% survival over the first year of life. Most deaths owe to brain and heart disorders, more so due to septal defects because of altered gene regulations. We ascertained the cytogenetic basis of PS first, followed by molecular analysis and docking studies. Thirty-seven PS cases were referred from the Department of Pediatrics, King Abdulaziz University Hospital to the Center of Excellence in Genomic Medicine Research, Jeddah during 2008 to 2018. Cytogenetic analyses were performed by standard G-band method and trisomy13 were found in all the PS cases. Studies have suggested that genes of chromosome 13 and other chromosomes are associated with PS. We, therefore, did molecular pathway analysis, gene interaction, and ontology studies to identify their associations. Genomic analysis revealed important chr13 genes such as FOXO1, Col4A1, HMGBB1, FLT1, EFNB2, EDNRB, GAS6, TNFSF1, STARD13, TRPC4, TUBA3C, and TUBA3D, and their regulatory partners on other chromosomes associated with cardiovascular disorders, atrial and ventricular septal defects. There is strong indication of involving FOXO1 (Forkhead Box O1) gene-a strong transcription factor present on chr13, interacting with many septal defects link genes. The study was extended using molecular docking to find a potential drug lead for overexpressed FOXO1 inhibition. The phenothiazine and trifluoperazine showed efficiency to inhibit overexpressed FOXO1 protein, and could be potential drugs for PS/trisomy13 after validation.
Topics: Chromosomes, Human, Pair 13; Cytogenetic Analysis; Female; Forkhead Box Protein O1; Heart Septal Defects; Humans; Karyotyping; Male; Molecular Docking Simulation; Protein Interaction Mapping; Trifluoperazine; Trisomy 13 Syndrome
PubMed: 30423812
DOI: 10.3390/ijms19113547 -
American Journal of Obstetrics and... Aug 2022Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a... (Observational Study)
Observational Study
BACKGROUND
Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy.
OBJECTIVE
To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed.
RESULTS
A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate.
CONCLUSION
In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.
Topics: Aneuploidy; Cell-Free Nucleic Acids; Chromosome Disorders; Down Syndrome; Female; Humans; Infant, Newborn; Nucleotides; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Prospective Studies; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 35085538
DOI: 10.1016/j.ajog.2022.01.019 -
The Eurasian Journal of Medicine Feb 2023Autosomal and sex chromosome aneuploidies are associated with multiple risk factors that determine their frequency and their social and health impact. We aimed to...
OBJECTIVE
Autosomal and sex chromosome aneuploidies are associated with multiple risk factors that determine their frequency and their social and health impact. We aimed to determine the clinical, phenotypic, and demographic characteristics of Peruvian children and neonates with autosomal and sex chromosome aneuploidies.
MATERIALS AND METHODS
This was a retrospective study conducted on 510 pediatric patients. We conducted a cytogenetic analysis with G-bands by trypsin using Giemsa (GTG) banding, and the results were reported using the International System for Cytogenetics Nomenclature 2013 system.
RESULTS
Of 399 children (mean age 2.1 ± 4 years), 84 (16.47%) had aneuploidies, with 86.90% being autosomal (73.81% trisomies). In autosomal aneuploidies, 67.85% (n = 57) of the children had Down syndrome where the most common cause was free trisomy 21 (52 cases, 61.91%), followed by Robertsonian translocation (4 cases, 4.76%). Edwards and Patau syndrome affected 4 (4.76%) and 1 (1.19%) neonate. The most frequent phenotypic characteristics in children with Down syndrome were Down syndrome-like facies (45.61%) and macroglossia (19.29%). Of sex chromosome aneuploidies, 6/7 were abnormalities of the X chromosome (mainly 45,X). Neonate's age (19 ± 44.9 months), paternal age (49 ± 9 years), height (93.4 ± 176 cm), and gestational age (30 ± 15.4 weeks) were significantly correlated with the presence of sex chromosome and autosomal aneuploidies (P < .001; P = .025; and P = .001).
CONCLUSIONS
Down syndrome and Turner's syndrome were the most frequent aneuploidy and sex chromosome aneuploidy, respectively. In addition, some of the clinical, phenotypic, and demographic characteristics, such as newborn's age, paternal age, gestational age, and height, were significantly correlated with the occurrence of aneuploidy. In this sense, these characteristics could be considered risk factors among this population.
PubMed: 36861858
DOI: 10.5152/eurasianjmed.2023.22070 -
Cureus Dec 2023The pathophysiology of Patau's syndrome involves the triplication of chromosomes, leading to multiple comorbidities. An omphalocele is characterized by a protrusion of...
The pathophysiology of Patau's syndrome involves the triplication of chromosomes, leading to multiple comorbidities. An omphalocele is characterized by a protrusion of abdominal contents from the base of the umbilical cord through the peritoneum. An omphalomesenteric duct remnant occurs when there is a failure of duct closure that results in a diverticulum extending from the fetal midgut to the yolk sac. While congenital defects rarely occur simultaneously in patients with Patau's syndrome, this case report describes a newborn with Patau syndrome who presented with both an omphalocele and an omphalomesenteric duct remnant. The newborn exhibited various congenital abnormalities such as coloboma, microphthalmia, broad nasal bridge, cleft lip, cleft palate, low-set ears, systolic murmur, omphalocele, intestinal umbilical fistula (omphalomesenteric continuous vitelointestinal duct remnant), polydactyly, rocker-bottom feet, left-sided clubbed foot, and ruptured myelomeningocele. Imaging revealed additional complications such as a large patent ductus arteriosus, hypoplastic distal arch, markedly dilated right atrium and left ventricle, and cerebellar hypoplasia. Chromosomal analysis confirmed the diagnosis of Patau's syndrome. Given the untreatable medical condition, the patient was placed under "Do Not Resuscitate," and palliative care was initiated. The simultaneous appearance of an omphalocele and an omphalomesenteric continuous vitelointestinal duct is rare, and surgical intervention is the standard of care if the patient is deemed suitable for surgery. However, in cases where surgery is not feasible, palliative care is initiated. Regardless of the outcome, genetic counseling is essential and should include a discussion on paternal autonomy, understanding the disorder, suggesting alternative management methods, and making crucial decisions concerning future family care and planning.
PubMed: 38125687
DOI: 10.7759/cureus.50793 -
Revista Brasileira de Ginecologia E... Jul 2018Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and/or placental hydrops. The disease...
Mirror syndrome is an unusual pathological condition in which maternal edema in pregnancy is seen in association with severe fetal and/or placental hydrops. The disease can be life-threatening for both the mother and the fetus. The pathogenesis is poorly understood, and may be confused with preeclampsia, even though distinguishing features can be identified. We report a rare case of mirror syndrome with maternal pulmonary edema associated with fetal hydrops due to Patau syndrome.
Topics: Adult; Edema; Female; Humans; Hydrops Fetalis; Pregnancy; Pregnancy Complications; Syndrome; Trisomy 13 Syndrome
PubMed: 29768639
DOI: 10.1055/s-0038-1653975 -
Archivos Peruanos de Cardiologia Y... 2021Most frequent chromosomal syndromes like Down, Patau, Edwards, Turner, and Williams affect the pediatric population in various ways, and congenital heart disease... (Review)
Review
Most frequent chromosomal syndromes like Down, Patau, Edwards, Turner, and Williams affect the pediatric population in various ways, and congenital heart disease explains the altered quality of life they suffer. There is a lack of studies reviewing the cardiac anomalies in these syndromes, and the ones that exist are publications from past decades. We reviewed databases such as MEDLINE, LILACS, SCIELO, and Google Scholar, selecting the best possible evidence, and each chromosomal syndrome was investigated in relation to congenital heart disease, constituting five search groups. The article shows the characteristics of each heart disease described in the studies reviewed, the author, date of publication, country, and population studied, as well as a brief description of the frequency of the disease and its mortality. The results described in this review were contrasted with previous existing literature to verify if there was correspondence between the reported frequencies. The most frequent congenital heart diseases were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), atrial septal defect (ASD), and persistent ductus arteriosus (PDA) in Down syndrome patients, PDA, ASD, and VSD in Patau syndrome patients, AVSD, PDA and valvular defects in Edwards syndrome, bicuspid aortic valve, aortic coarctation and aortic stenosis in Turner syndrome, and supravalvular aortic stenosis and pulmonary stenosis in Williams syndrome.
PubMed: 37727523
DOI: 10.47487/apcyccv.v2i3.155 -
Journal of Clinical Medicine Mar 2022Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter... (Review)
Review
Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter abnormalities, and intellectual disabilities. Trisomies are generated by an error of chromosomal segregation during cell division. Accumulating evidence has shown that deregulated gene expression resulting from the triplication of chromosomes 13 and 18 is associated with many disturbed cellular processes. Moreover, a disturbed oxidative stress status may be implicated in the occurrence of fetal malformations. Therefore, a literature review was undertaken to provide novel insights into the evaluation of trisomy 13 (T13) and 18 (T18) pathogeneses, with a particular concern on the oxidative stress. Corresponding to the limited literature data focused on factors leading to T13 and T18 phenotype occurrence, the importance of oxidative stress evaluation in T13 and T18 could enable the determination of subsequent disturbed metabolic pathways, highlighting the related role of mitochondrial dysfunction or epigenetics. This review illustrates up-to-date T13 and T18 research and discusses the strengths, limitations, and possible directions for future studies. The progressive unification of trisomy-related research protocols might provide potential medical targets in the future along with the implementation of the foundation of modern prenatal medicine.
PubMed: 35407395
DOI: 10.3390/jcm11071787 -
Autopsy & Case Reports 2013Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early...
Holoprosencephaly (HPE) is a congenital defect of the brain, median structures, and face resulting from an incomplete cleavage of the primitive brain during early embryogenesis. The authors report a case of trisomy 13 syndrome diagnosed at prenatal follow up. The preterm newborn lived only 5 hours, and died because of severe respiratory failure. The autopsy findings disclosed facial, skull, limbs, cardiac, and cerebral malformations. Among the latter, the presence of alobar HPE, the central theme of this report, was evident. The most common nonrandom chromosomal abnormality in patients with HPE is trisomy 13. The most severe variant, namely alobar HPE, is shown in this case report. Discussion on this severe anomaly, along with the case report with details of Patau's syndrome, is the goal of this report.
PubMed: 31528602
DOI: 10.4322/acr.2013.012 -
Revista Paulista de Pediatria : Orgao... Dec 2013To describe gestational, perinatal and family findings of patients with Patau syndrome (PS).
OBJECTIVE
To describe gestational, perinatal and family findings of patients with Patau syndrome (PS).
METHODS
The study enrolled patients with PS consecutively evaluated during 38 years in a Clinical Genetics Service of a pediatric referral hospital in Southern Brazil. The clinical data and the results of cytogenetic analysis were collected from the medical records. For statistical analysis, the two-tailed Fisher's exact test and the chi-square test with Yates' correction were used, being significant p<0.05.
RESULTS
The sample was composed of 27 patients, 63% were male, with a median age of nine days at the first evaluation. Full trisomy of chromosome 13 was the main cytogenetic finding (74%). Only six patients were submitted to obstetric ultrasound and none had prenatal diagnosis of PS. The patients' demographic characteristics, compared to born alive infants in the same Brazilian state showed a higher frequency of: mothers with 35 years old or more (37.5%); multiparous mothers (92.6%); vaginal delivery (77%); preterm birth (34.6%); birth weight <2500g (33.3%), and Apgar scores <7 in the 1st (75%) and in the 5th minute (42.9%). About half of them (53%) died during the first month of life.
CONCLUSIONS
The understanding of the PS patients' gestational, perinatal and family findings has important implications, especially on the decision about the actions to be taken in relation to the management of these patients.
Topics: Chromosome Disorders; Chromosomes, Human, Pair 13; Female; Humans; Infant; Infant, Newborn; Male; Pregnancy; Retrospective Studies; Trisomy; Trisomy 13 Syndrome
PubMed: 24473950
DOI: 10.1590/S0103-05822013000400007