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Archives of Dermatological Research Jun 2024
Review
Topics: Humans; Hidradenitis Suppurativa; Trisomy 13 Syndrome
PubMed: 38935334
DOI: 10.1007/s00403-024-03196-6 -
Advances in Experimental Medicine and... 2024Tetralogy of Fallot (TOF) and double-outlet right ventricle (DORV) are conotruncal defects resulting from disturbances of the second heart field and the neural crest,... (Review)
Review
Tetralogy of Fallot (TOF) and double-outlet right ventricle (DORV) are conotruncal defects resulting from disturbances of the second heart field and the neural crest, which can occur as isolated malformations or as part of multiorgan syndromes. Their etiology is multifactorial and characterized by overlapping genetic causes. In this chapter, we present the different genetic alterations underlying the two diseases, which range from chromosomal abnormalities like aneuploidies and structural mutations to rare single nucleotide variations affecting distinct genes. For example, mutations in the cardiac transcription factors NKX2-5, GATA4, and HAND2 have been identified in isolated TOF cases, while mutations of TBX5 and 22q11 deletion, leading to haploinsufficiency of TBX1, cause Holt-Oram and DiGeorge syndrome, respectively. Moreover, genes involved in signaling pathways, laterality determination, and epigenetic mechanisms have also been found mutated in TOF and/or DORV patients. Finally, genome-wide association studies identified common single nucleotide polymorphisms associated with the risk for TOF.
Topics: Humans; Tetralogy of Fallot; Double Outlet Right Ventricle; Mutation; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Transcription Factors
PubMed: 38884738
DOI: 10.1007/978-3-031-44087-8_36 -
Advances in Experimental Medicine and... 2024Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and...
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.
Topics: Humans; Chromosome Aberrations; DNA Copy Number Variations; Genetic Predisposition to Disease; Heart Septal Defects, Ventricular; Mutation; Transcription Factors
PubMed: 38884729
DOI: 10.1007/978-3-031-44087-8_27 -
Cureus May 2024Trisomy 13, also known as Patau syndrome, is a widely congenital anomaly syndrome characterized by microphthalmia, cleft lip, and palate, microcephaly with a sloping...
Trisomy 13, also known as Patau syndrome, is a widely congenital anomaly syndrome characterized by microphthalmia, cleft lip, and palate, microcephaly with a sloping forehead, congenital heart disease, and polydactyly of the limbs. Patau syndrome is identified either prenatally or postnatally. Its survival rate is low, and most of the patients die even before their first year of life. The risk of trisomy 13 is higher in women of advanced maternal age. Brain and cardiovascular abnormalities are typically the primary factors contributing to the syndrome's poor prognosis. We report a case of a male newborn born at full term from a first-degree consanguineous marriage. Upon initial inspection, the patient had classic dysmorphic features, including low-set ears, a cleft lip and palate, a short neck, bilateral anophthalmia, and polydactyly of the limbs. After chromosomal analysis, the diagnosis was made, and a trisomy 13 was discovered.
PubMed: 38872687
DOI: 10.7759/cureus.60264 -
Autopsy & Case Reports 2024Trisomy 13, known as Patau syndrome, is a common aneuploidy with a well-known clinical phenotype. This case report describes a trisomy 13 patient with unusual autopsy...
Trisomy 13, known as Patau syndrome, is a common aneuploidy with a well-known clinical phenotype. This case report describes a trisomy 13 patient with unusual autopsy findings, including features resembling the Beckwith-Wiedemann Spectrum. Due to abnormalities of gestational ultrasounds, a prenatal karyotype of amniotic fluid cells was performed, which resulted in 47, XY+13. Autopsy microscopy studies identified leptomeningeal glioneuronal heterotopia, which was not described as belonging to Patau syndrome. Other atypical findings were diffuse hyperplasia of pancreatic islets of Langerhans and adrenals enlargement with marked adrenocortical cytomegaly, characteristically seen in the Beckwith-Wiedemann Spectrum. Molecular genetic tests were not performed for the Beckwith-Wiedemann Spectrum. Still, due to the rarity of both disorders, this report may support the evidence that trisomy 13 can affect tissue organization and lead to unusual histopathologic features resembling classic overgrowth disorders.
PubMed: 38770437
DOI: 10.4322/acr.2024.486 -
Taiwanese Journal of Obstetrics &... Mar 2024
Topics: Pregnancy; Female; Humans; Trisomy; Pregnant Women; Chromosome Disorders; Prenatal Diagnosis; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Aneuploidy
PubMed: 38485331
DOI: 10.1016/j.tjog.2024.01.030 -
Prenatal Diagnosis May 2024In singleton pregnancies, the use of cell-free DNA (cfDNA) analysis as a screening test for common fetal trisomies has spread worldwide though we still lack sufficient...
OBJECTIVE
In singleton pregnancies, the use of cell-free DNA (cfDNA) analysis as a screening test for common fetal trisomies has spread worldwide though we still lack sufficient data for its use in triplet pregnancies. The objective of this study is to assess the performance of cfDNA testing in detecting fetal aneuploidies in triplet pregnancies as a first-tier test.
METHOD
We performed a retrospective cohort study including data from pregnant women with a triplet pregnancy who underwent cfDNA testing between May 1, 2017, and January 15, 2020. cfDNA was obtained by massive parallel sequencing (VeriSeq NIPT solution; Illumina®). The objectives of the study were to assess the diagnostic performance of cfDNA testing for trisomy 21 (T21) (primary outcome), trisomy 18 (T18) and 13 (secondary outcomes).
RESULTS
During the study period, cfDNA testing was performed in 255 women with triplet pregnancy, of which 165 (64.7%) had a neonatal outcome available. Three tests were positive for T21, one of which was confirmed by an antenatal karyotype, and the other was confirmed at birth. The third case did not undergo an invasive procedure and was not confirmed at birth (false positive). In one case, cfDNA testing was positive for T18 and was confirmed by an antenatal karyotype. There were no cases of trisomy 13 in the cohort. The no-call rate was 2.4% at first sampling. Fifty-eight (22.7%) women had embryo reduction, which in 40 (69%) of whom was performed after the cfDNA test result.
CONCLUSION
cfDNA testing could be offered as primary screening for main fetal aneuploidies in triplet pregnancies after provision of appropriate patient information.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Cell-Free Nucleic Acids; Adult; Pregnancy, Triplet; Trisomy 18 Syndrome; Trisomy; Noninvasive Prenatal Testing; Trisomy 13 Syndrome; Cohort Studies; Down Syndrome; Maternal Serum Screening Tests; Prenatal Diagnosis
PubMed: 38448008
DOI: 10.1002/pd.6548 -
Mutation Research. Genetic Toxicology... 2024DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the...
DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990-2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed. Children examined were continuously eligible with ≥ 8 outpatient office visits during the 96-month period following birth. Among these children, 377 were diagnosed with FAS and 137,135 were not. The incidence rate of chromosomal anomalies involving segregation (trisomy 13, 18, or 21, n = 625), microdeletions (microdeletion syndromes, n = 39), and point mutations (sickle-cell anemia/cystic fibrosis, n = 2570) were examined using frequency risk ratio (RR) and logistic regression (adjusted odds ratio (aOR) for sex, race, residence, socioeconomic/environmental exposure status, and birth date) models. The incidence rates of chromosomal anomalies involving segregation (RR=5.92, aOR=5.85) and microdeletions (RR=41.6, aOR=34.1) were significantly increased in the FAS cohort as compared to the non-diagnosed cohort, but there was no difference in the incidence rate of point mutations (RR=1.14, aOR=1.29). Maternal toxicant exposure should be considered in the etiology of constitutional chromosomal anomaly in offspring.
Topics: Child; United States; Female; Pregnancy; Humans; Longitudinal Studies; Fetal Alcohol Spectrum Disorders; Cohort Studies; Chromosome Disorders; Chromosome Aberrations
PubMed: 38432776
DOI: 10.1016/j.mrgentox.2024.503737 -
BMC Medical Ethics Mar 2024The value of a short life characterized by disability has been hotly debated in the literature on fetal and neonatal outcomes. (Review)
Review
INTRODUCTION
The value of a short life characterized by disability has been hotly debated in the literature on fetal and neonatal outcomes.
METHODS
We conducted a scoping review to summarize the available empirical literature on the experiences of families in the context of trisomy 13 and 18 (T13/18) with subsequent thematic analysis of the 17 included articles.
FINDINGS
Themes constructed include (1) Pride as Resistance, (2) Negotiating Normalcy and (3) The Significance of Time.
INTERPRETATION
Our thematic analysis was guided by the moral experience framework conceived by Hunt and Carnevale (2011) in association with the VOICE (Views On Interdisciplinary Childhood Ethics) collaborative research group.
RELEVANCE
This article will be of interest and value to healthcare professionals and bioethicists who support families navigating the medically and ethically complex landscape of T13/18.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Child; Trisomy 13 Syndrome; Morals; Ethicists; Prenatal Care; Health Personnel
PubMed: 38431625
DOI: 10.1186/s12910-023-00994-x -
Nature Communications Feb 2024Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in...
Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice.
Topics: Pregnancy; Female; Humans; Down Syndrome; Trisomy; Trisomy 18 Syndrome; Chromosome Disorders; DNA, Ancient; Trisomy 13 Syndrome
PubMed: 38378781
DOI: 10.1038/s41467-024-45438-1