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Prenatal Diagnosis Jun 2024This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs).
METHODS
Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins.
RESULTS
In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins.
CONCLUSIONS
This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences.
Topics: Humans; Fetofetal Transfusion; Pregnancy; Fetal Growth Retardation; Female; Adaptation, Physiological; Heart Defects, Congenital; Twins, Monozygotic; Heart; Fetal Heart
PubMed: 38643403
DOI: 10.1002/pd.6575 -
Clinical Kidney Journal Apr 2024Immunoglobulin A nephropathy (IgAN) is characterized by diverse clinicopathological phenotypes. Herein we present a follow-up study of previously reported identical twin...
Immunoglobulin A nephropathy (IgAN) is characterized by diverse clinicopathological phenotypes. Herein we present a follow-up study of previously reported identical twin sisters with IgAN. The older sister exhibited more severe kidney histopathology and proteinuria and a lower birthweight than did her younger sister, and only the older sister experienced two childbirths. These raised concerns regarding her kidney outcomes. However, with timely multidisciplinary treatments, the older sister's kidney function remained preserved after 20 years of IgAN history. Our findings indicate the significant contribution of environmental/epigenetic factors to IgAN progression and the need for tailored medical care corresponding to life events.
PubMed: 38633839
DOI: 10.1093/ckj/sfae073 -
Frontiers in Cell and Developmental... 2024The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic...
The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins. DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using . Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents. We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially , , and . Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within , , , and . Causal inference indicated that the DNAm of 16 top CpGs within , , , , and might influence HGS, while HGS influenced DNAm at two CpGs within and . In validation analysis, methylation levels of six CpGs mapped to and one CpG mapped to were negatively associated with HGS weakness in community population. Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within and . These findings provide new clues to the epigenetic modification underlying muscle strength decline.
PubMed: 38633108
DOI: 10.3389/fcell.2024.1378680 -
Journal of Clinical Immunology Apr 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci. In the early 70s, complement deficiencies led to the description of familial forms of SLE caused by a single gene defect. High-throughput sequencing has recently identified an increasing number of monogenic defects associated with lupus, shaping the concept of monogenic lupus and enhancing our insights into immune tolerance mechanisms. Monogenic lupus (moSLE) should be suspected in patients with either early-onset lupus or syndromic lupus, in male, or in familial cases of lupus. This review discusses the genetic basis of monogenic SLE and proposes its classification based on disrupted pathways. These pathways include defects in the clearance of apoptotic cells or immune complexes, interferonopathies, JAK-STATopathies, TLRopathies, and T and B cell dysregulations.
Topics: Humans; Male; Antigen-Antibody Complex; Autoimmunity; Genome-Wide Association Study; Lupus Erythematosus, Systemic; Phenotype; Female; Twin Studies as Topic
PubMed: 38619739
DOI: 10.1007/s10875-024-01696-8 -
Consortium Psychiatricum Dec 2023We have described a clinical case of psychotic disorder induced by synthetic cathinones in one drug-addicted monozygotic twin. This clinical case is unique, because it...
We have described a clinical case of psychotic disorder induced by synthetic cathinones in one drug-addicted monozygotic twin. This clinical case is unique, because it offers the opportunity to observe many features of the singularity of the dependence syndrome in twin brothers: drug choice; motivation to use drugs; and the development of multiple, long-lasting psychoses in one of the brothers. We pursued a twelve-month follow-up of this case. The case substantiates the paucity of a fundamental understanding of mental disorders and highlights the importance of further research into the clinical features of drug-induced psychoses, especially those induced by novel psychoactive substances such as synthetic cathinones.
PubMed: 38618640
DOI: 10.17816/CP13619 -
Journal of Neurosurgery. Spine Apr 2024Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is... (Review)
Review
OBJECTIVE
Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members.
METHODS
This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included.
RESULTS
Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%).
CONCLUSIONS
Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.
PubMed: 38608294
DOI: 10.3171/2024.1.SPINE231277 -
ELife Apr 2024Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates...
Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4-82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.
Topics: Female; Pregnancy; Humans; Longevity; Fetus; Brain; Aging; Birth Weight
PubMed: 38602745
DOI: 10.7554/eLife.86812 -
Equine Veterinary Journal Jul 2024Twin gestation in the mare is undesirable and can have disastrous consequences. As in many cases, the key to success in twin management lies in a thorough follow-up and... (Review)
Review
Twin gestation in the mare is undesirable and can have disastrous consequences. As in many cases, the key to success in twin management lies in a thorough follow-up and accurate recording of clinical findings in the pre-breeding examination. A pregnancy diagnosis in the mobility phase is imperative for a good outcome in the event of twin reduction. If a twin gestation is not diagnosed during this early pregnancy stage, several other procedures exist for managing post-fixation twins (>16 days) with varying degrees of success. Most twin pregnancies are the result of multiple ovulations (dizygotic twins). However, monozygotic twins are also sporadically diagnosed, due to the increasing number of transferred in vitro produced equine embryos. In these cases, the most optimal treatment strategy still needs to be determined. This review provides an overview of the various twin reduction techniques described with the expected prognosis as well as of some less reported techniques with their results. In addition, physiological events and the reduction techniques are demonstrated to the user in virtual 3-dimensional illustrations.
Topics: Animals; Female; Pregnancy; Horse Diseases; Horses; Pregnancy Reduction, Multifetal; Pregnancy, Twin; Pregnancy, Animal
PubMed: 38594910
DOI: 10.1111/evj.14094 -
Advanced Materials (Deerfield Beach,... Jun 2024Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in...
Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in human embryo research, makes investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin embryos. In this study, a microthermoformed-based microwell screening platform is used to identify conditions that efficiently induce monochorionic twins in human stem cell-based blastocyst models, termed "twin blastoids". These twin blastoids contain a cystic GATA3+ trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, ready for implantation. This is functionally tested in a microfluidic chip-based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential. In conclusion, the development of technology enabling large-scale formation of twin blastoids, coupled with high-sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.
Topics: Humans; Female; Pregnancy; Twinning, Monozygotic; Blastocyst; Embryo, Mammalian; Chorion; Bioengineering; Models, Biological; Embryo Implantation
PubMed: 38593372
DOI: 10.1002/adma.202313306 -
Science Immunology Apr 2024Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the...
Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the contribution of these factors to immune system variability in tissues remains unexplored. The human uterus undergoes constant regeneration and is exposed to distinct environmental factors. To assess uterine immune system variation, we performed a system-level analysis of endometrial and peripheral blood immune cells in monozygotic twins. Although most immune cell phenotypes in peripheral blood showed high genetic heritability, more variation was found in endometrial immune cells, indicating a stronger influence by environmental factors. Cytomegalovirus infection was identified to influence peripheral blood immune cell variability but had limited effect on endometrial immune cells. Instead, hormonal contraception shaped the local endometrial milieu and immune cell composition with minor influence on the systemic immune system. These results highlight that the magnitude of human immune system variation and factors influencing it can be tissue specific.
Topics: Female; Humans; Twins, Dizygotic; Twins, Monozygotic; Endometrium; Uterus; Immune System
PubMed: 38579017
DOI: 10.1126/sciimmunol.adj7168