Monozygotic Monochorionic Twins Research Articles

Cellular mechanisms of monozygotic twinning: clues from assisted reproduction.

Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts. However, there are a growing number of ART cases where a single blastocyst transfer results in dichorionic MZ twins, indicating that embryo splitting may occur even after blastocyst formation. For monochorionic MZ twins, we conducted a comprehensive analysis of the cellular mechanisms involved in ICM splitting, drawing from both ART cases and animal experiments. In addition, we critically re-examine the classic early splitting model for dichorionic MZ twins. We explore cellular mechanisms leading to two separated blastocysts in ART, potentially causing dichorionic MZ twins. Relevant studies including research articles, reviews, and conference papers were searched in the PubMed database. Cases of MZ twins from IVF clinics were found by using combinations of terms including 'monozygotic twins' with 'IVF case report', 'ART', 'single embryo transfer', or 'dichorionic'. The papers retrieved were categorized based on the implicated mechanisms or as those with unexplained mechanisms. Animal experiments relating to MZ twins were found using 'mouse embryo monozygotic twins', 'mouse 8-shaped hatching', 'zebrafish janus mutant', and 'nine-banded armadillo embryo', along with literature collected through day-to-day reading. The search was limited to articles in English, with no restrictions on publication date or species. For monochorionic MZ twins, ART cases and mouse experiments demonstrate evidence that a looser ICM in blastocysts has an increased chance of ICM separation. Physical forces facilitated by blastocoel formation or 8-shaped hatching are exerted on the ICM, resulting in monochorionic MZ twins. For dichorionic MZ twins, the classic model resembles artificial cloning of mouse embryos in vitro, requiring strictly controlled splitting forces, re-joining prevention, and proper aggregation, which allows the formation of two separate human blastocysts under physiological circumstances. In contrast, ART procedures involving the transfer of a single blastocysts after atypical hatching or vitrified-warmed cycles might lead to blastocyst separation. Differences in morphology, molecular mechanisms, and timing across various animal model systems for MZ twinning can impede this research field. As discussed in future directions, recent developments of innovative in vitro models of human embryos may offer promising avenues for providing fundamental novel insights into the cellular mechanisms of MZ twinning during human embryogenesis. Twin pregnancies pose high risks to both the fetuses and the mother. While single embryo transfer is commonly employed to prevent dizygotic twin pregnancies in ART, it cannot prevent the occurrence of MZ twins. Drawing from our understanding of the cellular mechanisms underlying monochorionic and dichorionic MZ twinning, along with insights into the genetic mechanisms, could enable improved prediction, prevention, and even intervention strategies during ART procedures. N/A.

Management of twin reversed arterial perfusion sequence: eight cases over 13 years.

Twin reversed arterial perfusion (TRAP) sequence is a rare condition that affects primarily monozygotic monochorionic twin pregnancies in which a normal twin acts as a pump (donor) for an acardiac recipient (perfuse) twin. We report our experience over the last 13 years at a tertiary health care center. Descriptive, retrospective case series SETTING: Tertiary health care center PATIENTS AND METHODS: All TRAP cases managed between the years 2009 and 2022 at our Fetal Diagnosis and Therapy Center were included. Data recorded included demographic and clinical information which was used to generate descriptive data. Patients were managed by a multidisciplinary team with variable interventions. Survival of normal twin SAMPLE SIZE: Eight RESULTS: Eight pregnant women with TRAP syndrome were managed at our center during that period. One was monozygotic monochorionic and the others were monochorionic diamniotic. Median maternal age at presentation was 27 years and median gestational age at diagnosis was 23 weeks. All were diagnosed with ultrasound (US) imaging. Three were managed with bipolar ligation of the cord of the acardiac twin under general anesthesia, one US-guided (single port) and 2 fetoscopic (2 ports) with a median operative time of 39 minutes. The last five cases were managed with US-guided radiofrequency ablation (RFA) under local anesthesia, one needed 2 sessions, 1 week apart. The median duration of the RFA procedure was 23 minutes. There were no complications and all had viable normal babies born at a median of 32 weeks of gestation (6 C-section, 2 spontaneous membrane rupture). Acardiac twin cord ligation and RFA are feasible and safe options with excellent outcome for TRAP syndrome. RFA may be preferable owing to its less invasiveness under local anesthesia. None, given the rarity of the disease and the study design. None.

Early-life residential green spaces and traffic exposure in association with young adult body composition: a longitudinal birth cohort study of twins

BackgroundGlobally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins.MethodsAs part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested.ResultsEach interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2–2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4–1.3%), 1.4% increase in waist circumference (95%CI 0.5–2.2%), and 2.3% increase in body fat (95%CI 0.2–4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5–2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6–2.2%).ConclusionsThe built environment in which mothers reside during pregnancy might play a role on body composition among young adult twins. Our study revealed that based on zygosity/chorionicity type differential effects of prenatal exposure to green spaces on body composition at adult age might exist.

Prenatal adverse environment is associated with epigenetic age deceleration at birth and hypomethylation at the hypoxia-responsive EP300 gene

BackgroundObstetric complications have long been retrospectively associated with a wide range of short- and long-term health consequences, including neurodevelopmental alterations such as those observed in schizophrenia and other psychiatric disorders. However, prospective studies assessing fetal well-being during pregnancy tend to focus on perinatal complications as the final outcome of interest, while there is a scarcity of postnatal follow-up studies. In this study, the cerebroplacental ratio (CPR), a hemodynamic parameter reflecting fetal adaptation to hypoxic conditions, was analyzed in a sample of monozygotic monochorionic twins (60 subjects), part of them with prenatal complications, with regard to (i) epigenetic age acceleration, and (ii) DNA methylation at genes included in the polygenic risk score (PRS) for schizophrenia, and highly expressed in placental tissue.ResultsDecreased CPR measured during the third trimester was associated with epigenetic age deceleration (β = 0.21, t = 3.362, p = 0.002). Exploration of DNA methylation at placentally expressed genes of the PRS for schizophrenia revealed methylation at cg06793497 (EP300 gene) to be associated with CPR (β = 0.021, t = 4.385; p = 0.00008, FDR-adjusted p = 0.11). This association was reinforced by means of an intrapair analysis in monozygotic twins discordant for prenatal suffering (β = 0.027, t = 3.924, p = 0.001).ConclusionsPrenatal adverse environment during the third trimester of pregnancy is associated with both (i) developmental immaturity in terms of epigenetic age, and (ii) decreased CpG-specific methylation in a gene involved in hypoxia response and schizophrenia genetic liability.

Hétérotopie gliale pulmonaire : une lésion exceptionnelle chez un nourrisson avec un jumeau anencéphale

Pulmonary glial heterotopia is an extremely rare entity whose pathophysiology remains unclear. We report for the first time one case of pulmonary glial heterotopia occured in a one-month baby free from any malformation. She has the particularity of being born from monozygotic monochorionic twin pregnancy where her anencephalic exencephalic sister suffered a medical termination of pregnancy. She presented neonatal respiratory distress, which recurred one month later. Chest X-ray revealed bilateral cystic pulmonary lesions mainly located in the right lung. Given the suspicion of congenital cystic adenomatoid malformation (CCAM), she underwent an upper and a lower right lung lobectomy at four months old. The pathological study found a multi-cystic lesion consisted of well-differentiated and poorly cellular glial tissue sometimes lined by bronchic epithelium. There was no pathological evidence for a CCAM. The evolution was favorable after surgery with an infant who was well five months later. This is one of the very few cases where the disease did not lead to rapid death in utero or during the perinatal period. This suggests that effective management by surgery could be a decisive factor in the survival of these patients.

Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction.

BackgroundIntrauterine growth restriction (IUGR), which refers to reduced fetal growth in the context of placental insufficiency, is etiologically heterogeneous. IUGR is associated not only with perinatal morbidity and mortality but also with adult-onset disorders, such as cardiovascular disease and diabetes, posing a major health burden. Placental epigenetic dysregulation has been proposed as one mechanism that causes IUGR; however, the spectrum of epigenetic pathophysiological mechanisms leading to IUGR remains to be elucidated. Monozygotic monochorionic twins are particularly affected by IUGR, in the setting of severe discordant growth. Because monozygotic twins have the same genotype at conception and a shared maternal environment, they provide an ideal model system for studying epigenetic dysregulation of the placenta.ResultsWe compared genome-wide placental DNA methylation patterns of severely growth-discordant twins to identify novel candidate genes for IUGR. Snap-frozen placental samples for eight severely growth-discordant monozygotic monochorionic twin pairs were obtained at delivery from each twin. A high-resolution DNA methylation array platform was used to identify methylation differences between IUGR and normal twins. Our analysis revealed differentially methylated regions in the promoters of eight genes: DECR1, ZNF300, DNAJA4, CCL28, LEPR, HSPA1A/L, GSTO1, and GNE. The largest methylation differences between the two groups were in the promoters of DECR1 and ZNF300. The significance of these group differences was independently validated by bisulfite pyrosequencing, implicating aberrations in fatty acid beta oxidation and transcriptional regulation, respectively. Further analysis of the array data identified methylation changes most prominently affecting the Wnt and cadherin pathways in the IUGR cohort.ConclusionsOur results suggest that IUGR in monozygotic twins is associated with impairments in lipid metabolism and transcriptional regulation as well as cadherin and Wnt signaling. We show that monozygotic monochorionic twins discordant for growth provide a useful model to study one type of the epigenetic placental dysregulation that drives IUGR.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0238-x) contains supplementary material, which is available to authorized users.

The Influence of Chorion Type on Health Measures at Birth and Dental Development in Australian and Dutch Twins: A Comparative Study.

Chorion type may significantly influence the prenatal environment of twins. This study explored the associations between chorion type and gestational age, birth weight, birth length, and the timing of emergence of the first primary tooth in two populations of twins, Australian and Dutch. Additionally, we investigated the relationship between chorion type and birth weight discordance (BWD) in order to determine whether a significant relationship existed between discordance in birth weight and discordance in the timing of emergence of the first primary tooth. The two study samples consisted of 409 Australian twin pairs and 301 Dutch twin pairs, all of European ancestry. Data were collected through a combination of questionnaires and recording charts administered to the parents and through linkage with biological databases. In the Australian sample, monozygotic monochorionic (MZMC) twins experienced the shortest mean gestation time (35 weeks), the lowest mean birth length (46 cm) and the lowest mean birth weight (2.3 kg) compared with other twin groups. For the same variables in the Dutch sample, these trends with MZMC twinning were not observed. Chorion type did not significantly affect the mean timing of emergence of the first primary tooth in either sample. Monochorionicity was found to be significantly associated with BWD in both samples, but there was a significant association between BWD in MZMC twin pairs and timing of emergence of the first primary tooth only in the Australian sample. Results from this study support previous findings that the timing of emergence of the first primary tooth is influenced strongly by genetic factors and is well protected from environmental disturbances.

What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization

To identify the incidence, risk factors, and obstetric/perinatal outcomes associated with monozygotic twins (MZTs) after IVF. Nested case-control. University-based center. The IVF cycles eventuating in pregnancy from 2000-2009. None. The MZT incidence, chorionicity/zygosity, pregnancy/neonatal outcome. Of 6,223 gestations, 131 MZTs were diagnosed (2.1% incidence; 2.0% in autologous and 2.7% in donor IVF cycles), 10 were dichorionic, and 121 were monochorionic. Controlling for all risk factors, young oocyte age, extended culture (noncleavage embryos transferred on/after day 4), and year of IVF treatment cycle were significantly associated with MZT. When assessing factors associated with specific MZT placentation, day 3 assisted hatching correlated more with dichorionic MZT, whereas extended culture and advanced day 5 embryonic stage correlated with monochorionic MZT. Comparing monozygotic to dizygotic multigestation outcomes, MZT fared worse; however, once controlling for triplet gestation, only gestational age at delivery remained significantly compromised in the monozygotic group. After IVF the incidence of MZT is high, with young oocyte age, year of treatment, and extended culture (or embryo stage at transfer) conferring greatest risk. Regarding MZT type, assisted reproductive technology (ART) procedures may influence the timing of embryonic splitting (i.e., division in early embryonic development may be influenced by zona pellucida [ZP] manipulation whereas later splitting may occur during delayed implantation). Poor obstetric/perinatal outcome is significantly impacted by the presence of an "extra" fetus, as high-order multiple gestation concurrent with an MZT conveyed the worst prognosis.

Twin-to-Twin Transfusion Syndrome

TTTS is a specific condition that only occurs in multiple pregnancies of monozygotic (monochorionic) twins. When twins share a single placenta, the blood vessels become mutually interconnected in the placenta, so that blood flows back and forth between both twins. DOI: http://dx.doi.org/10.3126/jnps.v33i2.8379 J Nepal Paediatr Soc. 2013; 33(2):157

Report of Neuroblastoma in a Set of Monozygotic Monochorionic Twins

Report of Neuroblastoma in a Set of Monozygotic Monochorionic Twins

Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

BackgroundLow birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes.ResultsOverall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences.ConclusionsSevere intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.

Fetal Diagnosis of Left-Ventricular Noncompaction Cardiomyopathy in Identical Twins With Discordant Congenital Heart Disease

Left-ventricular noncompaction (LVNC) is characterized by prominent myocardial trabeculae with deep intratrabecular recesses. Associated with ventricular dysfunction, LVNC can present in isolation or in conjunction with structural heart defects (i.e., "nonisolated" LVNC). Although it was once considered to be difficult and unreliable, successful detection of this condition by way of fetal echocardiography has been well documented. We present what is to our knowledge the first prenatal diagnosis of LVNC in monochorionic-monozygotic twins. Nonisolated LVNC was identified in twins A and B at 23 weeks' gestation. A noncompaction-to-compaction ratio >2 was documented in both cases. Discordance for congenital heart disease was observed in the twins: Twin A presented with pulmonary atresia with an intact ventricular septum, critical tricuspid stenosis, and severe right-ventricular hypoplasia, whereas twin B presented with mild mitral valve dysplasia. Despite an initially complicated postnatal course for twin A, this case shows that it is feasible to achieve good outcomes with accurate prenatal detection and aggressive postnatal management.

Pre-natal, clonal origin of t(1;11)(p32;q23) acute lymphoblastic leukemia in monozygotic twins

Aim Observation of identical genetic changes in leukemia cells from monozygotic twin pairs has provided evidence for the in utero single clonal origin hypothesis of leukemia, with intraplacental metastasis the basis for concordance. Investigation of this rare mixed lineage leukemia ( MLL) cytogenetic abnormality aims to provide further evidence of the genetic changes that underpin this aggressive form of leukemia in infants. Method The clinical features of a monozygotic infant twin pair with acute lymphoblastic leukemia (ALL) are reported. Banded chromosomal analysis and fluorescent in situ hybridization were used for cytogenetic characterization of the leukemic cells. Immunophenotype was determined by flow cytometry and polymerase chain reaction was used to determine the presence of FLT3-D835/I836 and FLT3-internal tandem duplication (ITD) mutations. Results The twins were seven weeks of age at diagnosis. Both had cytogenetic evidence for the t(1;11)(p32;q23) translocation. Trisomy X was present in a subpopulation of cells in one twin. Immunophenotypic profile at diagnosis was consistent with B precursor ALL (CD19, CD24, CD33 positive, weak CD13 positivity, CD10 negative) and both were negative for FLT3-D835/I836 and FLT3-ITD mutations. Conclusions This is the first report of monochorionic monozygotic twins harboring the t(1;11)(p32;q23) translocation. Identification of this rare translocation in both twins, indicates a common stem line and provides further evidence for the intrauterine monoclonal origin for infant ALL with concordance explained by the shared circulation. Genetic diversity was observed in a subpopulation of cells from one twin at diagnosis. We must now utilize the sophisticated molecular biology tools available to capture changes at the genome-wide level to gain further insight into the complex events contributing to MLL leukemogenesis in infants.

The Influence of Genetic and Environmental Factors on the Etiology of the Human Umbilical Cord: The East Flanders Prospective Twin Survey1

The umbilical cord is vulnerable to a number of insults that may alter cord morphology, diminish cord flow, and ultimately compromise fetal nutrition. Thus, an investigation of the underlying mechanisms of the development of cord morphology and possible pathologies associated with it may provide insight regarding fetal growth in the intrauterine environment and have an impact on later development of the child. To our knowledge, this study, which included 11,980 twins, is the first to report the relative contribution of genes and environment in the development of the cord. Umbilical cord length, insertion, knots, twisting, and number of vessels were examined by trained midwives at birth. Means and percentages of cord characteristics by twin zygosity/chorionicity and gender were calculated. ANOVA and chi-square tests were performed to calculate discordance in cord morphology between dizygotic (DZ), monozygotic monochorionic (MZMC), and monozygotic dichorionic (MZDC) twins. Univariate genetic models were fit to the umbilical cord characteristics to investigate the genetic and environmental influences on umbilical cord morphology. Mainly nonshared environmental but also genetic factors influence umbilical cord morphology. In MZMC male and female twins, a peripheral/marginal cord insertion was significantly (P < 0.01) more prevalent compared to MZDC and DZ male and female twins, respectively. In MZMC male twins, clockwise twisting was significantly (P = 0.02) less frequent compared to DZ twins. Environmental and genetic factors influence cord morphology and pathology. Twin members can experience environmental influences that are not shared between them even in that very early stage of in utero life.

Discordant Blood Chimerism in Dizygotic Monochorionic Laser-Treated Twin–Twin Transfusion Syndrome

Twin-twin transfusion syndrome occurs in 10% of monozygotic monochorionic twin gestations and results from an unbalanced exchange of blood from the donor to the recipient fetus through placental anastomoses. We present a case of twin-twin transfusion syndrome with differing fetal sex treated with in utero laser surgery. Genetic analyses showed 46,XX/46,XY hematologic chimerism in both twins at birth and at 6 months, with the recipient twin being significantly more chimeric than the donor. Placental pathologic examination confirmed monochorionicity and laser ablation of all anastomoses. Despite in utero separation of the fetal circulations remote from delivery, hematologic chimerism persisted after birth. We speculate that the greater degree of blood chimerism in the recipient compared with the donor was related to the pathophysiology of twin-twin transfusion syndrome before laser surgery.

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome

Beckwith–Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood-specific hypomethylation phenotype most probably caused by a feto-fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.

Difference in nuchal translucency between monozygotic and dizygotic spontaneously conceived twins

To assess nuchal translucency (NT) thickness and differences in inter-twin NT thickness among naturally conceived monozygotic and dizygotic twins. Enrolled women prospectively underwent NT measurement for both twins between 11 and 14 weeks of gestational age. NT thickness and inter-twin NT difference were recorded and compared among dizygotic twins, monozygotic dichorionic twins, and monozygotic monochorionic twins. This study obtained analyzable data for 174 monozygotic twins and 107 dizygotic twins. Of the 174 monozygotic twins, 105 were monochorionic, and 69 were dichorionic. Monozygotic monochorionic twin pregnancies had a significantly higher mean fetal NT thickness (1.48 +/- 0.62 mm) than either dizygotic twin pregnancies (1.34 +/- 0.50 mm) or monozygotic dichorionic twin pregnancies (1.31 +/- 0.48 mm). Mean inter-twin NT difference was significantly lower in monozygotic dichorionic twin pregnancies (0.37 +/- 0.19 mm) than in dizygotic twin pregnancies (0.57 +/- 0.22 mm) or monochorionic twin pregnancies (0.65 +/- 0.43 mm).Irrespective of twin zygosity, NT thickness and inter-twin NT difference were larger in monochorionic twins than in dichorionic twins (1.48 +/- 0.62 mm versus 1.33 +/- 0.49 mm, and 0.65 +/- 0.43 mm versus 0.49 +/- 0.23 mm, respectively). During first-trimester ultrasonographic screening for Down syndrome, monochorionic twin pregnancies have the greatest NT thickness and monozygotic dichorionic twin pregnancies have the lowest inter-twin NT difference.

Case series: TRAP sequence

TRAP (twin reversed arterial perfusion) sequence / acardiac twinning is a rare anomaly that occurs in monozygotic monochorionic twins with an incidence of 1% and in 1 in 35,000 pregnancies overall. The anomalous twin appears as a heterogeneous mass, simulating a teratoma or intrauterine fetal demise. As the normal twin faces increased morbidity and mortality, antenatal diagnosis with gray-scale examination, and Doppler confirmation of the diagnosis of TRAP sequence in twin pregnancies, aids in proper prenatal management. We report two cases of TRAP sequence that we encountered over a single month, with the two cases having different outcomes.

PLACENTAL PATHOLOGY IN TRAP SEQUENCE: CLINICAL AND PATHOGENETIC IMPLICATIONS

Twin reversed arterial perfusion sequence (TRAP) resulting in an acardiac twin is a rare occurrence. Acardia requires the presence of arterial-arterial anastomosis, with retrograde perfusion of poorly oxygenated blood from the normal twin to the acardiac twin, venous-venous anastomosis carrying blood back from the acardiac to the normal twin, and circulatory failure of the acardiac twin. Although vascular anastomoses in cases of TRAP have been well described, there is little published literature on the microscopic changes in the placenta in TRAP sequence. We report a case of monochorionic monozygotic twins with an acardiac twin, large arterial-arterial anastomosis, and direct continuity of the umbilical cord veins. The placenta showed villous immaturity, striking villous calcifications, and extensive fetal thrombotic vasculopathy of the umbilical vein of the donor twin and the chorionic plate vessels. Thrombi in the umbilical vessels of the acardiac twin have been reported, and trombi in donor twin organs have been seen after fetal demise in utero. But to our knowledge there is no previously reported thrombi in the donor twin umbilical vessels or the chorionic plate veins. This may have implications not only as a possible factor in the etiology of TRAP, but also and more important as a possible risk factor for thrombotic events in the donor twin. Further studies with clinico-pathological correlation are needed to explore this issue.

Acardiac Twin Presenting as Fetus Amorphous with an Attenuated Umbilical Cord

Acardiac anomaly sequence is a rare malformation cluster occurring in the setting of monozygotic monochorionic twin pregnancies. In addition to an absent heart (acardia), variable degrees of somatic developmental disruption are present. We describe an extreme example of what we believe to be acardiac twinning, with almost complete absence of gross tissue organization but recognizable microscopic evidence of body-axis establishment and organ formation. The case is also notable for the absence of a grossly identifiable umbilical cord, with attachment to the placental vasculature by 2 vessels invested by amnion but without Wharton's jelly. We discuss the controversy regarding the requirement of an umbilical cord in the definition of acardiac twin and distinguish this case from placental teratoma.