Search

We report a 32-year-old G3P1 at 35 weeks 3 days with a dichorionic, diamniotic twin gestation who presented for evaluation secondary to ventriculomegaly (VM) in one twin. Fetal ultrasound and MRI demonstrated microcephaly, severe VM, compression of the corpus callosum, scalp and nuchal thickening, elongated ears, bilateral talipes, right-sided congenital diaphragmatic hernia (CDH), and loss of normal cerebral architecture, indicative of a prior insult in the affected twin. The co-twin was grossly normal. The family pursued a palliative care pathway for the affected twin and was delivered at 37 weeks and 6 days. The affected twin passed away within the first hour of life due to respiratory compromise. Postmortem trio exome sequencing identified a homozygous likely pathogenic variant in ATP1A2 (c.2439+1G>A). Although this variant is novel, it is predicted to affect the donor split site in intron 17, resulting in a frameshift and complete loss-of-function of the gene. Biallelic loss of function variants in this gene have been reported in seven individuals with multiple anomalies similar to those in the affected twin. However, only one other individual with a possible CDH has been previously reported. Our case suggests that CDH be included in the phenotypic spectrum of this disorder and reports the first frameshift mutation causing this autosomal recessive multiple congenital anomaly syndrome., (© 2024 John Wiley & Sons Ltd.)

Introduction: Pitt-Hopkins syndrome (PTHS) is a rare genetic syndrome associated with neurodevelopmental disorders and craniofacial dysmorphisms caused by variations in the TCF4 transition factor. The aim of this article was to report the case of two twin infants diagnosed with PTHS, confirmed by the identification of a heterozygous pathogenic variant in the TCF4 gene through DNA extracted from a buccal swab., Case Presentation: Both infants presented with craniofacial asymmetry with a metopic crest and cranial deformity. During the diagnostic investigation, computed tomography with three-dimensional reconstruction of the skull showed premature fusion of the left coronal and metopic sutures in both twins. They underwent craniofacial reconstruction at the 9th month of age using a combination of techniques. The postoperative outcomes were satisfactory in both cases., Conclusion: To the best of our knowledge, this is the first case report to describe the occurrence of complex craniosynostosis (CCS) in children with PTHS. Further studies are needed to determine whether the co-occurrence of PTHS and CCS described here indicates an association or is explained by chance., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Bain type of X-linked syndromic intellectual developmental disorder, caused by pathogenic missense variants in HRNRPH2, was initially described in six female individuals affected by moderate-to-severe neurodevelopmental delay. Although it was initially postulated that the condition would not be compatible with life in males, several affected male individuals harboring pathogenic variants in HNRNPH2 have since been documented. However, functional in-vitro analyses of identified variants have not been performed and, therefore, possible genotype-phenotype correlations remain elusive. Here, we present eight male individuals, including a pair of monozygotic twins, harboring pathogenic or likely pathogenic HNRNPH2 variants. Notably, we present the first individuals harboring nonsense or frameshift variants who, similarly to an individual harboring a de novo p.(Arg29Cys) variant within the first quasi-RNA-recognition motif (qRRM), displayed mild developmental delay, and developed mostly autistic features and/or psychiatric co-morbidities. Additionally, we present two individuals harboring a recurrent de novo p.(Arg114Trp), within the second qRRM, who had a severe neurodevelopmental delay with seizures. Functional characterization of the three most common HNRNPH2 missense variants revealed dysfunctional nucleocytoplasmic shuttling of proteins harboring the p.(Arg206Gln) and p.(Pro209Leu) variants, located within the nuclear localization signal, whereas proteins with p.(Arg114Trp) showed reduced interaction with members of the large assembly of splicing regulators (LASR). Moreover, RNA-sequencing of primary fibroblasts of the individual harboring the p.(Arg114Trp) revealed substantial alterations in the regulation of alternative splicing along with global transcriptome changes. Thus, we further expand the clinical and variant spectrum in HNRNPH2-associated disease in males and provide novel molecular insights suggesting the disorder to be a spliceopathy on the molecular level., (© 2021. The Author(s).)

We studied the association between episodic memory and cortical fibrillar β-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([ 11 C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [ 11 C]PiB uptake (p's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective intrauterine growth restriction (sIUGR), which were classified according to the umbilical artery (UA) Doppler flow pattern of the IUGR twin., Methods: This was a retrospective cohort study of all MCDA twin pregnancies diagnosed with sIUGR and managed at a single tertiary referral center between 2012 and 2018. Cases were classified according to the UA Doppler flow pattern of the IUGR twin as Type I (positive end-diastolic flow), Type II (persistently absent/reversed end-diastolic flow) or Type III (intermittently absent/reversed end-diastolic flow). Patients with Type-II or -III sIUGR were hospitalized at 26-28 weeks of gestation for increased fetal surveillance. Perinatal and immediate and long-term neurodevelopmental outcomes were stratified according to the UA Doppler flow pattern at the final examination. Intact survival rate was defined as the number of infants surviving without neurological impairment, divided by the total number of fetuses. Composite adverse outcome, defined as any mortality, presence of severe brain lesions on postnatal transcranial ultrasound or severe neurological morbidity, was also assessed., Results: Of 88 MCDA twin pregnancies with sIUGR included in the study, 28 underwent selective termination by cord occlusion using radiofrequency ablation, resulting in a perinatal survival rate of 89.3% and a median gestational age (GA) at delivery of 33.8 (interquartile range (IQR), 28.8-38.2) weeks for the large cotwin. Expectant management was employed in 60 cases. In 26 (43.3%) cases in the expectant-management group, the classification according to the UA Doppler flow pattern changed during gestation, resulting in 26 (43.3%) cases of Type-I, 22 (36.7%) cases of Type-II and 12 (20.0%) cases of Type-III sIUGR at the final examination. The perinatal survival rate of both twins with sIUGR Types I, II and III at the final examination was 100%, 81.8% and 75.0%, respectively (P = 0.04). Two cases of double fetal death and one case of single fetal death occurred 1-4 weeks after the Doppler pattern had changed from Type I or Type II to Type III. The median GA at delivery was 34.8 (IQR, 33.1-35.7) weeks in Type I, 30.3 (IQR, 28.6-32.1) weeks in Type II and 32.0 (IQR, 31.3-32.6) weeks in Type III (P < 0.01). The total intact survival rate was 100% for Type I, 77.3% for Type II and 75.0% for Type III (P < 0.001). Multivariate analysis demonstrated that early GA at diagnosis (odds ratio (OR), 0.83 (95% CI, 0.69-0.99); P = 0.04) and the presence of Type II or III vs Type I at the last examination (OR, 13.16 (95% CI, 1.53-113.32); P = 0.02) were associated with preterm birth < 32 weeks' gestation. Early GA at diagnosis was also associated with the composite adverse outcome (OR, 0.60 (95% CI, 0.36-0.99); P = 0.04)., Conclusions: The classification system of MCDA pregnancy complicated by sIUGR, according to the UA Doppler flow pattern of the IUGR twin at final examination, is associated with perinatal outcome. Importantly, the UA Doppler flow pattern can change during gestation, which has an impact on the risk of fetal death. Nevertheless, under strict fetal surveillance, the perinatal outcome of these pregnancies is favorable. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate the association between intrauterine growth restriction (IUGR) and the incidence of fetuses with patent ductus arteriosus (PDA) and Hemodynamically significant PDA (Hs-PDA) in dichorionic twins (DC) with selective IUGR., Materials and Methods: This is an observational cohort study and retrospective case assessment, involved twins born at Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan between 2013 and 2018. DC twins with selective IUGR (sIUGR) were defined as the presence of a birth weight discordance of >25% and a smaller twin with a birth weight below the tenth percentile. PDA was diagnosed using echocardiography between postnatal day 3 and 7. Hs-PDA was defined as PDA plus increased pulmonary circulation, poor systemic perfusion, cardiomegaly, pulmonary edema, or hypotension requiring pharmacotherapeutic intervention., Result: A total of 1187 twins were delivered during the study period, and 53 DC twins with selective IUGR were included in this study. DC twins with PDA have higher rate of preterm birth, lower gestational age of delivery, and lower mean birth weight of both twins compared with DC twins without PDA. In a comparison of the sIUGR twin with the appropriate for gestational age co-twin, both the incidences of PDA (28.30% vs. 7.55%, respectively; P = 0.003) and Hs-PDA (24.53% vs. 5.66%, respectively; P = 0.002) were higher in sIUGR fetuses than in the appropriate for gestational age co-twins. Small gestational age of delivery was the only variable to predict PDA and Hs-PDA [p = 0.002, Odds ratio = 0.57 (0.39-0.82), p = 0.009, Odds ratio = 0.71 (0.55-0.92), respectively]., Conclusion: An analysis of dichorionic twins with sIUGR indicated that IUGR increased the risk of PDA and hemodynamically significant PDA., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Brain injury of the surviving twin from monochorionic pregnancies following intrauterine fetal demise during the second and third trimesters is a rare but severe complication. Monochorionicity and gestational age at the time of stillbirth seem to be decisive factors in terms of long-term neurologic outcome prediction for the survivor. Magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) in particular, seem to bring the earliest and most accurate diagnosis. Ultrasound detection of brain damage is possible in later stages of fetal brain injury. It is essential to provide early diagnosis and multidisciplinary counsel to the parents to ensure informed decision making. For couples who choose to terminate pregnancy legislation related to late abortion might lead to further distress. Our paper aims to stress the importance of MRI DWI in the evaluation of surviving twins following single intrauterine fetal demise in monochorionic pregnancies and the delicate context of the medical professionals and parents facing this clinical situation, sometimes complicated by legal constraints., (© 2021 Gheorghe Cruciat et al., published by De Gruyter, Berlin/Boston.)

Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatment may be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: To describe an innovative alternative to exploratory laparotomy in a newborn with a sub capsular hepatic hematoma secondary to umbilical vein catheterization., Clinical Case: A preterm baby with a history of hyaline membrane disease, pulmonary hypertension, and large patent ductus arteriosus, requiring mechanical ventilation and the use of vasoactive drugs. Umbilical catheters were inserted and through an abdomen X-ray, we observed their proper position. The patient evolved with greater requirements of vasoactive drugs, abdominal wall pallor, and abdominal distention. Abdominal ultrasound showed a subcapsular hepatic hematoma, with no signs of active bleeding, so expectant management was decided. The patient required increased vasoactive drugs and presented a decrease in hematocrit. New ultrasound showed a larger subcapsular hematoma, abundant perihe patic fluid, and the intraparenchymal position of the umbilical catheter was confirmed. Endovascular embolization was performed through the umbilical catheter with Gelita®, achieving occlusion of the capsular path. Posterior ultrasound showed a reduction of the hematoma., Conclusions: The use of embolization through angiography is not commonly used in pediatric emergencies. It is a procedure with fewer comorbidities and complications than exploratory laparotomy, therefore it should be considered as first-line therapy in patients like the one presented above. The limitation for its routine performance is the lack of available angiography operating room and trained interventional radio logy team.

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant disease that leads to premature cardiovascular disease (CVD). Since monozygotic twins share the intrauterine environment and have the same age and gene profile, they could represent a very special resource for the investigation of the causes and the natural course of FH. This report is a description of 36-year-old monozygotic twin brothers with almost identical early coronary artery involvement due to FH concomitant with high lipoprotein(a) (Lpa) levels and a review of the literature. Sequence analysis revealed that the twins were homozygous for the LDLR c.1060+10G>A (rs12710260) mutation and heterozygous for the LDLR c.542C>T (rs557344672) mutations. Both were also homozygous for the c.1060+7T>C (rs2738442) and c.1586+53A>G (rs1569372) mutations in the LDLR gene as well as c.4265A>T (rs568413) mutations in the APOB gene. In the literature, there are 7 twin cases with reported FH, but none with high Lpa levels. The HoFH twins in this case report had lower low-density lipoprotein (LDL) cholesterol levels than expected (before treatment 204 and 223 mg/dL), with almost identical coronary involvement. Both had an extremely high Lpa level (308 and 272 nmol/L) with a very low coronary calcium score (16 AU) and a good response to statins (>60%). There was a history of the first CVD event occurring at nearly the same age (32-34 years) in the family. This could be an important aspect of FH families as a result of the similar timing of cumulative LDL exposure exceeding the threshold of CVD events. In conclusion, this first report of monozygotic HoFH twins with elevated Lpa levels and almost identical early coronary artery involvement at the same age provides evidence to substantiate the hypothesis of lifetime cholesterol burden/exposure.

Due to the special circumstances and the pre-natal environment in twin gestations, disruptions in the development of the embryo are more frequently observed in twin births as compared to singleton births. Twin research provides an excellent model to explore the etiology of disruptions in craniofacial biology. Mirror imaging (MI) is a special manifestation of twinning, and the elucidation of the etiology of this phenomenon is important to understand the biological mechanisms which underlie congenital defects, like orofacial clefts, and to provide insight into left-right asymmetry. The aim of this paper was, therefore, to present 3 pairs of Turkish monozygotic (MZ) twins with MI dental features, and to contribute to the knowledge of the MI phenomenon in the literature. We examined 2 male and 1 female MZ twin pairs clinically and radiographically in terms of their MI features. Mirrorimage features in dental and other ectodermal structures were detected in all the twins. Understanding the biological mechanisms of MI provides broad insight into preventive measures and treatment protocols. Furthermore, the presence of MI features may lead to the detection of other MI pathologies in twins.

Disorders of the white matter are genetically very heterogeneous including several genes involved in mitochondrial bioenergetics. Diagnosis of the underlying cause is aided by pattern recognition on neuroimaging and by next-generation sequencing. Recently, genetic changes in the complex I assembly factor NUBPL have been characterized by a consistent recognizable pattern of leukoencephalopathy affecting deep white matter including the corpus callosum and cerebellum. Here, we report twin boys with biallelic variants in NUBPL, an unreported c.351 G > A; p.(Met117Ile) and a previously reported pathological variant c. 693 + 1 G > A. Brain magnetic resonance imaging showed abnormal T2 hyperintense signal involving the periventricular white matter, external capsule, corpus callosum, and, prominently, the bilateral thalami. The neuroimaging pattern evolved over 18 months with marked diffuse white matter signal abnormality, volume loss, and new areas of signal abnormality in the cerebellar folia and vermis. Magnetic resonance spectroscopy showed elevated lactate. Functional studies in cultured fibroblasts confirmed pathogenicity of the genetic variants. Complex I activity of the respiratory chain was deficient spectrophotometrically and on blue native gel with in-gel activity staining. There was absent assembly and loss of proteins of the matrix arm of complex I when traced with an antibody to NDUFS2, and incomplete assembly of the membrane arm when traced with an NDUFB6 antibody. There was decreased NUBPL protein on Western blot in patient fibroblasts compared to controls. Compromised NUBPL activity impairs assembly of the matrix arm of complex I and produces a severe, rapidly-progressive leukoencephalopathy with thalamic involvement on MRI, further expanding the neuroimaging phenotype., Competing Interests: Declaration of Competing Interest JVH participates in clinical trials of mitochondrial disorders by Stealth Biotherapeutic, Inc. RPS participates in clinical trials of mitochondrial disorders by Bioelectron Therapeutics, Stealth Biotherapeutics, Inc. and a National Institutes of Health funded phase 3 trial of dichloroacetate in pyruvate decarboxylase deficiency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although intertwin size difference is an important measure of fetal growth, the appropriate cut point to define discordance is unclear. Few studies have assessed intertwin differences in estimated fetal weight longitudinally or in relation to size differences at birth., Objectives: The objectives of the study were to estimate the magnitude of percentage differences in estimated fetal weight across gestation in dichorionic twins in relation to a fixed discordance cut point and compare classification of aberrant fetal growth by different measures (estimated fetal weight differences, birthweight discordance, small for gestational age)., Study Design: Women aged 18-45 years from 8 US centers with dichorionic twin pregnancies at 8 weeks 0 days to 13 weeks 6 days gestation planning to deliver in participating hospitals were recruited into the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Dichorionic Twins study and followed through delivery (n = 140; 2012-2013). Ultrasounds were conducted at 6 targeted study visits to obtain fetal biometrics and calculate estimated fetal weight. Percent estimated fetal weight and birthweight differences were calculated: ([weight larger - weight smaller ]/weight larger )*100; discordance was defined as ≥18% for illustration. Birth sizes for gestational age (both, 1, or neither small for gestational age) were determined; twins were categorized into combined birthweight plus small for gestational age groups: birthweight discordance ≥18% (yes, no) with both, 1, or neither small for gestational age. Linear mixed-models estimated percentiles of estimated fetal weight percent differences across gestation and compared estimated fetal weight differences between combined birthweight discordance and small for gestational age groups. A Fisher exact test compared birthweight discordance and small for gestational age classifications., Results: Median estimated fetal weight percentage difference increased across gestation (5.9% at 15.0, 8.4% at 38.0 weeks), with greater disparities at higher percentiles (eg, 90th percentile: 15.6% at 15.0, 26.3% at 38.0 weeks). As gestation advanced, an increasing percentage of pregnancies were classified as discordant using a fixed cut point: 10% at 27.0, 15% at 34.0, and 20% at 38.0 weeks. Birthweight discordance and small for gestational age classifications differed (P = .002); for birthweight discordance ≥18% vs <18%: 44% vs 71% had neither small for gestational age; 56% vs 18% had 1 small for gestational age; no cases (0%) vs 11% had both small for gestational age, respectively. Estimated fetal weight percent difference varied across gestation by birthweight discordance plus small for gestational age classification (P = .040). Estimated fetal weight percentage difference increased with birthweight discordance ≥18% (neither small for gestational age: 0.46%/week [95% confidence interval, 0.08-0.84]; 1 small for gestational age: 0.57%/week [95% confidence interval, 0.25-0.90]) but less so without birthweight discordance (neither small for gestational age: 0.17%/week [95% confidence interval, 0.06-0.28]; 1 small for gestational age: 0.03%/week [95% confidence interval, -0.17 to 0.24]); both small for gestational age: 0.10%/week [95% confidence interval, -0.15 to 0.36])., Conclusion: The percentage of dichorionic pregnancies exceeding a fixed discordance cut point increased over gestation. A fixed cut point for defining twin discordance would identify an increasing percentage of twins as discordant as gestation advances. Small for gestational age and percentage weight differences assess distinct aspects of dichorionic twin growth. A percentile cut point may be more clinically useful for defining discordance, although further study is required to assess whether any specific percentile cut point correlates to adverse outcomes., (Published by Elsevier Inc.)

Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin causing the acardiac body to be hypoxemic. In this report, we present an acardius anceps, therapeutically laser separated from its pump twin at 16 weeks. The healthy pump twin and macerated acardiac body were born at 40 3/7 weeks. A three dimensional (3D) reconstruction was made by CT images, showing cranial bones, spinal column, pelvis and lower extremities but absent arms. A cyst in the neck of the acardiac twin was identified by postnatal sonography; this was also described in four literature cases, and was additionally observed by us in two other acardiac twins. Median cleft palate was identified by oral cavity inspection but undetectable in the reconstruction. In the literature, we found 21 other acardiac anceps twins with a cleft palate. From the two larger published series, with 12 clefts in 21 acardiac anceps twins, a cleft palate occurs in over 50% during acardiac twinning. Our first hypothesis is that acardiac fetuses develop an oral cleft palate when acardiac onset starts prior to 11 weeks, because 11 weeks includes the period of embryonic oral cavity formation, and no cleft occurs when onset starts later than 11 weeks. Our second hypothesis is that cysts and cleft palates are more common in acardiac twins than currently known, likely reflecting that acardiac bodies are hypoxemic and that hypoxia contributes to the development of both cysts and clefts., (© 2019 Wiley Periodicals, Inc.)

The twin birth rate is increasing in the United States. Twin pregnancies can be dichorionic or monochorionic (MC). MC twins account for 20% of twin pregnancies but 30% of all-cause pregnancy-related complications. This article describes the imaging findings that establish chorionicity and amnionicity. Ideally, these are established in the first trimester when accuracy is high, but they can also be determined later in pregnancy. Complications unique to MC twin pregnancy include twin-twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion sequence, and selective fetal growth restriction. The US features, staging systems, and management of these complications are reviewed, and the consequences of MC twin demise are illustrated. Ongoing surveillance for these conditions starts at 16 weeks gestation. Monoamniotic (MA) twins are a small subset of MC twins. In addition to all of the MC complications, specific MA complications include cord entanglement and conjoined twinning. Radiologists must be able to determine chorionicity and amnionicity and should be aware of potential complications so that patients may be referred to appropriate regional specialized centers. A proposed algorithm for referral to specialized fetal treatment centers is outlined. Online supplemental material is available for this article. © RSNA, 2019.

Background: Birthweight discordance is well studied, with less known about longitudinal inter-twin differences in foetal growth., Objective: To examine inter-twin per cent differences in EFW (EFW % ), head (HC % ) and abdominal circumference (AC % ), and femur length (FL % ) across gestation in dichorionic twin gestations and explore associated characteristics., Methods: Foetal biometrics were assessed by ultrasound and EFW calculated at ≤6 study visits among women with dichorionic twin pregnancies enrolled in the NICHD Fetal Growth Studies cohort (US, 2012-2013). Inter-twin per cent difference was defined: ([Size larger twin  - Size smaller twin ]/Size larger twin  × 100). Linear mixed models evaluated per cent differences in foetal biometrics at 15 weeks and their change per week overall and by maternal/neonatal characteristics in unadjusted and adjusted models., Results: In 140 pregnancies, inter-twin per cent differences increased across gestation for EFW (0.18%/week, 95% confidence interval [CI] 0.10, 0.27), HC (0.03%/week, 95% CI 0.00, 0.06), and AC (0.03%/week, 95%CI -0.01, 0.08) but decreased for FL (-0.03%/week, 95% CI -0.09, 0.02). After adjustment, change in EFW % difference across gestation differed by pre-pregnancy body mass index (BMI [kg/m 2 ]; underweight [<18.5]; normal weight [18.5-24.9]; overweight [25.0-29.9]; obese [≥30.0]; P interaction  = .022); and conception method (in vitro fertilisation [IVF], intrauterine insemination, ovulation induction medication, donor egg/embryo, none; P interaction  = .060). While EFW % difference increased with normal pre-pregnancy BMI (0.24%/week, 95% CI 0.12, 0.37), little change was noted with pre-pregnancy obesity (0.01%/week, 95% CI -0.15, 0.17). EFW % difference increased in conceptions without fertility treatments (0.23%/week, 95% CI 0.11, 0.34) but not IVF conceptions (-0.00%/week, 95% CI -0.16, 0.16). Similar patterns of differences across gestation were noted for HC % by conception method (P interaction  = .026) and AC % by pre-pregnancy BMI (P interaction  = .071); changes in HC % differed by parity (nulliparous, multiparous; P interaction  = .004)., Conclusions: EFW % difference increased across gestation in dichorionic twins, but remained stable with pre-pregnancy obesity or IVF conception, patterns mirrored for HC and AC. Research is needed to understand pathologic versus physiologic differential twin growth trajectories., (© 2019 John Wiley & Sons Ltd.)

Cerebral cavernous malformations are focal vascular lesions of the brain, occurring sporadically or as an autosomal dominant familial form. The genetic background influences not only the clinical course but also patients' consultation and the indication to treat. We here present the rare case of monozygotic male twins of a polyzygotic triplet birth, carrying a CCM1 mutation, inherited from the mother. Both twins showed an identical site and size of a large frontobasal lesion. The genetic segregation and the clinical course in affected family members are presented and discussed.

Our recent study has demonstrated that increased connectivity in the cerebello-thalamo-cortical (CTC) circuitry is a state-independent neural trait that can potentially predict the onset of psychosis. One possible cause of such "trait" abnormality would be genetic predisposition. Here, we tested this hypothesis using multi-paradigm functional magnetic resonance imaging (fMRI) data from two independent twin cohorts. In a sample of 85 monozygotic (MZ) and 52 dizygotic (DZ) healthy twin pairs acquired from the Human Connectome Project, we showed that the connectivity pattern of the identified CTC circuitry was more similar in the MZ twins (r = 0.54) compared with that in the DZ twins (r = 0.22). The structural equation modeling analysis revealed a heritability estimate of 0.52 for the CTC connectivity, suggesting a moderately strong genetic effect. Moreover, using an independent schizophrenia cotwin sample (10 discordant MZ cotwins, 30 discordant DZ cotwins, and 32 control cotwins), we observed a significant linear relationship between genetic distance to schizophrenia and the connectivity strength in the CTC circuitry (i.e., schizophrenia MZ cotwins > schizophrenia DZ cotwins > control twins, P = 0.045). The present data provide converging evidence that increased connectivity in the CTC circuitry is likely to be a heritable trait that is associated with the genetic risk of schizophrenia.

Intraventricular hemorrhage is bleeding into the fluid-filled areas (ventricles) inside the brain. The condition occurs most often in babies that are born premature, growth restricted and twins pregnancies. Abnormal platelets number or functions are responsible greatly for this condition. We presented here a pregnant woman had thrombasthenia at 28 weeks of gestation with ultrasound findings of intraventricular haemorrhage in her both ICSI twin's fetuses., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The literature is certain regarding the multifactorial etiology of rotator cuff degeneration. However, it remains unclear if rotator cuff degeneration exclusively depends on intrinsic and extrinsic factors or if it is also genetically determined. We compared the health status of cuff tendons, evaluated with a magnetic resonance imaging (MRI) study, between elderly monozygotic and dizygotic twins with the aim of separating the contributions of genetics from shared and unique environments., Methods: The rotator cuff tendon status was assessed using the Sugaya classification by MRI. Heritability, defined as the proportion of total variance of a specific characteristic in a particular population due to a genetic cause, was calculated as twice the difference between the intraclass correlation coefficients for monozygotic and dizygotic pairs. The influence of shared environment, which contributes to twin and sibling similarity, was calculated as the difference between the monozygotic correlation coefficient and the heritability index., Results: We identified 33 pairs of elderly twins: 17 monozygotic pairs and 16 dizygotic pairs, with a mean age (and standard deviation) of 64.62 ± 3.32 years. The polychoric correlation was 0.62 in monozygotic twins and 0.53 in dizygotic twins. The calculated heritability index was 0.18 (18%), and the contribution was 0.44 (44%) for the shared environment and 0.38 (38%) for the unique environment., Conclusions: The role of genetics in rotator cuff degeneration is quantified by our study on elderly monozygotic and dizygotic twins; however, it is only partial with respect to the contribution of shared and unique environments.

Background: The fasting-state serum bile acid profile in nonalcoholic fatty liver disease (NAFLD) has been reported to differ when nonalcoholic steatohepatitis is compared to nonalcoholic fatty liver. However, there are few data comparing changes in NAFLD vs non-NAFLD, or whether the bile acid profile differs according to the degree of fibrosis., Aim: To examine the serum bile acid profile across the entire spectrum of NAFLD., Methods: We performed a cross-sectional analysis of two complementary cohorts: a Twin and Family cohort of 156 participants, and a biopsy-proven-NAFLD cohort of 156 participants with fasting bile acid profiling using liquid chromatography/mass spectrometry., Results: In the Twin and Family cohort (mean age 46.3 years and body mass index (BMI) 26.6 kg/m 2 ), 36 (23%) participants had NAFLD (magnetic resonance imaging proton density fat fraction ≥ 5%). Higher chenodeoxycholyl conjugates (9.0% vs 6.5%, P = 0.019) and lower glycohyocholate (1.2% vs 3.6%, P < 0.001) were observed in NAFLD compared to non-NAFLD-controls. In the biopsy-proven-NAFLD cohort (mean age 49.8 years, BMI 32.0 kg/m 2 ), no differences in total bile acid were seen between nonalcoholic fatty liver vs nonalcoholic steatohepatitis. The total unconjugated bile acid significantly decreased across nonalcoholic steatohepatitis categories (P = 0.044). The distribution of stage of fibrosis was F0: 42.3%, F1: 32.7%, F2: 10.3%, F3: 8.3% and F4: 6.4%. The total serum bile acid increased with increase in fibrosis stage (P < 0.001). The primary conjugated bile acid proportion increased (P < 0.001) whereas unconjugated bile acid (P = 0.006), unconjugated cholyl (P < 0.001) and chenodeoxycholyl conjugates (P < 0.002) significantly decreased with increase in liver fibrosis stage., Conclusions: Fasting-state serum bile acid profile alterations are seen across the entire spectrum of NAFLD. The total serum bile acids did not differ significantly between NAFLD vs non-NAFLD and nonalcoholic fatty liver vs nonalcoholic steatohepatitis, but were significantly perturbed progressively as liver fibrosis increases., (© 2018 John Wiley & Sons Ltd.)

Introduction: We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin., Materials and Methods: This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography., Results: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins., Discussion: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option., (© 2018 S. Karger AG, Basel.)

Rationale: Sirenomelia is a very rare congenital malformation and characterized by fused lower extremities, oligohydramnios, renal agenesis, absent urinary tract and external genitalia, single umbilical artery, and imperforate anus. Ultrasonography is an optimal method for prenatal screening and diagnosis of sirenomelia. The incidence of sirenomelia in the twin pregnancy is extremely low., Patient Concerns: We reported a case of 1 twin with sirenomelia in dichorionic-diamniotic twin pregnancy after in vitro fertilization and embryo transfer., Diagnoses: The sirenomelia twin was diagnosed at the 2nd trimester by ultrasonic examination and complicated with oligohydramnios and a single umbilical artery, another twin was normal., Interventions: A regular and careful antenatal care was conducted. The parents refused to examine the chromosome of sirenomelia twin, and the chromosomal microarray analysis of the amniotic fluid sample was only achieved in the normal anatomy twin after extensively counseled by the multi-disciplinary team., Outcomes: At 34+2 gestational weeks, the demise of the malformed twin occurred, while fetal heart rate monitoring of the normal twin was abnormal, and an emergency cesarean section was performed. A healthy male baby was delivered with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively. The mother and the baby were followed up and are in good health until now., Conclusion: Sirenomelia is a lethal condition in the perinatal period. Early antenatal diagnosis is very important. Voluntary selective termination of sirenomelia 1 in twin pregnancy may be advised. Expecting parents should be counseled by the multidisciplinary team about the management and prognosis of the sirenomelia.

Background: Monochorionic twin pregnancies are high-risk, however at present, no screening test is available to predict which monochorionic twin pregnancy will develop complications., Objective: We sought to assess ability of first-trimester pregnancy-related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies., Data Sources: Data sources were MEDLINE, Embase, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to May 12, 2017. Gray literature and bibliographies of articles were checked., Study Eligibility Criteria: Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic-diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed, were included., Study Appraisal and Synthesis Methods: Quality assessment was evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I 2 and publication bias was visually assessed by funnel plots and quantitatively by Egger test., Results: In all, 48 studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: nuchal translucency >95th centile in one/both fetuses and twin-twin transfusion syndrome (odds ratio, 2.29 [95% confidence interval, 1.05-4.96], I 2  = 6.6%, 4 studies, 615 pregnancies); crown-rump length discordance ≥10% and twin-twin transfusion syndrome (odds ratio, 2.43 [95% confidence interval, 1.13-5.21], I 2  = 14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and twin-twin transfusion syndrome (odds ratio, 2.12 [95% confidence interval, 1.17-3.83], I 2  = 0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation., Conclusion: It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first-trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Generalized arterial calcification of infancy (GACI) is a rare genetic disorder with high infantile mortality, described to be due to ENPP1, and less commonly ABCC6 mutations. Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Without therapy, patients will die before 6 months of age. Our patient is now 3 years old, former recipient twin of twin-to-twin transfusion syndrome (TTTS). Initial fetal echocardiogram at 19 weeks showed calcifications of the ascending aorta and pulmonary artery (PA). She underwent utero laser therapy, and despite resolution of the TTTS, her follow-up scans showed progressive calcification of the aorta and PA. Postnatal echocardiogram showed calcification and supravalvar stenosis of the aorta and PA. CT on day of life 6 showed calcifications in the PAs, aortic arch, and descending aorta. Quantification of valvular calcification can be difficult; in our patient, increasing outflow tract gradient on echocardiogram was used to monitor disease progression. Molecular testing revealed an ABCC6 gene mutation. She was started on weekly IV pamidronate (0.1-0.3 mg/kg/week) on day 8 of life then transitioned to oral etidronate (15-20 mg/kg/day). Given progressive supravalvar aortic and pulmonary stenosis, she underwent surgical repair with patch augmentation of the PA and ascending aorta at 4 months old. She has done well post-operatively, continuing on enteral bisphosphonate therapy with no side effects to date. Her identical twin was confirmed to have the same mutation and remains asymptomatic with no calcifications. Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Echocardiographic evaluation can be used to monitor disease progression by arterial gradients. Molecular testing is also essential to evaluate for possible co-morbidities in these patients and pregnancy management for the future.

Background: Chiari III malformation is an extremely rare congenital anomaly. At present, its primary and associated pathognomonic factors remain poorly understood. The authors report a case of a male neonate born with an occipital encephalocoele with herniation of posterior fossa contents associated with bilateral postaxial polydactyly., Case Description: The patient is a dichorionic, diamniotic twin conceived via assisted reproductive methods; his twin sister has no congenital anomaly. Neurosurgical management included successful repair of the encephalocoele and subsequent cerebrospinal fluid diversion via a ventriculoperitoneal shunt., Conclusions: Owing to the uniqueness of this patient's presentation, the concurrent diagnoses of Chiari III malformation and polydactyly are discussed in concordance with updated literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To report the outcomes of selective reduction (SR) in dichorionic twins complicated by pre-viable, premature rupture of membranes (PV-PROM)., Methods: Retrospective case series. Ultrasound database was searched for cases of dichorionic twin pregnancy with PV-PROM, either managed conservatively or with SR. Chart reviews were done for these cases. Simple descriptive statistics were used where appropriate., Results: Twenty-two cases of expectantly managed dichorionic twins complicated by PV-PROM with delivery information were available for analysis. Mean GA at PV-PROM was 20.6 weeks, mean GA of delivery was 27.6 weeks, and the mean latency was 39.6 days. There were five cases of SR following PV-PROM in dichorionic twin pregnancies. Mean GA of PV-PROM was 17.0 weeks. Average time from PV-PROM to procedure was 2.5 weeks. Mean GA of delivery of the surviving fetus was 32.6 weeks (P = 0.20) with mean latency of 108 days (P = 0.06). Twelve additional cases have been published and are summarized along with our five cases., Conclusion: There was a trend towards an increase in latency interval between cases of PV-PROM managed by SR and expectant management in our institution. When combined with the existing literature data, there may be an improvement in latency., (Copyright © 2018. Published by Elsevier Inc.)

In the decades since the introduction of ultrasound into routine obstetric practice, the advantages of ultrasound have moved beyond the simple ability to identify multiple pregnancies antenatally to the possibility of screening them for fetal anomalies, pre-eclampsia, preterm birth, and the complications specific to monochorionic pregnancies. Screening studies have often excluded twins because physiological differences impact on the validity and sensitivity of the screening tests in routine use in singletons, and therefore, the evidence of screening performance in multiple pregnancy lags behind the evidence from singleton pregnancies. In general, most pregnancy complications are more common in twin pregnancy, but screening tests are less accurate or well validated. In this review article we present the current state of the evidence and avenues for future research relating to the use of ultrasound and screening for complications in twin pregnancies, including the monochorionicity-related pathologies, such as twin-twin transfusion syndrome, selective growth restriction, twin anaemia-polycythaemia sequence and twin reversed arterial perfusion sequence., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the perinatal and postnatal risk factors for various brain pathologies among preterm twins., Methods: Retrospective data of 104 twin pairs of which one of the siblings had evidence of abnormal head ultrasound (HUS) and its co-twin with normal HUS served as control., Results: Abnormal HUS consisted of periventricular echodensities among 69 infants, intraventricular hemorrhage among 28 infants, cystic periventricular leukomalacia among 10 infants, and other parenchymal brain pathologies among 5 infants. Perinatal and postnatal complications were similar between study and controls. Siblings with severe brain pathologies were ventilated for longer time over their co-twins. In 10 out of 11 cases of discordant twins (≥20%) with severe brain pathology, the severe pathology was recorded in the larger sibling., Conclusions: Our study results, which included matched preterm twin pairs for study/control groups to evaluate risk factors for the overall evidence of brain injury, could not determine specific risk factors for these brain pathologies. The finding that severe brain pathologies were more common among the larger co-twin requires further study of and attention to short- and long-term outcomes and the potential conflicts that may arise.

Umbilical cord entanglement is the leading cause of fetal mortality in monoamniotic twin pregnancies and a pseudo monoamniotic environment. Published methods for detecting this complication include color Doppler and pulsed Doppler sonography; however, no method provides an absolute diagnosis. In this case, we report the diagnosis of umbilical cord entanglement using dual-gate Doppler imaging. A 35-year-old woman was referred to our hospital at 28 weeks of gestation for prenatal management because of diagnosis of a monochorionic diamniotic twin pregnancy with spontaneous septostomy of the dividing membranes. Each fetus displayed normal fetal growth without obvious discordance and anatomical abnormalities. However, the dividing membrane was not detected, and an entangled cord was suspected. Dual-gate Doppler examination was carried out. Two regions of interest were considered at different areas of the umbilical arteries, and when each Doppler image showed two different heart rates at the same time, we considered this to be evidence of umbilical cord entanglement. Cesarean section was performed at 32 weeks of gestation and twins were delivered. The delivered umbilical cords had sixfold entanglement. In this case, dual-gate Doppler seems to have been more accurate than conventional single-gate Doppler for the diagnosis of cord entanglement because we confirmed two different heart rates at the same time with dual-gate Doppler.

Selective intrauterine growth restriction (sIUGR) affects 10-15% of all monochorionic pregnancies. Early severe forms are associated with intrauterine demise or neurological adverse outcome for both twins. The characteristics of umbilical artery (UA) Doppler in the IUGR fetus determine three clinical types: (I) normal UA Doppler and associated with good prognosis; (II) persistently absent/reverse UA end-diastolic flow and associated with early deterioration of the IUGR twin and very preterm delivery; (III) intermittently absent/reverse end-diastolic flow in the UA, and associated with unexpected fetal demise or neurological injury in one or both twins. Types II and III pose important challenges for management. Placental laser or cord occlusions do not seem to increase survival, but they might improve the outcomes of the larger twin. The use of an algorithm with severity criteria may help in counseling and planning management., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern of the smaller twin., Methods: An electronic search of MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases (2000-2016) was performed. sIUGR was defined as the presence of one twin with an estimated fetal weight and/or abdominal circumference < 10 th or < 5 th percentile and classified according to the umbilical artery Doppler flow pattern of the smaller twin (Type I: persistently positive; Type II: persistently absent/reversed; Type III: intermittently absent/reversed). Primary outcomes were perinatal mortality, intrauterine death, neonatal death and double fetal loss. Secondary outcomes were neonatal morbidity, including abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, admission to neonatal intensive care unit and respiratory distress syndrome, deterioration of fetal status, gestational age at delivery and degree of birth-weight discordance. A composite adverse outcome, defined as the presence of any mortality or abnormal brain findings, was also assessed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was used to compute the summary odds ratios (ORs), mean differences (MD) and proportions for the different outcomes., Results: Thirteen studies (610 pregnancies) were included. The risk of perinatal mortality was higher in twins affected by Type II compared with Type I sIUGR (OR, 4.1 (95% CI, 1.6-10.3)), whereas there was no difference among the other variants of growth restriction. Risk of abnormal postnatal brain imaging was significantly higher in twins affected by either Type II (OR, 4.9 (95% CI, 1.9-12.9)) or Type III (OR, 8.2 (95% CI, 2.0-33.1)) sIUGR compared with Type I sIUGR. The risk for neonatal intensive care unit admission was higher in Type II compared with Type I sIUGR (OR, 18.3 (95% CI, 1.0-339.7)). Twin pregnancies affected by Type I sIUGR were delivered at a significantly later gestational age compared with Type II (MD, 2.8 (95% CI, 1.83-3.86) weeks) and Type III (MD, 2.1 (95% CI, 0.97-3.19) weeks). The degree of birth-weight discordance was higher in Type II compared with Type I (MD, 21.6% (95% CI, 9.9-33.2%)) and Type III (MD, 9.3% (95% CI, 3.8-14.9%)) sIUGR., Conclusion: Monochorionic twin pregnancies affected by Type II sIUGR are at a higher risk of perinatal mortality and morbidity compared with Type I. The likelihood of an abnormal outcome is usually not significantly different between sIUGR Types II and III, although the latter has an unpredictable clinical course. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs., Methods: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details., Results: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (F max total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures., Significance: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: To determine how prenatal ultrasound measurements of dividing membrane thickness correlate with postnatal histological measurements and chorionicity in twin gestations., Methods: This was a prospective, longitudinal cohort study of twin gestations. Dividing membrane thickness was measured by transabdominal ultrasound, with the insonation beam both parallel and perpendicular to the membrane, in the second or third trimester, depending on when care was established. Ultrasound examinations were performed every 4 weeks following initial assessment until delivery. Measurements of membrane thickness from the first ultrasound examination were compared with histological measurements after delivery., Results: A total of 45 twin pregnancies (32 dichorionic, 13 monochorionic) were included. Mean gestational age at initial ultrasound examination was 24.1 ± 7.3 weeks. Parallel ultrasound measurements of membrane thickness were 1.6 ± 0.8 mm for monochorionic and 2.5 ± 0.9 mm for dichorionic gestations (P = 0.001). Perpendicular ultrasound measurements were 1.6 ± 0.3 mm for monochorionic and 2.2 ± 0.8 mm for dichorionic gestations (P = 0.009). Inter- and intraobserver reliability of ultrasound measurements were 0.847 and 0.950, respectively. Parallel and perpendicular ultrasound measurements correlated better with each other (R = 0.807, P < 0.001) than with histological measurements of membrane thickness (R parallel  = 0.538, P < 0.001; R perpendicular  = 0.529, P < 0.001). Receiver-operating characteristics curve analyses to predict histological membrane thickness > 50 th percentile resulted in an area under the curve (AUC) of 0.828 for parallel (P < 0.001) and 0.874 for perpendicular (P < 0.001) measurements with a cut-off value of 1.9 mm for both approaches. The AUCs for parallel and perpendicular measurements to predict dichorionicity were 0.892 (P < 0.001) and 0.823 (P < 0.001) with cut-off values of 1.9 and 1.8 mm, respectively., Conclusion: Prenatal ultrasound measurement of twin dividing membrane thickness is positively correlated with postnatal histological measurement. Dichorionicity can be determined by a magnified dividing membrane thickness ≥ 1.9 mm. Measurements with the ultrasound beam parallel to the dividing membrane may be more accurate than perpendicular measurements. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

A case of monochorionic-monoamniotic (MCMA) twin pregnancy with growth discordance because of difference of cord diameter in forked umbilical cord is reported.MCMA twins were diagnosed at 12 weeks of gestation and twin growth discordance was considered during the follow-up twice-weekly visits to the ultrasound and prenatal care units. The pregnancy was terminated at 34 weeks. Two live female babies weighing 2510 g and 1940 g were delivered. Examination of placenta and umbilical cords after birth showed that the 2 cords merged into a conjoint cord 1 cm from insertion to the placenta (forked umbilical cord). Placental color injection showed that the 2 fetuses shared the same placenta area. The diameters of the 2 cords were significantly different (1.5 vs 0.8 cm). This caused an unequal distribution of blood and nutrients, which is the real reason of twin growth discordance in this case.This case reveals that the diameter discordance of cords can be an important factor for twin growth discordance. Few relevant cases have previously been reported. Cords diameter measurement is suggested for ultrasound surveillance of twin growth discordance.

Objective: The choice of a growth curve determines the screening for small-for-gestational-age (SGA) fetuses and little data is available on SGA twins. Our aim was to evaluate small-for-gestational-age (SGA) detection rate in twin pregnancies and assess whether the use of a customized curve allowed better identification of SGA fetuses., Study Design: Retrospective study including all twins between 2010 and 2013. Two groups were formed: the SGA and the non-SGA group. Four curves were compared: Hadlock's curve, a customized curve, EPOPé M0 and EPOPé M1. We defined a composite neonatal complication criterion (transfer to intensive care unit, respiratory distress and death)., Result: 472 fetuses were included with a 34.3% prevalence of SGA. Hadlock's curve showed better sensitivity for the detection of SGA <10th percentile (67.3% vs. 63%, 59.9% and 57.4% respectively). Diagnostic Odd Ratio were comparable for the detection of SGA. For the composite variable, there was a significant difference between the 2 groups using a customized curve adjusted for fetal sex (EPOPé M1)., Conclusion: The EPOPé (M0 and M1) and customized curves do not improve screening for SGA infants below the 10th percentile. The reduced effectiveness of customized curves can be related to the greater impact of placentation or cord insertion on the potential for fetal growth., (Copyright © 2017 Elsevier B.V. All rights reserved.)

An accessory navicular bone (AN) is the most common accessory ossicle in the foot. The presence of an AN bone can trigger various foot problems, such as posterior tibial tendon pathology, flattening of the medial longitudinal arch, and medial foot pain. Despite the clinical influence of presence of an AN in foot disease, the research regarding its inheritance is still insufficient. A total of 135 pairs of monozygotic (MZ) twins, 25 pairs of dizygotic (DZ) twins, and 676 singletons from families were enrolled in order to estimate genetic influences on AN. After confirmation of zygosity and family relationship with a tandem repeat marker kit and questionnaires, the presence and type of the AN was classified through bilateral feet radiographic examination. The heritability of an AN was estimated using quantitative genetic analysis based on a variance decomposition model considering various types of family relationships: father-offspring pair, mother-offspring pair, and pooled DZ twin and sibling pairs. As a result, approximately 40.96% of the participants in this study had an AN in either foot, with type II being the most common type. The heritability for the presence of any type of an AN in any foot was estimated as 0.88 (95% CI [0.82, 0.94]) after adjusting for age and sex. Specifically, type II AN showed the highest heritability of 0.82 (95% CI [0.71-0.93]). The high heritability of an AN found in this large twin and family study suggests that an AN is determined by the substantial influence of genetic factor.

Background: Familial cases of idiopathic intracranial hypertension (IIH) are exceedingly rare, and its occurrence in monozygotic twins has not been reported previously., Case Description: We report monozygotic female twins who developed IIH, one at age 25 years and the other at age 28 years. Continuous intracranial pressure (ICP) monitoring confirmed elevated ICP as measured initially by lumbar puncture. In both cases, successful treatment with resolution of papilledema and symptoms relief was achieved after ventriculoperitoneal shunting., Conclusions: This report documents the first case of IIH in monozygotic twins and the associated changes in ICP dynamics. Interestingly, almost equivalent alterations in ICP dynamics were found in the 2 patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A congenital coronary artery fistula (CAF) is a rare form of heart disease in which a coronary artery and a cardiac chamber or another vascular structure communicate. CAF could worsen ventricular perfusion and function, favoring ventricular ischemia and arrhythmias. To our knowledge, this is the first report of CAF, draining in the pulmonary artery, in two asymptomatic dizygotic twin brothers, diagnosed by echocardiography. Dizygotic twins are siblings with different genes exposed to the same environmental experience during the pregnancy. The occurrence of CAF (with similar instrumental findings) in both twin brothers could depend on a poorly identified environmental factor during pregnancy.

Objectives: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up., Methods: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable., Results: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02)., Conclusions: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Target genes in Alzheimer's disease (AD) have been identified. In monozygotic twins discordant for AD we analysed the expression of selected genes, and their possible regulation by epigenetic mechanisms in peripheral blood mononuclear cells, possibly useful to discover biomarkers. Amyloid precursor protein, sirtuin 1 and peptidyl prolyl isomerase 1 gene expressions were highly up-regulated in the AD twin versus the healthy one. Consistently with sirtuin 1 role in controlling acetylation status, we observed a substantial reduction of the acetylation on histone 3 lysine 9, associated with gene transcription in the AD twin. Noteworthy in the AD twin we also observed an increased gene expression in two histone deacetylases (HDACs) isoforms: HDAC2 and HDAC9. A general DNA hypomethylation of all gene promoters studied was also observed in both twins. Our results unravel transcriptional and epigenetic differences potentially helpful to better understand environmental factors and phenotypic differences in monozygotic twins., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Umbilical cord occlusion (UCO) utilizing laser photocoagulation is often not considered an option for selective termination after 20 weeks of gestation due to reported limitations of the procedure because of umbilical cord size. We compared outcomes after laser umbilical cord occlusion (L-UCO) before and after 20 weeks of gestation., Materials and Methods: We examined all patients with monochorionic- diamniotic twins and higher-order multiples (monoamniotic excluded) that underwent L-UCO at our facility between 2006 and 2014. Statistical analysis was performed using Fisher's exact and Kruskal-Wallis tests as appropriate., Results: Of 43 L-UCO cases, 11 cases (25.6%) had a discordant anomaly, and 32 cases (74.4%) had twin reversed arterial perfusion (TRAP) sequence. We achieved complete vascular occlusion in 100% (43/43) of cases of attempted L-UCO. There were 22 cases (51.2%) with gestational age ≤20 weeks, and 21 cases (48.8%) with gestational age >20 weeks. Perioperative patient characteristics and outcomes did not differ between the two groups. Survival rates were 90.9% (20/22) and 100% (21/21) at ≤20 weeks of gestation and >20 weeks of gestation, respectively., Discussion: The results of this study suggest that L-UCO is a reasonable surgical modality for patients prior to and beyond 20 weeks of gestation., (© 2016 S. Karger AG, Basel.)