Zika virus (ZIKV) is primarily known for its impact on the fetal central nervous system potentially leading to Congenital Zika Syndrome (CZS). Emerging evidence suggests ZIKV may also affect cardiac development. We conducted a follow-up study evaluating cardiologic findings in infants from ZIKV-exposed mothers. Infants born to mothers with PCR-confirmed ZIKV infection during pregnancy and/or who had positive ZIKV PCR results at birth received echocardiograms in the first year of life. Repeat imaging within 12 months was requested for infants with identified abnormalities. Frequencies of cardiovascular (CV) abnormalities were evaluated using Pearson χ2 test, Fisher's exact test, and descriptive statistics. Predictors of CV abnormalities were assessed using multivariate logistic regression, as well as univariate and multivariate prevalence estimates. Sensitivity analysis assessed the robustness of associations when stratified by age at echocardiography (early vs late). One hundred sixty-nine children with antenatal ZIKV-exposure had echocardiograms; 30.8% were microcephalic (MC). Thirty (17.8%) had cardiac anomalies. MC children had a higher frequency of CV abnormalities than normocephalic (NC) children (26.9% vs 13.7%, p = 0.04). Twenty-four of 30 children (80.0%) returned for repeat imaging; of that group, 25.0% continued to demonstrate defects. Rates of persistent defects between the MC vs. NC cohorts were 33.3% vs 16.7%, respectively (p = 0.64). Presence of CV defects was significantly associated with MC (OR=3.40, 95% CI 1.15-10.02; p = 0.03). Among those with echocardiography performed later, MC was still associated with higher risk of abnormalities (OR=6.0, 95% CI 1.03-34.94; p = 0.046). A higher frequency of cardiac defects was noted in ZIKV-exposed infants than the general population. Most defects resolved on follow-up. The presence of a congenital heart defect (CHD) could be considered a parameter of CZS given its association with MC.

DiGeorge syndrome (DGS; OMIM #188400), also known as 22q11.2 deletion syndrome, is characterized by cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, and hypocalcemia. The syndrome is ranked as the second most common chromosomal change after Down’s syndrome, accounting for 1 in 2000 newborns. DGS syndrome is typically diagnosed through CGH and/or FISH analysis in developed countries. However, in low-resource healthcare settings, diagnosis often relies primarily on clinical manifestations due to limited access to genetic testing. The present study, the first of its kind, seeks to deepen the understanding of both the clinical and genetic aspects of DGS among Sudanese patients by employing FISH analysis as a confirmatory test. Between 2020 and 2023, 19 patients with DGS as a provisional diagnosis were referred to the Elite Center for Genetic Services for genetic testing and counseling. Cytogenetics and chromosomal analysis were performed following standard protocols, complemented by chromosomal FISH analysis using locus-specific TUPLE1 and α-satellite DNA probes. Of the 19 patients, 9 (47.4%) were male, and 10 (52.6%) were female, with ages ranging from 2 months to 3 years, and a mean of 11 ± 8.6 months. The most common presentations were CHD in 13 (68.4%), dysmorphic features in 12 (63.2%), and recurrent respiratory tract infections in 9 (47.4%). The least common presenting complaint was intellectual disability in only 2 (10.5%) patients. The echocardiogram revealed isolated heart defects in 9 (47.4%) patients, and only 4 (21.1%) had combined cardiac anomalies. Laboratory tests showed hypocalcemia in all four neonatal patients (21.1%) with a previous history of neonatal convulsions. Conventional cytogenetic analyses were suggestive but non-conclusive {46,XY,?del(22) and 46,XX,?del(22)} for DGS. The complementary FISH analysis confirmed the diagnosis by detecting the microdeletion in the DGCR of chromosome 22. Our study highlights the late presentation of DGS for genetic diagnoses. This may be due to limited access to genetic testing, late referrals from treating physicians, or the high cost of the tests. A key area for future research is the environmental factors, such as skin bleaching, that may contribute to DGS in Sudan and other African populations.

Abstract Background Surgical correction of congenital cardiac defects in infancy is being increasingly prevalent there is an increasing population of patients reaching adulthood with corrected congenital heart disease. Pregnancy in these patients can be particularly dangerous and risk stratification is key. Complications during pregnancy can still occur, which in the context of corrected congenital cardiac disease may require unique care. Case Summary A 30-year-old patient in her third trimester of pregnancy presented to hospital with acute onset chest pain and shortness of breath. She had a background of congenital corrected pulmonary atresia via a Modified Blalock-Thomas-Taussig shunt which required conduit replacements through her adolescence and a ventricular septal defect (VSD) repaired with a dacron patch. Routine echocardiograms and electrocardiograms had been stable through her pregnancy. On this occasion, she rapidly deteriorated on presentation to the emergency department and suffered a 15-minute Ventricular Fibrillation (VF) arrest during which she underwent a peri-mortem C-Section. During her cardiac arrest she developed CPR induced consciousness which led to some distressing recall of her treatment. Overall, this was felt to be scar related VF and she left hospital after a 3-week admission with an implantable cardiac defibrillator. She and her newly born baby suffered no ill effects of this cardiac arrest. Discussion This case highlights the necessity for early recognition, rapid intervention, and multidisciplinary collaboration in managing life-threatening maternal cardiac emergencies.

Myotonic dystrophy type 1 (DM1) is caused by a (CTG)n trinucleotide repeat expansion in the 3'UTR of the DMPK gene. Once expressed, repeat RNA forms toxic hairpins that sequester the MBNL (muscle blind-like) family of splicing factors. This disrupts the tissue alternative splicing landscape, triggering multisystemic manifestations-myotonia, muscle weakness, cardiac contractile defects, arrhythmia, and neurological disturbances. Although impaired mitochondrial function has been reported in the brain, skeletal muscle, and fibroblasts of patients with DM1, they have not been reported in the heart, nor have their contribution to the DM1 cardiac pathogenesis been explored. Here, we probed the bioenergetic profile of DM1-afflicted heart tissues and explored the mechanistic basis of DM1-induced cardiac bioenergetic defects. Using an inducible, heart-specific DM1 mouse model, we performed extracellular flux analyses, measured total ATP and NAD(H) concentrations, and performed immunofluorescence staining and transmission electron microscopy to characterize DM1-induced cardiac bioenergetics and mitochondrial structural defects. We analyzed eCLIP-Seq data to identify mitochondria-related missplicing events, which we validated in human and mouse DM1 heart tissues. Finally, we used antisense oligonucleotides to replicate these events and to test the recapitulation of DM1-like bioenergetic and structural defects in vitro. DM1 induced a multistate decrease in oxygen consumption rate with a corresponding reduction in ATP and NAD(H) concentrations, indicating impaired oxidative phosphorylation in DM1-afflicted mouse hearts. We also found significant cardiac mitochondria fragmentation, which correlated with the missplicing of transcripts encoding mitochondria fission factor (Mff, encodes MFF protein) and dynamin related protein 1 (Dnm1l, encodes DRP1 protein) in DM1-afflicted human and mouse hearts. Antisense oligonucleotides-mediated redirection of Dnm1l alternative splicing reproduced DM1-like impairment in cardiac bioenergetics and mitochondrial dynamics in wild-type HL-1 cardiomyocytes. Together, these findings reveal that expanded (CUG)n RNA toxicity in DM1 disrupts cardiac bioenergetics through the missplicing of critical mitochondrial fission transcripts. These misspliced transcripts represent potential therapeutic targets for improving mitochondrial function and cardiac symptoms of DM1.

AhR/ROS-mediated endoplasmic reticulum stress contributes to PFOSA-induced cardiac defects.

Abstract Background: Lethal fetal anomalies are a major contributor to stillbirth and present significant diagnostic and counseling challenges, particularly when multiple organ systems are involved. While chromosomal abnormalities are commonly implicated, monogenic disorders are increasingly recognized as underlying causes. Aim: To evaluates the spectrum of fetal malformations associated with single-gene disorders in patients with a history of stillbirth. Methods: We conducted a retrospective analysis of 269 pregnant patients with prior stillbirths who presented during a subsequent pregnancy over a 3-year period. All underwent detailed ultrasonography, revealing fetal malformations in 84 cases. Results: Invasive prenatal testing was offered to all 84; 73 patients accepted, and 11 declined. Among the 73 tested,23 cases (31.5%) were diagnosed with single-gene disorders,9(12%) cases had chromosomal abnormalities,41(56%) cases showed no identifiable genetic abnormality. Of the 23 monogenic cases, 16 had a history of recurrent stillbirth, and 7 had non-recurrent events. The affected fetuses exhibited diverse anomalies, including renal malformations, skeletal dysplasias, non-immune hydrops fetalis, and cardiac defects. Parental genetic testing confirmed inheritance patterns and facilitated recurrence risk assessment. Conclusion: Monogenic disorders are the hidden culprits behind many lethal fetal anomalies—often overlooked, yet profoundly recurrent. By pairing high-resolution prenatal imaging with precision genetic diagnostics, we unlock the potential to transform uncertainty into clarity. Early detection not only empowers families with answers but also reshapes the trajectory of future pregnancies. It’s time to bring monogenic disorders to the forefront of stillbirth prevention and redefine how we counsel, care, and prepare.

Emery-Dreifuss muscular dystrophy is a rare inherited neuromuscular disorder characterised by early joint contractures, slowly progressive humero-peroneal weakness and cardiac conduction defects or cardiomyopathy. Although contractures and weakness usually begin in childhood, cardiac complications, such as atrioventricular block, arrhythmias and dilated cardiomyopathy, typically emerge in early adulthood and may cause sudden cardiac death, if unrecognised. Anaesthetic management is challenging due to potential airway complications from cervical contractures, restrictive respiratory physiology and cardiac instability. Pre-operative cardiac and pulmonary assessment is essential. Depolarising neuromuscular blocking agents and volatile anaesthetics are not absolutely contraindicated but are preferably avoided due to the risk of rhabdomyolysis or malignant hyperthermia-like reactions. Total intravenous anaesthesia is preferred to minimise these risks. We report a 27-year-old man with genetically confirmed Emery-Dreifuss muscular dystrophy and severe multisystem involvement who underwent cardiac resynchronisation therapy pacemaker implantation under total intravenous anaesthetic technique with rocuronium and reversal with sugammadex. Anaesthetic management focused on malignant hyperthermia precautions, airway preparation for limited cervical mobility and minimising arrhythmia risk with readiness for external cardiac pacing. The procedure and recovery were uneventful, demonstrating that the total intravenous anaesthetic technique can be an effective technique for patients with Emery-Dreifuss muscular dystrophy undergoing device implantation.

Assess prenatal ultrasound's diagnostic value in fetal cardiac anomalies using an abnormal number of pulmonary artery (PA) branches as an initial clue. Retrospective analysis of 20 fetuses with an abnormal number of PA branches on ultrasound, comparing prenatal ultrasonic findings with postnatal echocardiography, computed tomography (CT), surgery, autopsy, and genetic tests. Summarized ultrasonographic characteristics and occurrence frequencies in 3-vessel trachea (3VT), 3-vessel PA branch, and innominate artery (INA) coronary section. In total, abnormal PA branches included: 1 branch (15 cases: 7 pulmonary artery sling [PAS], 4 unilateral absence of pulmonary artery [UAPA], 4 anomalous origin of 1 pulmonary artery from ascending aorta [AOPA]); 3 branches (2 cases: 1 isolated left subclavian artery [ILSA], 1 isolated left innominate artery [ILINA], absent right ductus arteriosus); 4 branches (3 cases: 2 ILSA, 1 ILINA, double ductus arteriosus). Associated anomalies: tetralogy of Fallot, persistent left superior vena cava, ventricular septal defect, Berry syndrome, and nasal bone dysplasia. Postnatal confirmations were achieved via autopsy (9 cases), imaging/surgery (10 cases), or lost (1 case). Genetic tests (14 cases) were normal. Detection: 63.2% (3VT section), 100% (3-vessel PA branch section), 57.9% (INA coronary section). The 3VT, 3-vessel PA branch, and INA coronary section are key for the diagnosis of fetal cardiac malformations with abnormal PA branches. The spatiotemporal image correlation with high-definition (STIC-HD) live flow sonography can aid in visualizing the vascular connection linked to these anomalies. Identifying features of 1/3/4 PA branches facilitates a systematic assessment of fetal cardiac defects primarily characterized by aberrant PA branching.

Background: Turner syndrome (TS) is a chromosomal disorder associated with considerable phenotypic variability and lifelong multisystem comorbidities. Beyond somatic manifestations, TS may substantially affect physical, psychological, and social functioning, highlighting the need for comprehensive assessment of quality of life in affected women. Methods: This observational comparative study included 30 adult women with genetically confirmed Turner syndrome and 43 age-matched healthy controls. Quality of life was assessed using the SF-36 questionnaire, with clinical, anthropometric, and psychosocial variables analyzed as potential predictors using correlation and multivariable regression analyses. Results: Women with Turner syndrome were significantly shorter than controls and more frequently affected by hypothyroidism, cardiac defects, and hearing impairment. They scored lower on SF-36 domains of general health, vitality, social functioning, and mental health, while exhibiting higher BDI-II depressive symptoms. Quality of life correlated negatively with comorbidity burden and depressive symptoms, positively with final height, and was lower in patients with hearing impairment, highlighting the multifactorial determinants of well-being in TS. Conclusions: Health-related quality of life in women with Turner syndrome is shaped by a complex interplay of somatic burden, psychological well-being, and social functioning. Depressive symptoms, comorbidities, stature, and hearing impairment significantly influence outcomes, emphasizing the need for holistic, multidisciplinary care that extends beyond medical management.

Sagittal craniosynostosis, the most common nonsyndromic form, typically causes scaphocephaly and occurs more often in males. This report describes a 2-month-old boy with sagittal craniosynostosis associated with a rare chromosome 16p13.3 duplication, detected by chromosomal microarray analysis despite a normal karyotype. He had dysmorphic facies, cardiac defects, and undescended testes. At 23 months, he underwent cranial vault remodeling with marked improvement; follow-up showed a normal head shape but mild developmental delay. This case underscores the value of chromosomal microarray in diagnosing syndromic craniosynostosis and highlights the need for multidisciplinary care. It represents a previously unrecognised association between chromosome 16p13.3 duplication and craniosynostosis.

Introduction and objective: Edwards Syndrome, also known as Trisomy 18, is the second most common autosomal trisomy following Down Syndrome. This chromosomal disorder is characterized by the presence of a third copy of chromosome 18, in contrast to the usual two. The condition is associated with a wide spectrum of severe congenital anomalies, significant developmental delays, and a high rate of fetal loss and infant mortality. Therefore, a comprehensive synthesis of these associated developmental anomalies is crucial for accurate prenatal counseling, clinical guidance, and postnatal management. The primary objective of this comprehensive review is to systematically identify, collate, and synthesize the existing literature regarding the range and prevalence of congenital heart defects in children diagnosed with Edwards Syndrome. Recognizing that cardiac anomalies are a cardinal feature and a leading cause of mortality in this condition, this review aims to provide a detailed, evidence-based overview of these specific manifestations. Ultimately, this focused analysis seeks to enhance clinical understanding of the cardiovascular complications in Edwards Syndrome and inform targeted management strategies. Brief description of the state of knowledge: Edwards Syndrome (Trisomy 18) is characterized by a high burden of congenital anomalies, with cardiac defects affecting the vast majority of patients and serving as a primary determinant of survival. Historically regarded as a uniformly lethal condition requiring only palliative care, the clinical perspective is evolving. Recent data indicate that cardiac interventions may offer survival benefits, challenging traditional non-interventional paradigms and necessitating an updated understanding of the cardiovascular phenotype. Methods: A systematic literature review was performed by searching major biomedical databases (PubMed, Google Scholar, Elicit) using a combination of keywords and MeSH terms, including "Edwards Syndrome" and "congenital abnormalities." Inclusion criteria prioritized peer-reviewed articles such as case series, observational studies, and systematic reviews. Data extraction focused on the types, frequency, and systemic impact of anomalies, as well as postnatal developmental outcomes. The collected data were then synthesized to create a comprehensive syndrome profile. Conclusions: The clinical paradigm for Edwards Syndrome is shifting from a uniform designation of lethality toward a personalized, multidisciplinary model. Accurate prenatal diagnosis via fetal echocardiography is essential for early risk stratification. Contemporary management requires a balanced approach integrating palliative care with the option of active cardiac intervention. Consequently, parental counseling must emphasize shared decision-making, providing families with evidence-based data on potential surgical outcomes to optimize the quality of life for the affected child.

Background: Monozygotic twin pregnancies are at increased risk of congenital abnormalities compared to singletons. In 20% of cases, both fetuses are affected (concordance), while in 80% of cases, only one fetus is affected (discordance). This study examines the prevalence of discordance for structural defects in monochorionic (MC) twins, with normal aCGH comparative genomic hybridization (aCGH), reporting the types of detected abnormalities and their possible impact on perinatal outcomes, including the rate of single and double fetal loss before 24 weeks’ gestation and the rate of preterm birth (PB) before 32 weeks’ gestation. Methods: This was a retrospective study of discordant structural fetal anomalies in MC twin pregnancies detected at first-trimester scanning in three fetal medicine centers in Poland. Results: In the study population of 381 monochorionic twin pregnancies examined at 11–13 weeks’ gestation, 21 (5.5%) pregnancies showed discordant structural defects with normal aCGH result. The most common were cardiac defects (n = 8), followed by central nervous system (CNS) (n = 6) defects and facial anomalies (n = 3). Single or double fetal loss before 28 weeks occurred in four (19%) and two (9%) cases, respectively, and was associated with intertwin crown–rump length (CRL) discordance greater than 20% (p = 0.046). PB before 32 weeks’ gestation occurred in nine cases (47%) and was strongly associated with polyhydramnios (p = 0.001), which occurred mainly in CNS and facial defects. Conclusions: The prevalence of discordant structural defects with normal aCGH results among monochorionic twins is approximately 5%. In pregnancies with discordant defects, cardiac defects are the most common. Intertwin discordance greater than than 20% is associated with an increased risk of fetal demise.

Percutaneous device closure is the preferred method for closing patent ductus arteriosus (PDA), even in preterm infants. We report our experience using the new KONAR-MFO™ ventricular septal defect occluder for transcatheter closure of preterm patent ductus arteriosus as an alternative device in resource-limited centres. Case 1: A preterm baby with Down'ssyndrome and tracheobronchomalacia was born at 29 weeks, weighing 1.68 kg with multiple cardiac defects, including a 4 mm PDA and a 6 mm mid-muscular ventricular septal defect (VSD), stuck on a ventilator. Case 2: Another preterm baby born at 35 weeks, weighing 1.89 kg,with anorectal malformation and a right inguinal hernia. The echocardiogram revealed a 4 mm PDA with severe PAH. In both cases, the patent ductus arteriosus was occluded using a 6 mm × 4 mm Konar MFO device on day 14 (case 1) and day 20 (case 2). The baby (case 1) was weaned off the ventilator and discharged on the 28th postnatal day at 2.09 kg. As for case 2, the baby was weaned off the ventilator within 2 days and discharged on day 30 at 2.23 kg. A follow-up echocardiogram of both cases confirmed a well-positioned device with no obstructions. At 18 months, in the follow-up, both babies were gaining weight and thriving. The KONAR MFO device is a safe and effective option for patent ductus arteriosus closure in preterm infants, even in resource-limited settings. Its versatility accommodates various duct sizes and morphologies, and its self-expandable design ensures easy deployment, addressing the anatomical challenges often seen in preterm infants.

Aberrant right subclavian artery is a common anatomical variant of the embryonic aortic arch, with a prevalence ranging from 0.4 to 2.0%. Although frequently associated with vascular rings or congenital cardiac defects, prenatal assessment primarily relies on the three-vessel and trachea view in ultrasonography. Currently, there is no consensus regarding whether isolated ARSA necessitates invasive diagnostic procedures. This study aimed to evaluate the necessity of routine invasive prenatal diagnosis for fetuses with sonographically isolated ARSA. By conducting a long-term postnatal follow-up of a large cohort and utilizing Bayesian analysis for risk assessment, we sought to provide empirical data to support clinical decision-making. The fetuses diagnosed with ARSA via prenatal ultrasound at Hefei Maternal and Child Health Care Hospital from January 2019 to December 2022 were retrospectively analyzed. They were divided into isolated ARSA and non-isolated ARSA groups based on the presence or absence of other ultrasound abnormalities. Within each of these two groups, the fetuses were further categorized into diagnostic and undiagnosed subgroups based on whether they underwent invasive prenatal diagnosis. The study explored the baseline characteristics, genetic testing results, pregnancy outcomes, infant feeding and developmental status, and the results of neonatal color Doppler ultrasound re-examinations in these two groups. A total of 540 cases of ARSA fetuses were identified, including 449 cases (83.1%) of isolated ARSA and 91 cases (16.9%) of non-isolated ARSA. There were no statistically significant differences in baseline characteristics such as age, pre-pregnancy BMI, and history of diabetes between the two groups (P > 0.05). However, the proportion of non-invasive prenatal testing (NIPT) applications and the pregnancy termination rate were significantly higher in the non-isolated group compared to the isolated group (P < 0.05). Pregnancy outcomes revealed that there were 496 live births (91.6%), while 44 cases (8.1%) chose to terminate their pregnancies due to chromosomal abnormalities and/or severe structural abnormalities. Among the 90 fetuses that underwent invasive prenatal diagnosis, the overall detection rate of chromosomal abnormalities was 11.1%. The detection rates for isolated and non-isolated ARSA were 9.1% (6/66) and 16.7% (4/24), respectively, with no statistically significant difference between the two groups (P > 0.05).The follow-up results of live births showed that 25 (5.0%) of 496 cases had abnormal phenotypes. Among 446 live births with isolated ARSA, 10 cases (2.2%) were found to have abnormal manifestations, with 1.6% (1/66 cases, diagnosed as 21-trisomy mosaicism) in the invasive diagnosis group and 2.4% (9/380 cases) in the undiagnosed group. The difference between the two groups was not statistically significant (P > 0.05). In contrast, the abnormal phenotype rate of live births with non-isolated ARSA was nearly 30.0%. Bayesian risk assessment indicated that the overall posterior risk of abnormal phenotype for isolated ARSA was 2.46% (95% HDI: 1.195%-4.080%), and whether or not invasive diagnosis was performed did not alter this risk. Among the 407 live births that did not undergo invasive diagnosis, 17 cases (4.2%) exhibited abnormalities during follow-up, among whom, genetic testing identified pathogenic variants in two neonates. The positive predictive value for postnatal aberrant clinical symptoms in fetuses with sonographically isolated ARSA is low (2.24%). In the absence of additional ultrasound markers or significant risk factors, routine invasive prenatal diagnosis is not recommended. Comprehensive genetic counseling should be prioritized to facilitate informed and autonomous decision-making by pregnant women and their families.

Background: Congenital cardiac malformations constitute one of the leading causes of perinatal morbidity and mortality, accounting for nearly one-third of all major structural fetal anomalies. Despite advances in prenatal imaging, particularly fetal echocardiography, accurate delineation of complex cardiac defects often remains challenging. Autopsy studies continue to play a pivotal role in confirming prenatal diagnoses, understanding embryopathogenesis, and identifying associated extracardiac abnormalities. Objectives: To study the spectrum and frequency of congenital cardiac malformations in perinatal deaths, assess their gestational and sex distribution, correlate with mode of death and fetal weight, and identify associated extracardiac anomalies. Materials and Methods: A retrospective descriptive study comprising 20 perinatal autopsy cases with major congenital cardiac malformations was conducted over a one-year period. Each case was analyzed for gestational age, sex, estimated birth weight, associated malformations, and mode of death. Statistical analysis included descriptive measures and correlation between gestational age and fetal weight. Results: The mean gestational age was 21.5 weeks and mean fetal weight was 447 g. Males constituted 65%, females 30%, and 5% had ambiguous genitalia (M: F = 2.1:1). The predominant mode of death was therapeutic termination (60%), followed by spontaneous abortion (30%) and intrauterine death (10%). The most frequent cardiac malformations were Double Outlet Right Ventricle (DORV) and Hypoplastic Left or Right Heart Syndromes, often associated with Congenital Cystic Adenomatoid Malformation (CCAM) or chromosomal syndromes such as Down and Mermaid Syndrome. A strong positive correlation (r = 0.95) was observed between gestational age and fetal weight. Conclusion: Perinatal autopsy remains a cornerstone for confirming and characterizing congenital cardiac malformations. Comprehensive autopsy evaluation enhances the understanding of associated extracardiac defects and aids in accurate genetic counseling, thereby contributing significantly to perinatal care and prevention strategies.

The heart's atria and ventricles have different functions and developmental origins, and common cardiac defects have specific effects on each chamber. However, the gene regulatory networks (GRN) that govern their specification - and how this goes awry in genetic heart diseases - remain unclear. In a new study, Irfan Kathiriya, Benoit Bruneau and colleagues address these outstanding questions by using epigenomic analyses to define the GRN of atrial and ventricular cardiomyocytes derived from human induced pluripotent stem cells. In doing so, they identify TBX5 as a key regulator of the GRN governing atrial cell type specification and a potential therapeutic target for genetic atrial diseases. To learn more about this study and the people behind it, we talked to corresponding author Benoit Bruneau, and both first and corresponding author Irfan Kathiriya, Professor of Anesthesia at the University of California, San Francisco, USA.

To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.

Genomic copy number variations, such as the 22q11.2 microdeletion syndrome, cause pleiotropic disorders that affect diverse organ systems and disrupt neurodevelopment. Deletions of the 22q11.2 locus reduce the dosage of up to 46 protein coding genes, raising questions about the identity of haploinsufficient genes and their genetic interactions contributing to 22q11.2 phenotypes. Here, we dissect functional and molecular relationships between two genes encoded within the 22q11.2 locus: the mitochondrial ribosomal protein gene MRPL40 and the mitochondrial citrate transporter SLC25A1. We show that a MRPL40 null mutation disrupts mitochondrial translation, impairs respiration, and affects multiple components of the SLC25A1 interactome including factors required for lipid metabolism, mitochondrial ribosome subunits, and the mitochondrial RNA processing machinery. In silico coessentiality network analysis revealed correlated and anticorrelated fitness interactions linking MRPL40 and SLC25A1 to mitochondrial translation, intermediate carbon metabolism, and interferon signaling. We determined that Mrpl40-null mutations are embryonic lethal in mice, but Mrpl40−/+ mice are viable and displayed embryonic cardiac development and adult behavioral phenotypes. Similarly, Slc25a1+/− animals showed embryonic cardiac developmental defects but lacked the adult behavioral phenotypes observed in Mrpl40−/+ mice. Surprisingly, transheterozygotic Slc25a1+/−;Mrpl40−/+ mice suppressed or mitigated cardiac development, behavioral, and brain transcriptome phenotypes observed in single heterozygotic animals. These results reveal that MRPL40 and SLC25A1 are haploinsufficient genes within the 22q11.2 locus that genetically and biochemically interact to define tissue development and physiology. Our findings provide a framework for understanding the complexity and type of gene dosage interactions within the 22q11.2 deletion syndrome locus.

Resveratrol attenuates trimethyltin chloride-induced cardiac defects via the ROS/Wnt/β-catenin pathway.

Early-life exposure to flusilazole causes transgenerational cardiac developmental defects in zebrafish and its potential causes