Persistent Truncus Arteriosus Research Articles

A novel MED12 pathogenic variant in a female fetus with facial cleft and cardiac defects identified in the first trimester.

Trio exome sequencing was performed on a female fetus with an increased nuchal translucency, along with nasal bone hypoplasia, suspected cleft palate and abnormal outflow tract of the heart. A de novo heterozygous variant c.5500_5507del, p.(Tyr1834Argfs × 58) in the MED12 gene was detected. Loss-of-function variants in MED12 in females are associated with Hardikar syndrome (HS). A follow-up ultrasound at 15+5weeks of gestation identified multiple fetal anomalies including bilateral cleft lip and palate, diaphragmatic hernia, atrioventricular septal defect, persistent truncus arteriosus, and bilateral renal pelvis dilation. Fetal autopsy confirmed the prenatal sonographic findings, and the MED12 variant was discussed by our multidisciplinary team to be the cause of fetal anomalies. Our case is the first prenatal one in which HS was diagnosed due to first trimester structural malformations. This case report presents another example of early identification of a major anomaly which allows earlier genetic diagnosis and more time for clinical management.

Relationship between diagnosis of conus arteriosus malformation and genetic diagnosis results in fetal cardiac axis abnormalities by echocardiography during middle pregnancy

ObjectiveTo explore the clinical value of echocardiography in detecting fetal cardiac axis abnormalities during middle pregnancy for diagnosing conus arteriosus malformation, and to compare and analyze the genetic diagnosis results, in order to provide evidence for clinical diagnosis and intervention.MethodsFour hundred twenty-one fetuses with conus arteriosus malformation from January 2020 to October 2023 were included as the conus arteriosus malformation group, and 917 healthy fetuses (all single fetuses) matched at the same gestational age were selected as the healthy group.ResultsThere was no significant difference in gestational weeks between two groups (P > 0.05). The age of pregnant women in conus arteriosus malformation group was lower compared to healthy group (P < 0.05), and the fetal cardiac axis in conus arteriosus malformation group was significantly higher compared to healthy group (P < 0.05). Among the fetuses with conus arteriosus malformation, tetralogy of Fallot (TOF), transposition of the great arteries (TGA) and double outlet right ventricle (DORV) had the highest proportions, accounting for 38.00%, 18.29% and 17.58%, respectively. Among all types of conus arteriosus malformations, atresia pulmonary valve syndrome associated with TOF, persistent truncus arteriosus and DORV exhibited higher proportions of fetal cardiac axis abnormalities, at 75.00%, 36.84% and 27.03%, respectively, while TGA and interrupted aortic arch associated with B-type interruption had lower proportions of fetal cardiac axis abnormalities, at 2.60% and 4.55%, respectively. Genetic testing was conducted on 73 cases (17.34%) of fetuses with conus arteriosus malformation in this study. Among them, fetal cardiac axis abnormalities were considered positive for genetic results due to factors such as aneuploidy, copy number abnormalities, and single-gene pathogenicity. A total of 31 cases tested positive for genetic anomalies, with a positive rate of approximately 42.47%.ConclusionIn the middle pregnancy, the fetal cardiac axis in cases of conus arteriosus malformation was significantly higher than in normal fetuses. Moreover, there were variations in fetal cardiac axis among different types of conus arteriosus malformations, and these differences were notably associated with genetic diagnostic results.

The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del of TMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most well-known genetic cause of PTA. Phenotype of patients with c.1617del appears to be predominantly in the heart, although TMEM260 is responsible for structural heart defects and renal anomalies syndrome (SHDRA). The mouse TMEM260 variant (p.W535Cfs*56), synonymous with the human variant (p.W539Cfs*9), exhibited truncation and downregulation by western blotting, and aggregation by immunocytochemistry. In situ hybridization demonstrated that Tmem260 is expressed ubiquitously during embryogenesis, including in the development of cardiac OFT implicated in PTA. This expression may be regulated by a ~ 0.8 kb genomic region in intron 3 of Tmem260 that includes multiple highly conserved binding sites for essential cardiac transcription factors, thus revealing that the c.1617del variant of TMEM260 is the major single-gene variant responsible for PTA in the Japanese population.

Partial Heart Transplant in a Neonate With Irreparable Truncal Valve Dysfunction

The treatment of neonates with irreparable heart valve dysfunction remains an unsolved problem because there are no heart valve implants that grow. Therefore, neonates with heart valve implants are committed to recurrent implant exchanges until an adult-sized valve can fit. To deliver the first heart valve implant that grows. Case report from a pediatric referral center, with follow-up for more than 1 year. Participants were a recipient neonate with persistent truncus arteriosus and irreparable truncal valve dysfunction and a donor neonate with hypoxic-ischemic brain injury. First-in-human transplant of the part of the heart containing the aortic and pulmonary valves. Transplanted valve growth and hemodynamic function. Echocardiography demonstrated adaptive growth and excellent hemodynamic function of the partial heart transplant valves. In this child, partial heart transplant delivered growing heart valve implants with a good outcome at age 1 year. Partial heart transplants may improve the treatment of neonates with irreparable heart valve dysfunction.

Dgcr8 functions in the secondary heart field for outflow tract and right ventricle development in mammals

The DGCR8 gene, encoding a critical miRNA processing protein, maps within the hemizygous region in patients with 22q11.2 deletion syndrome. Most patients have malformations of the cardiac outflow tract that is derived in part from the anterior second heart field (aSHF) mesoderm. To understand the function of Dgcr8 in the aSHF, we inactivated it in mice using Mef2c-AHF-Cre. Inactivation resulted in a fully penetrant persistent truncus arteriosus and a hypoplastic right ventricle leading to lethality by E14.5. To understand the molecular mechanism for this phenotype, we performed gene expression profiling of the aSHF and the cardiac outflow tract with right ventricle in conditional null versus normal mouse littermates at stage E9.5 prior to morphology changes. We identified dysregulation of mRNA gene expression, of which some are relevant to cardiogenesis. Many pri-miRNA genes were strongly increased in expression in mutant embryos along with reduced expression of mature miRNA genes. We further examined the individual, mature miRNAs that were decreased in expression along with pri-miRNAs that were accumulated that could be direct effects due to loss of Dgcr8. Among these genes, were miR-1a, miR-133a, miR-134, miR143 and miR145a, which have known functions in heart development. These early mRNA and miRNA changes may in part, explain the first steps that lead to the resulting phenotype in Dgcr8 aSHF conditional mutant embryos.

20-Year follow-up and comparison of valved conduits used for right ventricular outflow tract reconstruction: single-centre, propensity score match analysis.

Surgical repair of complex congenital heart defects with hypoplasia or atresia of the right ventricular outflow tract (RVOT) may require pulmonary valve implantation or replacement during the primary repair or reoperation. The purpose of this study is to evaluate the outcomes of cryopreserved homografts, bovine jugular vein conduits and decellularized Matrix P Plus N conduits in patients undergoing RVOT reconstruction at a single centre. Retrospective, single-centre review of 173 patients with 199 conduits undergoing right ventricle-to-pulmonary artery reconstruction with valved conduit from 2002 to 2022. A total of 199 conduits were implanted in 173 patients (62.8% male), with a mean age of 8.97 ± 8.5 years. The following 3 types of conduits were used: homografts 129 (64.8%), bovine jugular vein conduits 45 (22.7%) and Matrix P Plus N 25 (12.5%). During the mean follow-up duration of 8.6 ± 5.8 years, there were 20 deaths, 35 conduit reoperations and 44 catheter reinterventions. Overall survival, reoperation-free and catheter reintervention-free survival at 20 years were 83%, 67.8% and 65.6%, respectively. Multivariable Cox analysis identified younger patient age, smaller conduit size, low patient weight and primary diagnosis of common arterial trunk as risk factors for reoperation and catheter reintervention. Long-term outcomes of reconstruction of the RVOT using homografts, bovine jugular vein and Matrix P Plus N conduits were acceptable. The reoperation rate for conduit dysfunction did not differ significantly among groups. Over time, the need for conduit replacement was higher in smaller conduits and in patients with common arterial trunk diagnosis.

Echocardiography: conotruncal anomaly: a case of common arterial trunk with intact ventricular septum and hypoplastic left heart complex with unbalanced pulmonary stenoses.

We describe the echocardiographic findings of a common arterial trunk with intact ventricular septum, mitral and left ventricular hypoplasia, atretic left ventricular outlet and bilateral, and unbalanced pulmonary artery stenoses.

Pulmonary Atresia (PA) with Anomalous Origin of the Pulmonary Artery

Pulmonary atresia with ventricular septal defect is a severe form of congenital cyanotic heart disease (TOF) but its not very common form. Here main pulmonary does not arises from common arterial trunk. In pulmonary atresia there is no proper formation ofthe pulmonary valve which allows blood from the heart to thelung of patient. Instead of opening and closing of the valve,a solid sheet of tissue develops. Therefore blood cannot flow by its normal path to take oxygen from the lung. Instead, inadequate blood travels to the lung through other natural routes within the heart and its arteries and presenting degree of pulmonary atresia or discontinuity in arteries. MDCT gave structural details in this regard. So, role of MDCT play an important role to evaluate the details important information needed in preoperative evaluation for surgical policy in atretic patients. Here we discuss a case of pulmonary atresia (PA) with anomalous origin of the pulmonary artery.KYAMC Journal Vol. 14, No. 02, July 2023: 102-104.

Energy device injury. Common basilar arterial trunk injury with harmonic scalpel.

Energy device injury. Common basilar arterial trunk injury with harmonic scalpel.

EP24.45: Common arterial trunk type 1 (by Collett and Edwards) – type A1 (by Van Praagh and Van Praagh) at 22 weeks

EP24.45: Common arterial trunk type 1 (by Collett and Edwards) – type A1 (by Van Praagh and Van Praagh) at 22 weeks

Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis.

Pathogenic GATA6 variants have been associated with congenital heart disease (CHD) and a spectrum of extracardiac abnormalities, including pancreatic agenesis, congenital diaphragmatic hernia, and developmental delay. However, the comprehensive genotype-phenotype correlation of pathogenic GATA6 variation in humans remains to be fully understood. Exome sequencing was performed in a family where four members had CHD. In vitro functional analysis of the GATA6 variant was performed using immunofluorescence, western blot, and dual-luciferase reporter assay. A novel, heterozygous missense variant in GATA6 (c.1403 G > A; p.Cys468Tyr) segregated with affected members in a family with CHD, including three with persistent truncus arteriosus. In addition, one member had childhood onset diabetes mellitus (DM), and another had necrotizing enterocolitis (NEC) with intestinal perforation. The p.Cys468Tyr variant was located in the c-terminal zinc finger domain encoded by exon 4. The mutant protein demonstrated an abnormal nuclear localization pattern with protein aggregation and decreased transcriptional activity. We report a novel, familial GATA6 likely pathogenic variant associated with CHD, DM, and NEC with intestinal perforation. These findings expand the phenotypic spectrum of pathologic GATA6 variation to include intestinal abnormalities. Exome sequencing identified a novel heterozygous GATA6 variant (p.Cys468Tyr) that segregated in a family with CHD including persistent truncus arteriosus, atrial septal defects and bicuspid aortic valve. Additionally, affected members displayed extracardiac findings including childhood-onset diabetes mellitus, and uniquely, necrotizing enterocolitis with intestinal perforation in the first four days of life. In vitro functional assays demonstrated that GATA6 p.Cys468Tyr variant leads to cellular localization defects and decreased transactivation activity. This work supports the importance of GATA6 as a causative gene for CHD and expands the phenotypic spectrum of pathogenic GATA6 variation, highlighting neonatal intestinal perforation as a novel extracardiac phenotype.

Common arterial trunk repair after infancy.

Common arterial trunk repair after infancy.

Criss-cross pulmonary arteries in common arterial trunk – Implications to management and outcome

ObjectivesTo investigate the incidence, types and pathophysiology of criss-cross pattern of the proximal pulmonary arteries in common arterial trunk and its influence on management and outcomes. MethodsRetrospective review of all patients with common arterial trunk who underwent Aswan Truncus Operation with regard to the origin and course of the proximal pulmonary artery branches as defined by 3D segmented models pre, immediately and 1 and 2 years after operation. ResultsBetween January 2019 and September 2022, 39 patients (19 males, aged 1–12 months) underwent the Aswan Truncus Operation. 18 patients (46%) had criss-cross arrangement of the proximal pulmonary artery. The mortality, ICU and hospital stay were not affected by the presence or absence of the criss-cross pattern. However, following operation in the criss-cross group, there was evidence of different degrees of kinking and twisting of the right pulmonary artery. This resulted in severe narrowing which required stenting or reoperation at different stages (1 during ICU stay and another after 1 year). Separate origin of the left pulmonary artery (Criss-cross Type 2) from a long stenotic ductus arteriosus required resection of the stenotic segment followed by anastomosis to the right pulmonary artery recreating a 60° angle of bifurcation. ConclusionCriss-cross pattern of proximal pulmonary arteries is common in patients with common arterial trunk. Pre-operative diagnosis and tailored approaches of repair are required to prevent late complications.

Surgical outcomes of common arterial trunk repair beyond infancy.

The aim of this study is to analyze the clinical outcomes of common arterial trunk repair beyond infancy in terms of both early- and long-term outcomes. Between January 2003 and December 2019, 56 patients underwent repair for common arterial trunk beyond infancy at our institute. Median age was 34.5months, 51.8% were females, and 48.2% were males. 48.2% were type 1, 46.4% were type 2, and 5.4% were type 3. 17.9% patients underwent direct connection technique for right ventricular outflow tract reconstruction; remaining received a conduit. The most common type of truncal valve anatomy was tricuspid (82.1%). Early mortality was 7%. Univariable analysis identified age (p = 0.003), weight (p = 0.04), duration of ventilation (p = 0.036), and pulmonary hypertensive crisis (p ≤ 0.001) as factors affecting early mortality. In our overall cohort of beyond infancy repair for common arterial trunk, at 10years, the survival, freedom from reintervention for right ventricular outflow tract reconstruction, freedom from ≥ moderate conduit obstruction, freedom from impaired right ventricle function, and freedom from ≥ moderate truncal valve regurgitation were 76.7%, 89.7%, 74%, 88.6%, and 66.3%, respectively. Repair for common arterial trunk in patients presenting beyond 1year of age is challenging; however, it can be done with satisfactory early and late outcomes in terms of mortality and reintervention.

PR and QRS interval changes after transcatheter pulmonary valve replacement in children

BackgroundChanges in PR intervals after transcatheter pulmonary valve replacement (TCPVR) have not been thoroughly evaluated in children. This study evaluated the changes in PR and QRS intervals six months after TCPVR in children with congenital heart disease.ResultsThis study included 41 patients who underwent TCPVR from 2010 to 2022. ECG of patients was reviewed before and six months after TCPVR, and the PR and QRS intervals were reported. Right ventricular systolic pressure (RVSP) was retrieved indirectly from echocardiography and compared pre- and 6-months after TPVR. The median age was 13 years (25th–75th percentiles: 11–16), and 61% were males. The preoperative diagnosis was tetralogy of Fallot (n = 29, 71%), transposition of great vessels (n = 4, 10%), common arterial trunk (n = 3, 7%), pulmonary valve stenosis (n = 3, 7%) and pulmonary atresia (n = 2, 5%). The Melody valve was used in 30 patients, and Edwards Sapien was used in 11 patients. RVSP was significantly reduced six months after the procedure (pre-RVSP 40 (30–55) mmHg vs. post-RVSP 25 (20–35) mmHg; P < 0.001). The PR interval was 142 (132–174) msec before TPVR and 146 (132–168) msec post-TCPVR (P = 0.442). Post-TPVR PR was positively related to the pre-PR (β: 0.79 (0.66–0.93), P < 0.001) and inversely related to the right ventricular outflow tract size (− 1.48 (− 2.76 to − 0.21), P = 0.023). The pre-TPVR QRS was 130 (102–146) msec, and the post-TPVR QRS was 136 (106–144) msec (P = 0.668).ConclusionsIn children undergoing TCPVR, the PR and QRS intervals did not change significantly during a 6-month follow-up.

Novel frameshift mutations in SALL4 in two Chinese families with Okihiro syndrome

In the present study, clinical manifestations of two Chinese Okihiro syndrome families were analyzed, and genetic detections were performed on the two probands by exome sequencing and verified by Sanger sequencing for family members to determine the biological pathogenesis. Prenatal diagnoses were provided for three high-risk fetuses. The affected members exhibited a wildly spectrum of phenotypes, including ultrasound abnormalities of skeletal system (radius deformity and abnormal posture), and cardiac system (persistent common arterial trunk and ventricular septal defect) in the prenatal period of family 1, the severe phenotypes (grossly shortened and deformed forearm, Duane's anomaly and hearing loss), and the mild ones (usually only thenar dysplasia, or short radius styloid process). Two SALL4 variants, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), have been identified respectively in two probands, and c.2210delG of SALL4 gene was unreported previously. The two variants were verified in all affected individuals, not in normal family members. Genotyping results of three fetuses indicated that one fetus was normal, and the two fetuses with heterozygous variation were affected. The two variants of SALL4 gene, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), were the molecular pathological cause of Okihiro syndrome in the present study and enriched the spectrum of SALL4 variants. Our study provides accurate prenatal genetic diagnosis for the two families to avoid the birth of affected children.

Clinical value of prenatal ultrasound in diagnosis and classification of common arterial trunk.

To investigate the clinical value of prenatal ultrasound in the diagnosis of the common arterial trunk (CAT) classification and associated malformations. The 2D ultrasound images, spatiotemporal image correlations (STICs) and clinical data of 88 fetuses diagnosed with CAT malformations by prenatal ultrasound were retrospectively analyzed and classified. The correlation between different types, fetal malformation and pregnancy outcomes were analyzed. Among the 88 fetuses, there were 39 cases (44.32%) of type A1, 40 cases (45.45%) of type A2, 8 cases (9.09%) of type A3, and 1 case of type A4 (1.14%). There were 16 cases (18.18%) with isolated CAT, 48 cases (54.55%) with complex intra-cardiac structural abnormalities, and 24 cases (27.27%) with intra-cardiac and extra-cardiac structural abnormalities. In extra-cardiac structural malformations, 14 cases were associated with 1 other system abnormality, 4 cases with 2 other system abnormalities, 3 cases with 3 other system abnormalities, while 3 cases were combined with 4 other system abnormalities, among which the facial and physical abnormalities had the highest incidence (39.13%). The STIC images were completely displayed in all 88 cases. There was a statistical difference between isolated CAT and CAT combined with other abnormalities in fetal pregnancy outcomes. Prenatal ultrasound had a high clinical application value in CAT classification. Pregnancy outcomes were highly correlated with the classification and associated intra-cardiac and extra-cardiac structural malformations. The early evaluation of fetal prognosis before birth has important value for clinical intervention.

Catheter closure of residual muscular VSD after common arterial trunk repair using Amplatzer muscular occluder (patient number 3 in Table S1). VSD, ventricular septal defect.

Catheter closure of residual muscular VSD after common arterial trunk repair using Amplatzer muscular occluder (patient number 3 in Table S1). VSD, ventricular septal defect.

Common arterial trunk (Van Praagh type A3), absent right pulmonary artery and right aortic arch in a cyanotic child.

A 5-year-old girl with cyanotic congenital heart disease underwent computed tomography which revealed common arterial trunk from both ventricles with origin of the left pulmonary artery from the common trunk and right lung supplied by aorto-pulmonary collaterals with absent pulmonic valve and right pulmonary artery entirely. There was right-sided aortic arch with common origin of the left innominate artery and right common carotid artery.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ISUOG Practice Guidelines (updated): fetal cardiac screening.