JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype

Alagille syndrome (AGS, MIM 118450) is an autosomal dominant disorder with a variable phenotype characterised by hepatic, eye, cardiac, and skeletal malformations and a characteristic facial appearance. Mutations within the gene JAGGED1 (JAG1), which encodes a ligand for NOTCH receptor(s), has been shown to cause Alagille syndrome. Interactions of NOTCH receptors and their ligands influence cell fate decisions in several developmental pathways. We report the tissue expression of JAG1 in human embryos.
We have performed tissue in situ hybridisation on human embryos aged 32-52 days using ³⁵S labelled riboprobes for JAG1. JAG1 is expressed in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, and in the neural tube. We conclude that JAG1 is expressed in the structures affected in Alagille syndrome, such as the pulmonary artery, anterior chamber of the eye, and face.


Keywords: Alagille syndrome; arteriohepatic dysplasia; JAGGED1; NOTCH signalling     

Evaluation of Cardiovascular Anomalies in Patients with Asymptomatic Turner Syndrome Using Multidetector Computed Tomography

Turner syndrome is well known to be associated with significant cardiovascular abnormalities. This paper studied the incidence of cardiovascular abnormalities in asymptomatic adolescent patients with Turner syndrome using multidetector computed tomography (MDCT) instead of echocardiography. Twenty subjects diagnosed with Turner syndrome who had no cardiac symptoms were included. Blood pressure and electrocardiography (ECG) was checked. Cardiovascular abnormalities were checked by MDCT. According to the ECG results, 11 had a prolonged QTc interval, 5 had a posterior fascicular block, 3 had a ventricular conduction disorder. MDCT revealed vascular abnormalities in 13 patients (65%). Three patients had an aberrant right subclavian artery, 2 had dilatation of left subclavian artery, and others had an aortic root dilatation, aortic diverticulum, and abnormal left vertebral artery. As for venous abnormalities, 3 patients had partial anomalous pulmonary venous return and 2 had a persistent left superior vena cava. This study found cardiovascular abnormalities in 65% of asymptomatic Turner syndrome patients using MDCT. Even though, there are no cardiac symptoms in Turner syndrome patients, a complete evaluation of the heart with echocardiography or MDCT at transition period to adults must be performed.     

A clinical study of 57 children with fetal anticonvulsant syndromes

BACKGROUND—Anticonvulsants taken in pregnancy are associated with an increased risk of malformations and developmental delay in the children. To evaluate the pattern of abnormalities associated with prenatal anticonvulsant exposure further, we undertook a clinical study of 57 children with fetal anticonvulsant syndromes.
METHODS—Fifty two children were ascertained through the Fetal Anticonvulsant Syndrome Association and five were referred to the Aberdeen Medical Genetics Service. Pregnancy and medical history were obtained through a standardised questionnaire and interview and the children were examined.
RESULTS—Thirty four (60%) were exposed in utero to valproate alone, four (7%) to carbamazepine alone, four (7%) to phenytoin alone, and 15 (26%) to more than one anticonvulsant. Forty six (81%) reported behavioural problems, 22 (39%) with hyperactivity or poor concentration of whom four (7%) had a diagnosis of attention deficit and hyperactivity disorder. Thirty four (60%) reported two or more autistic features, of whom four had a diagnosis of autism and two of Asperger's syndrome. Forty four (77%) had learning difficulties, 46 (81%) had speech delay, 34 (60%) had gross motor delay, and 24 (42%) had fine motor delay. Nineteen (33%) had glue ear and 40 (70%) had joint laxity involving all sizes of joints. Of 46 who had formal ophthalmic evaluation, 16 (34%) had myopia.
CONCLUSIONS—Speech delay, joint laxity, glue ear, and myopia are common in the fetal anticonvulsant syndromes and autistic features and hyperactivity form part of the behavioural phenotype.


Keywords: fetal anticonvulsant syndrome; fetal valproate syndrome; teratogen; birth defects     

先天性左冠状动脉主干闭锁3例超声心动图特征及文献复习

目的 通过研究先天性左冠状动脉主干闭锁（LMCAA）的超声心动图表现,提高对LMCAA诊断的准确性.方法 回顾性分析经冠状动脉造影证实的3例LMCAA患儿的超声心动图检查结果,并复习相关文献,总结LMCAA超声心动图特征.结果 LMCAA特异性超声心动图特征：①主动脉左冠状动脉窦内无左冠状动脉主干开口,左冠状动脉主干近心端闭锁呈盲端,远心端内径细窄,发育不良;②右冠状动脉内径增宽;③多切面未显示左冠状动脉与肺动脉确切连接的证据.LMCAA非特异性超声心动图特征：①左心室明显扩大,左室收缩功能可正常或减低;②二尖瓣腱索、乳头肌回声显著增强,可伴有二尖瓣脱垂.彩色多普勒超声特征：①收缩期二尖瓣口可见中至大量反流信号;②左、右冠状动脉之间形成细小侧支循环; ③左冠状动脉前降支和回旋支血流为逆向灌注（向心性）;④发育不良的左冠状动脉虽然在肺动脉周围分布,但彩色多普勒超声不能显示其与肺动脉连接的确切逆灌血流信号.结论 LMCAA有特异性的超声心动图特征,提高对LMCAA的全面认识是诊断本病的关键.     

Pulmonary stenosis in recipient twins in twin-to-twin transfusion syndrome: report on 3 cases and review of literature

This report describes 3 cases of pulmonary stenosis in the recipient twin in twin-twin transfusion syndrome. Fetal echocardiography showed cardiomegaly, tricuspid valve regurgitation, and increased reverse flow in the inferior vena cava, as signs of congestive heart failure in all 3 cases. We diagnosed 2 cases of pulmonary stenosis by fetal echocardiography prenatally and confirmed our findings in all 3 cases postnatally. Two cases underwent postnatal balloon valvuloplasty to release the pulmonary valvular stenosis in neonatal period. The third one died soon after delivery and autopsy showed a slightly thickened pulmonary valve. One of the cases was diagnosed in the early second trimester (20 weeks of pregnancy), the earliest detection of fetal pulmonary stenosis reported in literature. The presence of high peak velocity of the pulmonary artery at 20 weeks of pregnancy preceded the development of pulmonary stenosis in this case. This supports the hypothesis that alterations in fetal hemodynamics may result in structural cardiac abnormality.     

Multiple spontaneous coronary artery dissections in association with anomalous origin of right coronary and intramural coronary artery dysplasia.

We present a case of sudden death due to spontaneous acute coronary artery dissection. In addition, there was a healing spontaneous coronary dissection, intramural coronary artery dysplasia, and an anomalous origin of the right coronary artery from the pulmonary trunk. The coincidence of multiple spontaneous coronary dissections, coronary arterial dysplasia, and anomalous origin of the right coronary artery is unique.     

Morphometric study of the human fetal heart. I. Arterial segment

This study measured the dimensions of the great arteries of normal human fetal hearts at an early fetal stage (between 13-20 weeks post-fertilization) in 103 fetuses obtained by necropsy. Different segments of the aorta and the pulmonary artery were dissected and their external diameters measured under stereoscopic magnification. All segments showed linear growth during this period of fetal development. Ranges in median values of external diameters associated with the pulmonary artery were: 2.1-4.2 mm for the valve ring; 2.2-4.2 mm for the main pulmonary trunk; 1.2-2.5 mm for the right pulmonary artery; 0.9-2.18 mm for the left pulmonary artery; and 4.0-8.0 mm for the length of the main pulmonary trunk. Similarly, in the aorta, median diameters were: 2.1-4.2 mm for the ascending aorta; 1.92-3.8 mm for the aortic arch; 1.45-3.0 mm for the aortic isthmus; and 1.75 -3.35 mm for the descending aorta. The diameter of the ductus arteriosus ranged between 1.2-2.45 mm. The growth rates of the pulmonary artery and the aorta were similar. The diameter of the ascending aorta was found to be greater than that of the descending aorta and the right pulmonary artery was wider than the left pulmonary artery. In addition, the magnitude of growth in the various aortic segments was different and the ratios obtained between the aortic isthmus and the ascending and descending aortae, ranged between 0.66-0.93. This study provides important morphometric reference information concerning the dimensions and growth of the great arteries of the fetal heart and has clinical application in pediatric cardiac surgery and echocardiography.     

Demonstration of an anomalous connection between the left coronary artery and the pulmonary artery using a multislice CT 64

In this article, we describe two cases of anomalous connection of the left coronary artery. The first case is an infant of 4 years with an anomalous origin of the left anterior descending (LAD) artery and the diagonal branches and a circumflex artery which originated from the pulmonary artery. The second case is an adult of 50 years with the coronary artery originating from the pulmonary artery. Anomalous origin of the left coronary artery from the pulmonary artery is an uncommon congenital cardiac anomaly with an incidence of 0.25% among all congenital heart defects (Parale and Pawar [2006], J Assoc Physicians India 54:397-399). The originality of this communication consists in the use of a multislice CT scanner as a support for the angiography. The result is an original image with three dimensional details; in the case of the infant, it was determinant in the choice of the surgical approach.     

Unexpected sudden death of a 19-year-old female with congenital single coronary artery ostium during exertion

Coronary artery anomalies are associated often with myocardial ischemia or sudden cardiac death. A 19-year-old woman who participated in an exertive game lost consciousness upon one such exertion. She was taken to a hospital where she died on the same day. An autopsy revealed that she had bifurcated coronary arteries, which arose from one coronary ostium in the left sinus of Valsalva. The right coronary artery arose from the left sinus and traveled between the aorta and the pulmonary trunk. The heart as well as the cardiac conduction system depended exclusively on the single coronary artery ostium for oxygenated blood supply, and the unbalanced blood distribution on her exertion probably led to sudden cardiac death. The case highlights the medicolegal importance of unexpected sudden cardiac death related to an anomalous origin of the coronary arteries.     

Major Primary Congenital Coronary Artery Anomalies: An Angiographic Study

Congenital Coronary artery anomalies are found in about 1 % population (0.6% to 1.5% in different geographic studies). Angiographic recognition of these anomalies is important because of their clinical significance (sudden death) and importance in patients undergoing coronary interventions or cardiac surgery. Our study included 3215 patients who underwent diagnostic coronary angiography during the 2 years period from 2008 to 2010. Twenty nine (0.90%) patients (22 male and 7 female) had major congenital coronary anomalies of which twenty seven (93.10%) patients had anomalies of origin and distribution while two (6.89%) had coronary artery fistulae. Right coronary artery was the commonest anomalous vessel, involved in 14 (48.27%) patients. It was originating from the left sinus of Valsalva in 10, from the non-facing aortic sinus in 2 and from left anterior descending artery in 2 patients. Anomalous origin of left circumflex artery was the second commonest anomaly, seen in 10 (34.48%) patients. Anomalous left anterior descending artery was found to be originating from right coronary artery in 2 (6.89%) and anomalous left coronary artery from right coronary artery was seen in one (3.4%) patient. Among patients with coronary fistulae, one (3.4%) had fistulae between the left anterior descending artery and the main pulmonary artery, one (3.4%) between the conal artery and the right atrium. The fistulae in our series were small & without significant shunt circulation. Atherosclerotic plaques in anomalous arteries were seen in only 8 (27.58%) patients, significantly less than the incidence (51.5%) of overall coronary artery disease in 3215 patients studied in this series. In two (6.89%) patients only the anomalous vessels were involved in coronary artery disease. Congenital coronary artery anornalies do not appear to be associated with an increased risk for development of coronary atherosclerosis. Recognition of coronary anomalies is important in patients undergoing coronary angiography, coronary interventions and cardiac surgery. Variations in the frequency of major congenital coronary anomalies may have a genetic background.     

一侧肺动脉起源于升主动脉的外科处理

目的探讨一侧肺动脉起源于升主动脉的外科处理方法.方法自1993年3月～2001年8月共收治5例一侧肺动脉起源于升主动脉患者,其中4例为右肺动脉起源于升主动脉,合并动脉导管未闭4例、卵圆孔未闭2例及室间隔缺损1例;另1例为左肺动脉起源于升主动脉合并法乐氏四联症.均在全麻低温低流量下行根治术.结果1例因呼吸衰竭、弥散性血管内凝血(DIC)术后24天死亡,4例治愈.结论一侧肺动脉起源于升主动脉手术效果良好.     

Pulmonary artery catheter insertion in a patient of dextrocardia with anomalous venous connections

In a young adult patient having situs solitus with dextrocardia the attempted pulmonary artery catheter placement for emergency mitral valve replacement required an unduly long length (50cm) of catheter insertion to get into right ventricle and then into pulmonary artery. Although catheter coiling was suspected initially, chest x-ray taken after successfully placement revealed an uncommon congenital anomalous venous connection i.e. right internal jugular opening into left sided superior vena cava then into inferior vena cava after running all along the left border of the heart. With the result, it required to pass 50cm of PA catheter to get into right ventricle in our patient. This emphasizes the need to look for abnormal venous connections during echocardiography and x-ray screening in congenital heart disease. Fluoroscopy is recommended when an unusual length of pulmonary artery catheter insertion is required to enter the pulmonary artery.     

Right coronary ostium agenesis with absence of the right coronary artery: a rare case of non-ST elevation coronary syndrome

We present a case with right coronary ostium agenesis with anomalous origin of the right coronary artery from the left circumflex artery, which caused a non-ST elevation coronary syndrome. A review of the literature indicates this to be an extremely rare case.     

Unusual origin and course of the left pulmonary artery.

An infant with a cardiac murmur was found to have a patent arterial duct and an anomalous left pulmonary artery. The duct was surgically ligated at the age of 8 months, and she remained free of cardiac or respiratory symptoms up to her death at 6 years from an unrelated intestinal condition. An anomaly was discovered at post mortem examination; the left pulmonary artery arose from the right pulmonary artery and passed behind the trachea to enter the left lung. We describe and illustrate the anatomic features of this well-recognized entity, discuss the embryological substrate, and refer to the clinical implications.     

Association between left ventricular diastolic dysfunction and severity of chronic obstructive pulmonary disease

OBJECTIVES:

The prevalence of electrocardiographic and echocardiographic abnormalities in chronic obstructive pulmonary disease according to disease severity has not yet been established. The aim of this study was to assess the prevalence of electrocardiographic and echocardiographic abnormalities in chronic obstructive pulmonary disease patients according to disease severity.

METHODS:

The study included 25 mild/moderate chronic obstructive pulmonary disease patients and 25 severe/very severe chronic obstructive pulmonary disease patients. All participants underwent clinical evaluation, spirometry and electrocardiography/echocardiography.

RESULTS:

Electrocardiography and echocardiography showed Q-wave alterations and segmental contractility in five (10%) patients. The most frequent echocardiographic finding was mild left diastolic dysfunction (88%), independent of chronic obstructive pulmonary disease stage. The proportion of right ventricular overload (p<0.05) and blockage of the anterosuperior division of the left bundle branch were higher in patients with greater obstruction. In an echocardiographic analysis, mild/moderate chronic obstructive pulmonary disease patients showed more abnormalities in segmental contractility (p<0.05), whereas severe/very severe chronic obstructive pulmonary disease patients showed a higher prevalence of right ventricular overload (p<0.05), increased right cardiac chamber (p<0.05) and higher values of E-wave deceleration time (p<0.05). Age, sex, systemic arterial hypertension, C-reactive protein and disease were included as independent variables in a multiple linear regression; only disease severity was predictive of the E-wave deceleration time [r² = 0.26, p = 0.01].

CONCLUSION:

Chronic obstructive pulmonary disease patients have a high prevalence of left ventricular diastolic dysfunction, which is associated with disease severity. Because of this association, it is important to exclude decompensated heart failure during chronic obstructive pulmonary disease exacerbation.     

Total anomalous origin of the coronary circulation from the right pulmonary artery

Origin of both coronary arteries from a branch of the pulmonary artery is rare and has not been reported as a cause of sudden unexpected death. We report autopsy findings of a 14-day male infant in previously good health who died suddenly. From the proximal right pulmonary artery arose a single coronary artery, which branched into the right and left main coronary arteries. The right proximal coronary artery coursed between the aorta and pulmonary trunk, and the left main traveled along the anterior proximal aorta. The distal course of the coronary circulation was normal. There was concentric subendocardial healing myocardial infarction. No other congenital anomalies were identified. Total anomalous origin of the coronary arteries from the pulmonary trunk or artery should be considered in cases of sudden unexpected death in infants.     

小儿左冠状动脉异常的矫治术麻醉管理方法探讨

目的分析小儿起源于肺动脉的左冠状动脉异常矫治手术的麻醉特点,为今后开展类似手术提供可行的麻醉管理方法。方法回顾性分析2006年3月至2010年7月本院20例小儿起源于肺动脉的左冠状动脉异常矫治术的麻醉管理方法。结果采用静吸复合全麻,术中均未出现急性心衰或心梗,CPB时间为58～204（80.6±44.4）min,主动脉阻断时间为25～125（53.4±32.2）min,开放主动脉后均自动复跳,适时应用血管活性药物,以保证麻醉平稳,停CPB时SBP为（78.6±8.0）mmHg,DBP为（45.4±3.5）mmHg,HR为（130.8±10.5）次/min,术中无死亡及麻醉并发症。1例术后第2天死于严重低心排综合征,死亡率为5%,其余痊愈出院。结论小儿左冠状动脉异常矫治术以静吸复合全麻的方法 ,辅以严密监测,尽力维持血流动力学稳定,积极采取各种措施避免加重心肌缺血的麻醉管理方法是正确可行的,可以推广应用于术前有心功能损害的手术。     

Congenital heart disease associated with sporadic Kallmann syndrome

A 17-year-old boy with Kallmann syndrome had complex congenital heart disease that included double-outlet right ventricle, d-malposition of the great arteries, right aortic arch, and hypoplastic main pulmonary artery. He had neurosensory hearing loss and mental retardation. The 7 previously reported patients with Kallmann syndrome and cardiac abnormalities were short with height ≥2 standard deviations below the mean for age (5/7), lacked a family history of Kallmann syndrome (6/6), and were mentally retarded (4/4). Patients presenting with Kallmann syndrome and congenital heart defects appear to represent a distinct subgroup of patients with Kallmann syndrome. The cause of this association is unclear, but may involve either autosomal recessive inheritance, sporadic dominant mutation, or a shared teratogenic event during the first trimester of gestation. © 1993 Wiley-Liss, Inc.     

胎儿动脉导管缺如的尸体解剖分析

目的对胎儿先天性动脉导管缺如进行尸体解剖分析,以提高该疾病诊断的精准性。方法回顾2011年1月至2019年9月北京安贞医院经超声心动图畸形筛查发现胎儿先天性心脏畸形引产而进行尸体解剖病例400例,检查胎儿心血管畸形及内脏的畸形情况,对其动脉导管缺如进行分析总结。结果400例胎儿先天性心脏病中,动脉导管缺如24例,检出率6%,男女各12例,左位主动脉弓19例,右位主动脉弓5例,21例具有肺动脉主干,3例无肺动脉主干及分支。具体情况如下:(1)肺动脉狭窄伴动脉导管缺如15例,伴发主要心血管畸形:单心室6例,房间隔缺损6例,单心房4例,右心房异构4例,右心室双出口4例,静肺脉异位引流4例,法洛四联症3例,永存左上腔静脉3例;(2)肺动脉闭锁伴动脉导管缺如7例,3例无肺动脉主干,4例肺动脉闭锁伴有狭窄的肺动脉主干,均可见体-肺动脉侧支;(3)法洛四联症伴肺动脉瓣缺如综合征及动脉导管缺如1例,肺动脉扩张;(4)主-肺动脉间隔缺损伴动脉导管缺如1例,肺动脉正常。动脉导管缺如伴发主要心外畸形:脾缺如7例,肺异常7例,内脏反位7例。结论胎儿动脉导管缺如常合并复杂先天性心血管畸形;动脉导管缺如合并肺动脉闭锁常伴体-肺动脉侧支;内脏畸形与伴随的先天性心血管畸形有关。     

A case of anomalous bronchial artery ramified from coronary artery

There have been no anatomical reports on the origin of the bronchial artery derived from the coronary artery. In a 2006 cadaveric dissection course, an anomalous bronchial artery that reached the middle lobe of the right lung from the left coronary artery was observed in an 88-year-old Japanese man. In this specimen, the circumflex branch of the left coronary artery passed under the left auricle in the coronary sulcus and bifurcated to three branches (left marginal branch, posterior left ventricular branch, atrial branch), which were 3.2–3.4 mm in diameter. The atrial branch intersected on the surface of the great cardiac vein, ran along the oblique vein of the left atrium, and reached the atrial side of the transverse pericardial sinus, and then divided into two branches. One of them led to the right atrium. The other branch passed between two right superior pulmonary veins, which derived from superior and middle lobes of the right lung, respectively, through the hilum of the lung along the right superior pulmonary vein derived from the middle lobe, and finally became the bronchial artery in the middle lobe of the right lung. In the middle lobe, the bronchial artery divided into a thin branch along the pulmonary vein for the lateral segment, ran along the surface of the right middle bronchus, and then reached the medial segment, being wedged between the segmental bronchus and vein.