Conotruncal Abnormalities Research Articles

Conotruncal abnormalities

Conotruncal abnormalities

A Rare Fındıng of Chromosome 22q11.2 Deletıon Syndrome: Multıcystıc Dysplastık Kıdney

The 22q11.2 deletion syndrome also known as velocardiofacial/DiGeorge syndrome is the most common microdeletion syndrome seen in every 4000 live births. The 22q11.2 deletion syndrome is an autosomal dominant inherited disease and approximately 90% of the patients have spontaneous heterozygous deletions on chromosome 22q11.2. The classic triad of the syndrome is conotruncal heart abnormalities, immune deficiency due to hypoplastic thymus and hypocalcemia due to parathyroid hypoplasia. The clinical features may vary depending on the age of the patient. The diagnosis is made by demonstrating microdeletion using FISH method in cases suspected with clinical and laboratory findings. In this article a case of 22q11.2 deletion syndrome is presented in an adolescent girl with multicystic dysplastic kidney which rarely accompanies this syndrome.

Sonography of the Outflow Tracts of the Fetal Heart Part 1 – Normal Anatomy and Common Anatomical Variants

The four-chamber view of the fetal heart is still widely used as the only sonographic view for detection of congenital heart disease (CHD). However, inherent limitations of the four-chamber view in detecting abnormalities of the major vessels necessitate expanding the routine scan to include the outflow tracts. Conotruncal abnormalities in particular are often not detected on the four-chamber view. Assessment of the heart and outflow tracts is accomplished by sequential transverse planes starting in the upper abdomen and ending in the superior mediastinum. Grey-scale 2-D images, complemented by colour and pulsed Doppler which help quantify direction and velocity flow within the insonated vessel are now considered the standard. Although there is initially a steep, slow learning curve, successful evaluation of the outflow tracts can be accomplished within 5 minutes by an experienced examiner. Grey-scale images complemented by colour, directional power Doppler and pulsed Doppler will allow identification of most major CHD cases. This paper describes the normal anatomy in each of these transverse planes, as well as common variants and pitfalls that constitute the normal two-dimensional scan, that must be mastered prior to evaluating the numerous abnormalities that may be encountered. Most infants with CHD are born to mothers without specifically defined risk factors, and it is for this reason, that the emphasis on fetal heart evaluation has evolved to routine screening of both low- and high-risk pregnancies. The four-chamber view of the fetal heart is still widely used as the only sonographic view for detection of congenital heart disease (CHD). However, because of the inherent limitations in the four-chamber view in detecting anomalies of the outflow tracts, the sensitivity for detection of CHD varies from 48 to 63% in some series.1-3 When evaluation of the outflow tracts is performed as well, the detection rate of CHD increases to over 90%.4

EP03.07: Prenatal diagnosis of 22q11.2 microdeletion: minor cardiac finding detected in mid‐trimester scan associated with severe bilateral perisylvian polymicrogyria in late gestation

A microdeletion in chromosomal region 22q11.2 results in DiGeorge syndrome (OMIM 188400) and velocardiofacial syndrome (OMIM 192430). The most frequent findings in 22q11.2 microdeletion are facial dysmorphism, velopharyngeal insufficiency, conotruncal cardiac abnormalities (usually associated with thymic hypoplasia), and speech delay. Polymicrogyria (PMG) is a rare feature of the microdeletion presenting with developmental delay, microcephaly, and epilepsy. We report the case of a male fetus, whose 23 weeks anatomical scan depicted two right pulmonary arterial vessels (instead of one) observed in longitudinal plane through the aortic arch. In view of the otherwise normal fetal echocardiography, this finding was interpreted as proximal bifurcation of right pulmonary artery. At 30 weeks sonographic scan, malformation of cortical development was suspected. The scan revealed bilateral dysmorphic and shallow Sylvian fissures with irregular cortical surface, surrounded by enlarged subarachnoid spaces. MRI performed at 32 weeks depicted frontal loss of brain volume with irregular dysmorphic cortex, mainly in the perisylvian regions, consistent with severe polymicrogyria. In view of poor prognosis, the parent asked to terminate the pregnancy. Fetal autopsy revealed perisylvian polymicrogyria, hypoplastic thymus, and unilateral anorchia. Microdeletion in 22q11.2 region was detected on fetal CMA. Revision of the 2nd trimester scan demonstrated normal brain anatomy, however the thymus was small for gestational week. Conclusions: Minor finding in great vessels associated with hypoplastic thymus can be associated with severe PMG in late gestation as a result of 22q11.2 microdeletion.

Circulating mRNA in Maternal Plasma at the Second Trimester of Pregnancy: A Possible Screening Tool for Cardiac Conotruncal and Left Ventricular Outflow Tract Abnormalities.

Maternal plasma is a source of circulating placental nucleic acids. This study was designed to detect aberrantly expressed placental mRNA genes circulating in the maternal plasma of pregnancies affected with fetal conotruncal anomalies (CNTRA) and left-ventricular outflow tract (LVOT) obstruction in the second trimester of pregnancy. This was a retrospective monocentric study conducted from 1 Jan 2016 to 31 Dec 2016. NanoString technology was used to identify aberrantly expressed genes, comparing 36 women carrying a fetus with CNTRA or LVOT obstruction to 42 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real-time polymerase chain reaction. Linear discriminant analysis was used to combine all the mRNA species with discriminant ability for CNTRA and LVOT obstruction. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated for the two affected groups versus controls. Three genes with differential expression, namely MAPK1, IQGAP1 and Visfatin were found. The ROC curves yielded detection rates of 60 and 62.5% at a false-positive rate of 5% for CNTRA and LVOT, respectively. These data suggested that molecular screening of CNTRA and LVOT obstruction in the second trimester is feasible. Prospective studies are needed to test the discriminant ability of these genes and to calculate the predictive positive value in the general population.

Out Flow Tract Abnormalities

Cong. Heart disease is the leading cause for neo-natal morbidity & mortality. Pre-natal detection improves neo-natal out come. Out flow tract evaluation complimenting the four chamber view improves the detection of cardiac abnormalities particularly the Cono-truncal abnormalities. Sweep & Rotational techniques are practiced to evaluate the out-flow tracts. The left and right ventricular out flow tract evaluation helps in detecting abnormal septo-aortic continuity, Abnormal cross overs and Abnormal semi-lunar valves.

DORV–Double Outlet Right Ventricle

Double outlet right ventricle is a cono-truncal abnormality in which the great arteries arise either predominantly or entirely from the right ventricle. DORV is categorized based on the spatial relationship of great arteries, location of VSD and presence or absence of outflo Care Ultrasonography (POw obstruction. Great arteries relationship and location of VSD are of four types. 4 chamber view is usually normal, 5 chamber view reveals VSD and origin of great arteries. 3VT shows discrepancy of great arteries. D/D – TOF and CTGA.

Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries.

ABSTRACTOriginating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development.

Short-Term Costs and Hospitalization Rates in Patients With Adult Congenital Heart Disease After Pulmonic Valve Replacement

In the adult congenital heart disease (ACHD) population, pulmonary valve replacement (PVR) is a common intervention, its benefit, however, has been incompletely investigated. This study investigates short- and intermediate-term outcomes after PVR in ACHD. Using State Inpatient Databases from the Healthcare Cost and Utilization Project, we investigated both hospitalization rate and financial burden accrued over the 12-month period after PVR compared with the 12 months before. Among 202 patients who underwent PVR, per patient-year hospitalization rates doubled in the year after PVR compared with the year before (0.16 vs 0.36, p= 0.006). With the exception of postprocedural complications, the most common reasons for hospitalization were unchanged after surgery: 22% of patients were admitted with equal or greater frequency after PVR. These patients experienced higher inpatient costs both at index admission and in the year after PVR (p= 0.004 and p <0.001, respectively). Univariate predictors of increased hospitalizations after PVR were age ≥50 years (p= 0.016), transposition of the great arteries, or conotruncal abnormalities (p <0.001), lipid disorders (p= 0.025), hypertension (p= 0.033), and number of chronic conditions ≥4 (p= 0.004). Multivariate analysis identified transposition of the great arteries or conotruncal abnormalities as an independent risk factor for increased hospitalization and cost post-PVR (p ≤0.001). In conclusion, short-term costs and hospitalization rates increase after PVR in a small group of patients with ACHD.

Lesion-Specific Factors Contributing to Inhospital Costs in Adults With Congenital Heart Disease

The population of adults with congenital heart disease (ACHD) in the United States is growing rapidly with concomitant increases in care costs. We sought to define the variables having the greatest influence on annual cost of inpatient care in patients with ACHD in the United States. To do so, we conducted a retrospective analysis of admissions in patients >18 years old with a 3-digit International Classification of Disease, Ninth Revision, code of 745 to 747 from the State Inpatient Databases of Arkansas (2008 to 2010), California (2003 to 2012), Florida (2005 to 2012), Hawaii (2006 to 2010), Nebraska (2003 to 2011), and New York (2005 to 2012). We selected variables we believed would have the greatest effect on care costs and built a series of multivariable regression models grouping patients by congenital lesion to examine the relative contribution of the specified variables to total annual inpatient cost. We analyzed a total of 68,314 patients aged 57 ± 18.6 years, 51% of whom were women. The multivariable regression model had an overall R(2) of 0.35. Readmission was responsible for 10.3% of annual inpatient cost among all patients with ACHD and had the greatest effect on inpatient care cost for each congenital lesion except Eisenmenger syndrome and conotruncal abnormalities, for both of which it was the second most significant contributor. Other major contributors to annual inpatient care costs included length of stay and operative procedures. In conclusion, rehospitalization is the most significant contributor to annual inpatient cost for individual patients with ACHD in the United States, regardless of underlying anatomy.

Ventricular Septal Defect with Overriding Great Artery, Differential Diagnosis, Case Presentation, and Review of Literature

Abstract Embryologically, conotruncal abnormalities result from abnormal development of the conotruncal septum expressing variably as double outlet right ventricle, tetralogy of Fallot, absent pulmonary valve syndrome, complete transposition, corrected transposition, and pulmonary atresia with ventricular septal defect (PA-VSD). It is not very uncommon to see a VSD with one single large artery overriding the defect, along with nonvisualization of the right ventricular outflow tract and ventricular origin of the Pulmonary artery. In situations with above findings and a near normal four chamber heart view the differential diagnosis include common arterial trunk (CAT), and pulmonary atresia with VSD and rare disorders like aortic atresia. CAT is characterized by a single great artery supplying the coronary, cranial and pulmonary circulation. Similar findings in PA-VSD may create confusion in prenatal diagnosis of these two conditions, more so in CAT type II/III. The diagnosis of CAT type I is comparatively easy as the pulmonary artery arises immediately beyond the origin of the trunk. This article discusses a case, the approach to and differential diagnosis of a single great artery overriding a VSD with a near normal four chamber view. The role of cardiac screening during the early morphology scan and the role of 4D imaging with color and power Doppler angiography are also highlighted for the correct diagnosis and description of spatial relationships of the vessels and chambers. Correct prenatal diagnosis of these conditions is important for patient counseling and prognostication.

Characterising adequacy or inadequacy of the borderline left ventricle: what tools can we use?

Borderline left ventricle refers to a spectrum of left ventricular underdevelopment, typically associated with other cardiac anomalies. The left ventricle may be mildly hypoplastic, as is sometimes seen accompanying aortic coarctation, or it can be severely hypoplastic, as is seen in hypoplastic left heart syndrome. For patients with a borderline left ventricle that is at either extreme, the treatment decision is relatively straightforward. Those with the most severe form of left ventricle hypoplasia will require single ventricle palliation or cardiac transplantation, whereas those with the mildest form may not need any intervention. It is the management strategy of children that fall within the grey zone of the spectrum, which continues to be controversial and remains variable within and among different institutions. Cardiac diseases with associated left ventricle hypoplasia include critical aortic stenosis, mitral stenosis, coarctation of the aorta, arch hypoplasia, cor triatriatum, unbalanced common atrioventricular canal, Shone's complex, total anomalous pulmonary venous return, and complex conotruncal abnormalities. In this review, we will discuss the assessment and management of infants with borderline left ventricle with critical aortic stenosis or arch obstruction and associated mitral anomalies.

Prevalencia de hallazgos anormales en ecocardiogramas fetales en el Hospital Universitario de Santander, Bucaramanga (Colombia), 2007-2013

&lt;p class="Pa35"&gt;&lt;strong&gt;Objetivo: &lt;/strong&gt;describir la prevalencia de hallazgos anormales en ecocardiogramas fetales y los hallaz­gos anormales más frecuentemente encontrados.&lt;/p&gt;&lt;p class="Pa35"&gt;&lt;strong&gt;Materiales y métodos&lt;/strong&gt;: estudio de corte trans­versal, en pacientes con indicación para realizar ecocardiograma fetal por presencia de factores de riesgo o sospecha de anomalía en el ultrasonido obs­tétrico, atendidas en la Unidad Materno-Fetal del Hospital Universitario de Santander, Bucaramanga (Colombia), institución de salud de tercer nivel de complejidad, que atiende población perteneciente al aseguramiento subsidiado por el Estado, en el periodo comprendido entre 2007-2013. Se realizó muestreo consecutivo. El examen lo realizó un in­vestigador con un ecógrafo marca MEDISON V10, por medio de la ecocardiografía 2D con Doppler color y Doppler espectral. Se describen la edad gestacional (EG), la fracción de eyección (FE) y las anomalías encontradas, que se clasificaron en cinco subgrupos: anomalías de la unión AV derecha, de la unión AV izquierda, cono truncales, del &lt;em&gt;septum &lt;/em&gt;y trastornos de la conducción. Los resultados se presentan mediante estadística descriptiva.&lt;/p&gt;&lt;p class="Pa35"&gt;&lt;strong&gt;Resultados&lt;/strong&gt;: en el periodo descrito se realizaron 99 ecocardiogramas fetales, 40 de ellos fueron descri­tos como normales (40,4 %) y 56 fueron categoriza­dos como anormales (59,6 %). Se encontró un total de 130 hallazgos anormales: 33 anomalías septales, (25,3 %), 32 anomalías conotruncales (24,6 %), 27 anomalías de la unión AV derecha (20,7 %), 12 de la unión AV izquierda (9,2 %) y 7 desórdenes de conducción (5,3 %).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusiones: &lt;/strong&gt;la prevalencia de hallazgos anor­males en la ecocardiografía fetal en gestantes con indicación de realizar ecocardiograma fue de 59,6 % en nuestra institución.&lt;/p&gt;

142 Genomics in Adult Patients with Congenital Heart Disease (CHD): The Norpap Database

Background Adults with CHD now outnumber the paediatric population due to greater than 90% survival to the age of 18. About 400 syndromic types account for 25% of the CHD population; some of these are associated with high inheritance rates about which the adult CHD need counselling. The NORPAP database is derived from a dedicated adult CHD service started in 1993. Methods We reviewed the NORPAP database (n = 2322) of which 264 patients (144M, 120F) with syndromic appearance had been genotyped. Mean age 35 years (16–89). 224 genotype positive and 40 genotype negative were identified. Spectrums of syndromes are described below in the Figure 1. The highest incidence of CHD with genotype was AV canal defects, but also VSD, conotruncal abnormalities and aortopathies (Marfan, L-D, E. D. IV). Phenotypes and cardiac defects were studied as most patients had more than one associated lesions. Table 2 describes the association. Importantly 144 (55%) patients had cardiac surgery of which 32 (27%) required a second intervention required surgical intervention (higher incidence in Trisomy 21). Incidence of arrhythmias was low n = 19 (7%); 11 (4%) had device therapy. 47 (18%) patients had PAH-CHD of whom 11 were on targeted therapy. Endocarditis occurred in 4 patients only, surprising given the number with 22q11deletion. The incidence of IHD to date is low (3). Conclusion Clinical syndromes with CHD are seen frequently seen in adult CHD clinics. Only 10% of the NORPAP database has been genotyped despite increasingly close involvement with clinical geneticists. Due limited availability of genetic testing in previous eras, many adult CHD survivors should have phenotype-genotype assessment not only to enhance parenthood counselling and cascade screening, but, increasingly, risk stratification of recognised comorbidities.

Bronchial arteries: anatomy, function, hypertrophy, and anomalies.

The two main sources of blood supply to the lungs and their supporting structures are the pulmonary and bronchial arteries. The bronchial arteries account for 1% of the cardiac output but can be recruited to provide additional systemic circulation to the lungs in various acquired and congenital thoracic disorders. An understanding of bronchial artery anatomy and function is important in the identification of bronchial artery dilatation and anomalies and the formulation of an appropriate differential diagnosis. Visualization of dilated bronchial arteries at imaging should alert the radiologist to obstructive disorders that affect the pulmonary circulation and prompt the exclusion of diseases that produce or are associated with pulmonary artery obstruction, including chronic infectious and/or inflammatory processes, chronic thromboembolic disease, and congenital anomalies of the thorax (eg, proximal interruption of the pulmonary artery). Conotruncal abnormalities, such as pulmonary atresia with ventricular septal defect, are associated with systemic pulmonary supply provided by aortic branches known as major aortopulmonary collaterals, which originate in the region of the bronchial arteries. Bronchial artery malformation is a rare left-to-right or left-to-left shunt characterized by an anomalous connection between a bronchial artery and a pulmonary artery or a pulmonary vein, respectively. Bronchial artery interventions can be used successfully in the treatment of hemoptysis, with a low risk of adverse events. Multidetector computed tomography helps provide a vascular road map for the interventional radiologist before bronchial artery embolization.

Atrioventricular septal defects: Natural history, echocardiographic, electrocardiographic, and radiographic findings in 26 cats

ObjectivesTo evaluate signalment, echocardiographic, electrocardiographic, and radiographic findings as well as natural history in a group of cats with atrioventricular septal defects (AVSD). Animals26 client owned cats. MethodsMedical records were reviewed retrospectively for signalment, morphologic type of AVSD, presence of concurrent congenital heart disease (ConcCHD), diagnostic findings, and natural history. ResultsSeventeen cats had an isolated AVSD; 13/17 had a partial and 4/17 had a complete AVSD. Double outlet right atrium (DORA) was diagnosed in 4/17 cats. Of those with a partial AVSD, 7/13 had an atrial communication while 6/13 had a ventricular communication. Congestive heart failure (CHF) developed in 5/17 cats; all 3 cats diagnosed with a DORA not lost to follow-up developed pulmonary edema. Sudden death was documented in 4/17 (23.5%). The 5 year survival was 53.0% (9/17). Concurrent congenital heart disease was identified in 9/26 cats with 7/9 having a conotruncal abnormality. Electrocardiography was performed in 14 cats with 11/14 diagnosed with a conduction disturbance. ConclusionsOverall the echocardiographic and electrocardiographic findings with AVSD are similar to that seen in humans. Cats may have a higher prevalence than humans of partial AVSD with ventricular communication only as well as a higher prevalence of DORA. Cats with an AVSD have an overall guarded prognosis although some can live for a protracted time.

OP13.01: Cerebral blood flow redistribution in fetuses with congenital heart disease

Congenital heart disease (CHD) is known to be associated to and increased risk of abnormal neurodevelopmental outcome, even in the absence of surgical intervention. Recent studies have established a strong link between fetal arterial redistribution and poorer neurodevelopmental outcome after birth. The aim of this study was to explore cerebral blood flow perfusion in fetuses with CHD during the third trimester of pregnancy. Retrospective case series of fetuses with a diagnosis of major CHD. Fetuses affected by placental insufficiency were excluded. Middle cerebral artery (MCA) and cerebro-placental ratio (CPR), expressed as the ratio between MCA and umbilical artery (UA) PI, were analysed in patients with CHD from 28 weeks of gestation. The proportion of fetuses with abnormal MCA PI or CPR, defined as below the 5th centile for a given gestational age, was calculated and the distribution of abnormal Doppler finding among different types of CHD was analysed using Chi-square test for trend. 132 normally grown fetuses with CHD were included in the analysis. The proportion of fetuses with abnormal Doppler findings, expressed MCA or CPR <5th centile, was 62.41% (95% confidence intervals, C.I. 53.9%-70.2%). Signs of brain redistribution were present in 46.15% (95% C.I. 23.2%-70.1%) of fetuses with AVSD, 61.54% (95% C.I. 45.7%-75.1%) in cases with VSD, in 66.67% (95% C.I. 46.2-82.2) of the cases of cono-truncal abnormalities, 72.41% (95% C.I. 54.1-85.5) of cases with obstruction of the right or left outflow tracts and in 30.00% (95% C.I. 10.3-70.8) in fetuses with transposition of the great arteries with a significant statistical difference among the different categories of CHD (p = 0.0002). Normally grown fetuses with CHD have a higher than expected rate of redistribution of cerebral blood flow in the absence of placental insufficiency. This finding suggests a possible pathophysiological mechanism for the high rate of neurodevelopmental outcome observed in these patients.

Maternal serum placental growth factor at 11–13 weeks' gestation and fetal cardiac defects

To investigate the relationship between fetal heart defects and maternal serum placental growth factor (PlGF), a marker of placental angiogenesis. Maternal serum PlGF, pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11-13 weeks' gestation were compared in 68 cases of isolated fetal major heart defects and 340 normal controls. Variables were converted into multiples of the median (MoM) after adjustment for gestational age, maternal age, racial origin, weight, parity and method of conception, and then compared between groups. The cardiac defects included 11 cases of obstruction of the left ventricular outflow tract (LVOT), 25 conotruncal abnormalities and 32 valve defects. The median PlGF-MoM in the heart defect group was lower than in controls (0.80 (interquartile range (IQR), 0.57-1.08) vs 1.00 (IQR, 0.79-1.32); P < 0.0001). Low PlGF levels were observed in the presence of conotruncal and valve defects but not in the presence of LVOT defects. There was no significant difference between the group with fetal heart defects and controls in PAPP-A-MoM (0.95 (IQR, 0.68-1.28) vs 1.01 (IQR, 0.70-1.39); P = 0.292) or UtA-PI-MoM (1.01 (IQR, 0.84-1.28) vs 0.99 (IQR, 0.80-1.20); P = 0.396). In pregnancies with isolated fetal heart defects there is evidence of impaired placental angiogenesis in the absence of impaired placental perfusion and function.

Reliability of fetal thymus measurement in prediction of 22q11.2 deletion: a retrospective study using four‐dimensional spatiotemporal image correlation volumes

To evaluate the thymic-thoracic ratio (TT-ratio) method in assessment of the fetal thymus in normal fetuses and in those with cardiac abnormalities, in the presence or absence of 22q11.2 deletion. Database records were reviewed for cases of conotruncal and arch abnormalities found on fetal echocardiography between January 2007 and September 2011. The 22q11.2 deletion status was retrieved and cases in which this was not known were excluded from the analysis, as were fetuses with aneuploidy or other genetic disorders. An additional 55 normal fetuses were analyzed as a control group. The TT-ratio was measured retrospectively using stored spatiotemporal image correlation (STIC) volume datasets. Sixty-nine fetuses with relevant cardiac diagnoses were identified and, of these, 18 (26%) had 22q11.2 deletion. The mean gestational age at diagnosis was 22 weeks. Significant pairwise differences, but also overlap, were observed between all three groups (i.e. fetuses with heart defects with and without the 22q11.2 deletion and controls). The mean TT-ratio was 0.44 in our normal control group and was significantly smaller in fetuses with 22q11.2 deletion, corresponding to previously published data. However, the mean TT-ratio in the group with conotruncal anomalies but without the 22q11.2 deletion was also smaller than that in controls, in contrast to previously published data. The TT-ratio was above the normal mean, regardless of fetal karyotype, in all cases of interrupted aortic arch. The TT-ratio method is a feasible and potentially useful tool during detailed fetal heart assessment. However, the absolute measurement is not reliable for prediction of 22q11.2 deletion and the obtained results should therefore be interpreted with caution. Fetal karyotyping should be recommended in cases with conotruncal heart abnormalities, irrespective of the TT-ratio.

Transposition of great arteries: new insights into the pathogenesis.

Transposition of great arteries (TGA) is one of the most common and severe congenital heart diseases (CHD). It is also one of the most mysterious CHD because it has no precedent in phylogenetic and ontogenetic development, it does not represent an alternative physiological model of blood circulation and its etiology and morphogenesis are still largely unknown. However, recent epidemiologic, experimental, and genetic data suggest new insights into the pathogenesis. TGA is very rarely associated with the most frequent genetic syndromes, such as Turner, Noonan, Williams or Marfan syndromes, and in Down syndrome, it is virtually absent. The only genetic syndrome with a strong relation with TGA is Heterotaxy. In lateralization defects TGA is frequently associated with asplenia syndrome. Moreover, TGA is rather frequent in cases of isolated dextrocardia with situs solitus, showing link with defect of visceral situs. Nowadays, the most reliable method to induce TGA consists in treating pregnant mice with retinoic acid or with retinoic acid inhibitors. Following such treatment not only cases of TGA with d-ventricular loop have been registered, but also some cases of congenitally corrected transposition of great arteries (CCTGA). In another experiment, the embryos of mice treated with retinoic acid in day 6.5 presented Heterotaxy, suggesting a relationship among these morphologically different CHD. In humans, some families, beside TGA cases, present first-degree relatives with CCTGA. This data suggest that monogenic inheritance with a variable phenotypic expression could explain the familial aggregation of TGA and CCTGA. In some of these families we previously found multiple mutations in laterality genes including Nodal and ZIC3, confirming a pathogenetic relation between TGA and Heterotaxy. These overall data suggest to include TGA in the pathogenetic group of laterality defects instead of conotruncal abnormalities due to ectomesenchymal tissue migration.