A human laterality disorder associated with a homozygous WDR16 deletion.

The laterality in the embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid, which is maintained by the rotary movement of monocilia on the nodal cells. Defects manifest by abnormal formation and arrangement of visceral organs. The genetic etiology of defects not associated with primary ciliary dyskinesia is largely unknown. In this study, we investigated the cause of situs anomalies, including heterotaxy syndrome and situs inversus totalis, in a consanguineous family. Whole-exome analysis revealed a homozygous deleterious deletion in the WDR16 gene, which segregated with the phenotype. WDR16 protein was previously proposed to play a role in cilia-related signal transduction processes; the rat Wdr16 protein was shown to be confined to cilia-possessing tissues and severe hydrocephalus was observed in the wdr16 gene knockdown zebrafish. The phenotype associated with the homozygous deletion in our patients suggests a role for WDR16 in human laterality patterning. Exome analysis is a valuable tool for molecular investigation even in cases of large deletions.

Mouse model of heterotaxy with single ventricle spectrum of cardiac anomalies.

Heterotaxy arises from a failure of the embryo to establish normal left-right asymmetry and is known to affect 3% of infants with congenital heart disease. A recessive mutation causing heterotaxy was recovered in a mouse mutagenesis screen focused on congenital heart defects. Homozygote mutants exhibit abnormal situs in the thoracic and abdominal cavities. Dextrocardia, levocardia, or mesocardia was seen together with right pulmonary isomerism and complex structural heart defects in the single ventricle spectrum. A dominant chamber of left ventricular morphology positioned on the left or right is seen together with transposition of the great arteries. Right atrial isomerism with or without total anomalous pulmonary venous connection was observed in half of the mutants. Because ciliary motion at the embryonic node is required for the specification of laterality, we examined the tracheal epithelia of newborn mice as a proxy for the nodal cilia. However, videomicroscopy showed no defect in ciliary motion. Genome scanning using polymorphic microsatellite markers mapped the mutation to a 3.3 Mb interval on mouse chromosome 7. None of the genes previously described for familial heterotaxy were found in this interval, indicating a novel mutation in this mouse model of heterotaxy.

Arrangement of the systemic and pulmonary venous components of the atrial chambers in hearts with isomeric atrial appendages.

BACKGROUND: The morphological definition of atrial chambers, and the determination of atrial laterality, are based on analysis of the structure of the atrial appendages. The systemic and pulmonary venous connections to the heart, nonetheless, are important in the management of patients having isomeric appendages. In this study, therefore, we analysed the morphology of the postero-superior walls of the atrial chambers so as to provide evidence concerning the morphogenetic background of those hearts, and to improve operative management. METHODS: We reviewed 15 autopsied specimens with isomeric right appendages, and 10 with isomeric left appendages, paying particular attention to the morphology of the systemic and pulmonary venous connections. The postero-superior walls of the atrial chambers can be made up of the atrial body, the systemic venous components, or the pulmonary venous component. We analysed the contributions made by each of these components. RESULTS: The postero-superior walls of the atrial chambers were markedly variable, but could be grouped into five patterns. Bilaterally well-developed systemic venous components and absence of the pulmonary venous component within the hypoplastic atrial body were present in 9 hearts with extracardiac pulmonary venous connections in the setting of right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the hypoplastic atrial body, were present in 5 hearts with intracardiac pulmonary venous connections in right isomerism. Bilaterally well-developed systemic venous components, and a hypoplastic pulmonary venous component within the sizable atrial body, were present in 1 heart with an intracardiac pulmonary venous connection in right isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of one systemic venous component, were present in 7 hearts with left isomerism. A well-developed pulmonary venous component within the atrial body, and hypoplasia of bilateral systemic venous components, were present in 3 hearts with left isomerism. CONCLUSIONS: The postero-superior walls of the atrial chambers in hearts with isomeric atrial appendages can be analysed on the basis of a compound structure made of bilateral systemic venous components, a central pulmonary venous component, and the body of the atrium. Hearts with isomeric right appendages have absence or hypoplasia of the pulmonary venous component, while hearts with isomeric left appendages have hypoplastic systemic venous components.

[Double inlet left ventricle. Morphopathology and surgical anatomy]. / Doble entrada ventricular izquierda. Morfopatología y anatomía quirúrgica.

Because of the possibility of surgical treatment of double inlet left ventricle, its basic morphologic features of surgical and imaging importance are analyzed. Seventeen hearts were studied with the segmental sequential system. The situs was solitus in thirteen; dextroisomerism in three and levoisomerism in one. The atrioventricular valves were separated in nine; there was a common atrioventricular valve in eight; straddling of the atrioventricular valve in seven and stenosis in two. The rudimentary right ventricle was to the right side in twelve hearts and to the left side in five. The discordant ventriculoarterial connection was the most frequent (seven), followed by the concordant one (five) and double outlet right ventricle (five). There was pulmonary stenosis in five. The ventricular septum did not reach the crux cordis. The ventricular septal defect was bigger in straddling atrioventricular valves than in valves completely open into the left ventricle, being restrictive in ventriculoarterial concordance. Surgical treatment varies as the complexity of this cardiopathy does, from cardiac septation to palliation procedures. The morphologic knowledge of this cardiac malformation is basic to interpret correctly the diagnostic imaging.

A case of malrotation and situs ambiguus.

Isolated levocardia is a rare condition in which intestinal malrotation may be encountered. The case herein reported is particularly uncommon and raises a number of questions about the development of abdominal symmetry.

Division of the main pulmonary artery: suboptimal palliation for the patient with a univentricular heart.

We describe a patient in whom a thrombus formed in the distal main pulmonary artery stump after a bidirectional Glenn procedure with division of the main pulmonary artery and in whom a restrictive inlet ventricular septal defect also developed. These findings emphasize the importance of maintaining antegrade flow through the pulmonary trunk and providing dual sources of ventricular outflow with a Damus-Kaye-Stansel anastomosis in patients with a univentricular heart without pulmonary stenosis.

[Double outlet right ventricle with discordant atrioventricular connection. Clinical study]. / Doble cámara de salida del ventrículo derecho con conexión atrioventricular discordante. Estudio clínico.

The clinical and anatomic findings were reviewed in 17 patients with double-outlet right ventricle and atrioventricular discordance. Ten cases had atrial situs solitus, seven with right-sided heart three with left-sided heart. Seven cases had atrial situs inversus, five with left-sided heart and two with right-sided heart. All cases presented ventricular septal defect, 13 subvalvar pulmonary stenosis, two tricuspid regurgitation and two complete atrioventricular block. The spatial relationship between the arterial valves are variable. Most cases in atrial situs solitus had a left-sided and anterior aorta and all patients in atrial situs inversus had a right-sided and anterior aorta. In this study we compared the anomalies found in our cases with double outlet right ventricle with those in 58 patients with corrected transposition. Absolute, relative and attributable risks were calculated for the presence of subvalvular pulmonary stenosis, ventricular septal defect, tricuspid regurgitation and atrioventricular block for each the two groups. We concluded that patients with double-outlet right ventricle are more prone to present ventricular septal defect and subvalvar pulmonary stenosis, while those with corrected transposition have a greater likelihood of presenting with tricuspid regurgitation and atrioventricular block. There is no typical clinical picture for the malformations. Symptoms depend upon the associated anomalies. The final diagnosis is best achieved by the echocardiographic and angiocardiographic studies, but electrocardiogram and chest radiograph may suggest the presence of a discordant atrioventricular connection.

An ultrasonic approach to the diagnosis of cardiac situs, connections, and malpositions.

Two-dimensional echocardiography of cardiac situs, connections, and malpositions from a variety of planes is discussed.

[Pulmonary atresia with interventricular communication. Review of concepts]. / Atresia pulmonar con comunicación interventricular. Revisión de conceptos.

The purpose of this paper is to clarify the definition and anatomic characteristics of pulmonary atresia with ventricular septal defect. This complex congenital cardiac malformation produces great controversy in the literature. We analyze some embryological aspects, the right ventricular outflow tract anatomy and pulmonary arterial pattern with the various patterns of collateral blood supply. A good understanding of these anatomic characteristics is of great importance in the hemodynamic and angiographic diagnostic procedures and in the planning of surgical correction. The differential diagnosis with other congenital heart diseases with single outlet from the heart is discussed.

The three types of criss-cross heart: a simple rotational anomaly.

Criss-cross heart is an angiographically confusing malformation where apparent crossing but not mixing of contrast medium is seen at atrioventricular level. The malformation can be understood by a clockwise or counter-clockwise ventricular rotation. In the normal heart or one with complete transposition ventricular rotation is clockwise. With corrected transposition rotation occurs in a counter-clockwise fashion. One case of criss-cross heart with associated corrected transposition and two criss-cross hearts occurring with complete transposition are reported.

Analysis of atrioventricular junction, ventricular mass, and ventriculoarterial junction in 43 specimens with atrial isomerism.

We have analysed the atrioventricular junction, ventricular mass, and ventriculoarterial junction in 43 hearts with isomeric atrial chambers. Of the hearts, 32 had atrial chambers of bilateral right morphology while 11 had atrial chambers with bilateral left atrial characteristics. Among the hearts with right atrial isomerism, there were 13 biventricular hearts, all with ambiguous atrioventricular connection. Eight had a common valve and five had two atrioventricular valves. In the other 19 hearts, the atrial chambers were connected to only one ventricular chamber, 18 having double inlet ventricle through a common valve and the other having absence of the left atrioventricular connection. In these univentricular hearts, all possible types of ventricular morphology were found. The ventriculoarterial junction among these hearts with right isomerism showed great variation. In the hearts with left atrial isomerism, nine hearts had two ventricles and two were univentricular. The biventricular hearts all had ambiguous atrioventricular connection, six via a common valve and three via two valves. The two univentricular hearts both had double inlet via a common valve, one to a chamber of right ventricular type and the other to a chamber of left ventricular type. Both had rudimentary chambers of complementary pattern. The ventriculoarterial junction again showed much variation. Statistical analysis showed that pulmonary obstruction and a univentricular heart were both significantly more frequent in association with right compared with left isomerism. Significant differences were also noted in the two groups in terms of ventriculoarterial connections and infundibular morphology.

The relationship between single ventricle and small outlet chamber and straddling and displaced tricuspid orifice and valve.

This paper deals with the anatomic differences between single ventricle and small outlet chamber, straddling tricuspid orifice and valve, and displaced tricuspid orifice and valve. In single ventricle, both atrioventricular orifices enter a chamber which contains the sinuses of both definitive ventricles, while a small outlet chamber represents the definitive infundibulum of the right ventricle. In straddling tricuspid orifice and valve, the primitive left ventricle contains the sinus of the definitive infundibulum of the right ventricle. In straddling tricuspid orifice and valve, the primitive left ventricle contains the sinus of the definitive left ventricle and also a portion of the sinus of the definitive right ventricle. The primitive right ventricle contains the infundibulum and part of the sinus of the definitive right ventricle. In displaced tricuspid orifice, the primitive left ventricle contains the sinus of the definitive left and almost all of the sinus of the definitive right ventricle. However, a posterior ventricular septum is formed, so that a portion of sinus or apical recess of the definitive right ventricle is included in the primitive right ventricle together with its infundibulum. Possible embryologic speculations are offered to account for these entities. The differences in the anatomy of these entities may be important to the surgeon.

Absent tricuspid valve with aortic atresia in mixed levocardia (atria situs solitus, L-loop). A hitherto undescribed entity.

Clinical, angiographic and pathologic features are described in a 36-hour-old male infant with mixed (discordant) levocardia, aortic valve atresia, absent tricuspid (left atrioventricular) valve and resultant massive cardiomegaly. This is the first reported case of this type of complex in a heart with discordant chambers. A possible embryologic explanation is offered for the concomitant presence of semilunar valve atresia and absence of the tricuspid valve.

An elderly case of mixed levocardia with situs inversus including inverted atria and complete transposition of the great vessels--an autopsied case.

We reported on the autopsy of a 35-year-old man who had mixed levocardia with situs inversus including atrial inversion, transposition of the great vessels, and other complex cardiac malformations. Levocardia was discussed.

The surgical anatomy of pulmonary atresia with ventricular septal defect: pseudotruncus.

This is a study of 172 heart specimens with pulmonary atresia and ventricular septal defect (VSD)--pseudotruncus. These are divided into simple and complicated types. In the simple type the following may be of importance from the surgical standpoint: (1) the size of the pulmonary arteries, (2) the origin of the aorta, (3) the amount of pulmonary flow, (4) the size of the left side of the heart, (5) the presence of bronchial and/or abnormal systemic supply to the lungs, (6) the coronary circulation, and (7) the presence of intra- and extracardiac associated abnormalities. The following factors may be important in the complicated types: (1) Complete transposition may accompany the complex; (2) instead of the VSD there may be a common atrioventricular (AV) orifice; (3) the pulmonary atresia with VSD may be associated with tricuspid or mitral atresia or with common or single ventricle; (4) the entity may be associated with abnormal position of the entire heart or some of its component chambers.