Polysplenia and situs inversus in siblings. Case reports

Heterotaxy syndromes, otherwise laterality defects, are variations from anatomic left-right asymmetry. Situs inversus is the complete reversal of the normal situs, still situs ambiguus is the randomisation of the normal organ position. Situs ambiguus may be manifested as asplenia or polysplenia syndrome. Normal situs and both types of the heterotaxy syndromes may appear among some affected families, whereas the different situs are rarely expressed in the same family. We describe an autosomal-recessive inherited familial heterotaxy syndrome with two affected siblings - one of whom has situs inversus, and the other with polysplenia syndrome. The polysplenia syndrome was diagnosed by fetal echocardiography. Since the chromosomal or molecular diagnosis of laterality defects are accessible only in X-linked heterotaxy syndromes, the fetal echocardiography is the earliest available diagnostic method in this field. Therefore, fetal echocardiography has great importance for affected families.     

Ivemark syndrome with agenesis of the corpus callosum: a case report with a review of the literature

Asplenia associated with situs ambiguus, symmetric liver, bilateral trilobulated lungs, and a complex heart defect was diagnosed on autopsy in a 14-day-old infant. Furthermore, examination of the brain displayed agenesis of the corpus callosum (ACC) with pachygyria and hydrocephalus. The characteristic association of asplenia with visceroatrial heterotaxia is traditionally named after the Swedish pediatrician, Ivemark. Although exceptional, association of Ivemark syndrome with callosal agenesis has been reported recently. The concept of 'developmental fields' describes morphogenetically reactive units of the embryo determining and controlling the development of complex structures in a hierarchical manner. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development, as well as decussation defects such as ACC, are considered as defects of the primary developmental field. Therefore, additional callosal agenesis in Ivemark syndrome may be a coherent and synchronic defect in the primary developmental field rather than a causally independent malformation.     

Fetale Heterotaxie-Syndrome

The spectrum of conditions associated with heterotaxy syndromes includes a wide variety of cardiovascular and visceral anomalies that are differently distributed amongst the two clinical variants, left and right isomerism, and which determine the intrauterine as well as the postnatal course and outcome. An exact prenatal diagnosis is therefore warranted. Important sonographic markers in heterotaxy syndromes are the associated anomalies of the situs and cardiac defects. Prenatal differentiation of the two clinical variants can be based on the anomalies, the course of the inferior vena cava and the presence of a heart block.In left isomerism, mortality is highest in the prenatal period due to frequent association with a complete heart block and subsequent intrauterine heart failure. In the postnatal period, the outcome depends mainly on the associated cardiac malformations and their ability to be corrected.In contrast, in right isomerism the mortality is highest in the postnatal period. This is mainly due to the more complex type of associated cardiac malformations.     

Disorders of laterality and heterotaxy in the foetus

Disorders of laterality and heterotaxy syndromes are rare diseases with an incidence of 1-1.5/10,000 live births. They are associated with numerous viscerocardiac anomalies and malformations. In particular, heterotaxy syndromes are associated with complex cardiac and extracardiac malformations that have an important impact on the prenatal and postnatal course. A prenatal differentiation between the 2 main variants of heterotaxy--left and right isomerism--is possible by assessment of cardiac rhythm, anomalies of caval veins and descending aorta and concomittant cardiac and extracardiac anomalies. An exact diagnosis is mandatory for adequate counselling of the parents and planning of postnatal care. Left isomerism has a high intrauterine mortality, caused by early atrioventricular block with subsequent cardiac failure and hydrops. In contrast, right isomerism has a high postnatal mortality due to the more complex type of cardiac defects and splenic disorders. The type of associated cardiac and extracardiac anomalies determines the postnatal morbidity and mortality. Polysplenia and asplenia may be associated with immunological disorders, that cannot be ruled out in the prenatal period, and further complicate the postnatal course.     

Contribution of 3D-ultrasound in the heterotaxy syndromes: about four cases and review of the literature

The position or location of the organs and vessels is usually classified into three types: situs solitus, situs inversus, and situs ambigus. Situs solitus is the usual arrangement of organs and vessels within the body. Only 0.6 to 0.8% of patients with situs solitus and levocardia have associated congenital heart diseases. Situs inversus refers to an anatomic arrangement that is the mirror image of situs solitus. The incidence of congenital heart disease is increased to 3 to 5% in the patients with situs inversus. The patients with heterotaxy have congenital heart disease in high incidence, ranging from 50 to nearly 100%. We present four cases diagnosed in our department in a period of 18 months. With these four cases and a review in the literature, we explore the definitions and characteristics of heterotaxy syndromes and we study the role of 3D ultrasound.     

Right Fetal Cardiac Axis: Clinical Significance and Associated Findings

Objective: To ascertain the clinical significance of right fetal cardiac axis.Methods: Fetal cardiac axis was assessed prospectively in ultrasound examinations of 16,562 fetuses over a 6-year period.Results: Twenty-two fetuses had a right cardiac axis. When classified by ventricular and atrial configuration, six fetuses had mirror-image hearts with situs inversus, 12 had rotation of the heart axis alone, and four had inversion of the ventricles. Fourteen of the 22 had underlying structural cardiac defects, most of which were atrioventricular septal defects, double outlet right ventricles, or common atria. The chromosomes and/or phenotypes of all 22 were normal. All four fetuses with polysplenia and asplenia died. Major extracardiac defects were few (two) but lethal.Conclusion: Right cardiac axis in the fetus is associated with a high incidence of structural cardiac defects. In the absence of severe extracardiac defects, polysplenia, or asplenia, neonatal outcome was good.     

Two Cases of Mayer-Rokitansky-Kuster-Hauser Syndrome with Situs Inversus Totalis: Coincidence or Co-Existence?

Congenital absence of uterus and vagina, the Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS), results from defective müllerian duct development during female embryogenesis; it is the second most common cause of primary amenorrhea. Atypical forms of MRKHS (type B) represent a heterogeneous group of disorders with associated anomalies of other organ systems which frequently includes the renal and skeletal systems and several individually occurring malformations.We report two cases with MRKHS in which we diagnosed situs inversus totalis incidentally during radiologic examinations. Abdominal situs inversus describes the mirror-image arrangement of the intra-abdominal organs in the abdominal cavity and it is characterized by the presence of multiple congenital anomalies.In this report we attempt to question whether the association between MRKHS and situs inversus is a rare feature of the müllerian dysgenetic spectrum or whether it is the result of random association.     

A case report of polysplenia syndrome associated with genital tract duplication anomaly

Polysplenia syndrome is a condition that persists as a defect of lateralisation, the embryonic process by which the site of body organs is determined. The most frequent manifestations of this syndrome, in addition to polysplenia are complex cardiac malformations, situs inversus, and bilobed lungs. Laterality defects have been known to be due to autosomal recessive inheritance. We report a unique case of polysplenia syndrome in association with genital tract duplication anomaly.     

Evaluation of prenatal diagnosis of associated congenital heart diseases by fetal ultrasonographic examination in Europe

Ultrasound scans in the mid trimester of pregnancy are now a routine part of antenatal care in most European countries. With the assistance of Registries of Congenital Anomalies a study was undertaken in Europe. The objective of the study was to evaluate prenatal detection of congenital heart defects (CHD) by routine ultrasonographic examination of the fetus. All congenital malformations suspected prenatally and all congenital malformations, including chromosome anomalies, confirmed at birth were identified from the Congenital Malformation Registers, including 20 registers from the following European countries: Austria, Croatia, Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands, UK and Ukrainia. These registries follow the same methodology. The study period was 1996-1998, 709 030 births were covered, and 8126 cases with congenital malformations were registered. If more than one cardiac malformation was present the case was coded as complex cardiac malformation. CHD were subdivided into 'isolated' when only a cardiac malformation was present and 'associated' when at least one other major extra cardiac malformation was present. The associated CHD were subdivided into chromosomal, syndromic non-chromosomal and multiple. The study comprised 761 associated CHD including 282 cases with multiple malformations, 375 cases with chromosomal anomalies and 104 cases with non-chromosomal syndromes. The proportion of prenatal diagnosis of associated CHD varied in relation to the ultrasound screening policies from 17.9% in countries without routine screening (The Netherlands and Denmark) to 46.0% in countries with only one routine fetal scan and 55.6% in countries with two or three routine fetal scans. The prenatal detection rate of chromosomal anomalies was 40.3% (151/375 cases). This rate for recognized syndromes and multiply malformed with CHD was 51.9% (54/104 cases) and 48.6% (137/282 cases), respectively; 150/229 Down syndrome (65.8%) were livebirths. Concerning the syndromic cases, the detection rate of deletion 22q11, situs anomalies and VATER association was 44.4%, 64.7% and 46.6%, respectively. In conclusion, the present study shows large regional variations in the prenatal detection rate of CHD with the highest rates in European regions with three screening scans. Prenatal diagnosis of CHD is significantly higher if associated malformations are present. Cardiac defects affecting the size of the ventricles have the highest detection rate. Mean gestational age at discovery was 20-24 weeks for the majority of associated cardiac defects.     

Congenital diaphragmatic hernia. Two cases with early prenatal diagnosis and increased nuchal translucency

The early ultrasound prenatal diagnosis of congenital diaphragmatic hernia is uncommon and suggests a poor outcome. We report 2 cases diagnosed at 10 and 12 weeks' gestation, with increased fetal nuchal translucency thickness (4 and 11 mm) and associated abnormalities (complex heart defect in one and many malformations in the other, including duodenal atresia and asplenia). In 1 case, the baby was delivered vaginally at 36 weeks, but neonatal death occurred; the pregnancy was terminated at 15 weeks in the second case.     

Changing trends in pregnancy outcome among HIV-infected women between 1985 and 1997 in two southern French university hospitals

OBJECTIVE: To determine the utility of the first-trimester fetal nuchal translucency (NT) thickness in the prediction of fetal cardiac malformations. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynecology and Medical Genetics, University of Szeged. METHODS: The pre- and postnatal course and outcome, and the relationship between the first-trimester fetal NT thickness and fetal congenital heart defects (CHDs) in 4309 pregnancies ended up with birth or therapeutic abortion between January 1998 and June 2000 were registered. Prenatal care included first- and second-trimester fetal sonography at weeks 10-13 and 18-20, respectively. RESULTS: 4251 births and 58 first- and second-trimester therapeutic abortions due to lethal congenital malformations or chromosomal abnormalities were recorded. Altogether 209 (4.9%) congenital malformations were detected, 39 (18.7%) of which were heart defects with normal karyotype. At birth, 151 congenital malformations were diagnosed, 34 of them were known prenatally. The prevalence of CHDs was 9 per 1000 pregnancies. The measurement of fetal NT thickness was available in 35 of the 39 fetuses with heart defects: it was > or = 3 mm in 18 (51.4%) and <3 mm in 17 (48.6%). A sensitivity of 51.4% was found at a cutoff of 3mm. CONCLUSIONS: An increased NT thickness in chromosomally normal fetuses was found to be highly associated with CHDs and identified in more than half of the affected cases. Furthermore, an increased NT of > or = 3 mm can be regarded a selection criterion for early second-trimester targeted fetal echocardiography and for increased fetal and neonatal surveillance.     

Síndrome de bridas amnióticas: caso clínico y revisión del tema

Amniotic band syndrome is a set of congenital birth defects consisting of constriction rings and limb or digit amputations, associated with the presence of amniotic bands. The incidence of this complication is low and its occurrence is sporadic. This syndrome usually causes constriction rings in the distal end of limbs or digits, which, in severe cases, can lead to complete amputation of the limbs or other malformations. Only 29-50% of cases are diagnosed prenatally. We report the case of a patient with an ultrasonographic diagnosis of amniotic band syndrome in week 12 of pregnancy.     

Uterovaginal Prolapse in a Newborn with Meningomyelocele: Case Report

BackgroundNeural tube defects are a group of congenital malformations in which the spinal column is bifid as a result of failed closure of the embryonic neural tube. Although not common, they might be complicated with pelvic organ prolapse mostly due to abnormal innervation and the resulting atrophy of the pelvic floor musculature.CaseIn this case report we present a newborn with uterovaginal prolapse in the setting of meningomyelocele, in whom the prolapse of pelvic organs spontaneously ameliorated after surgical correction of meningomyelocele.     

Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs

A study was conducted to determine the frequency of malformations among newborn infants of mothers receiving anticonvulsive therapy, with and without supplementation of folic acid. In the retrospective part of the study, the frequency of congenital malformations among the 66 newborn of 24 women who received anticonvulsive drugs without the supplementation of folic acid was 15% (10 children). The defects noted were congenital heart disease, cleft lip and palate, neural tube defects and skeletal abnormalities. Three out of the 10 children were stillborn or died immediately after delivery. In the prospective study of the 22 epileptic women with folic acid supplementation to their anticonvulsive regimen, 33 infants were born alive, without congenital malformations and of normal body weight. The teratogenic activity of anticonvulsant drugs seems to be mediated by interference with folic acid metabolism, and such activity might be influenced by hereditary and environmental factors. When an epileptic woman wishes to become pregnant, it is recommended that folic acid be added to her regimen.     

Prenatal diagnosis of a large de novo terminal deletion of chromosome 11q

OBJECTIVE: To describe the prenatal phenotype of the 11q deletion syndrome (Jacobsen syndrome) and present the molecular characterization of the deletion in the case presented. CASE: Ultrasound at 18 and 20 weeks of gestation, on a 34-year-old woman who presented for amniocentesis, revealed slow movements, oligohydramnios and dilatation of the cerebral ventricles in the fetus. Maternal and paternal ages were 34 and 38 years, respectively. RESULTS: Prenatal karyotyping of cultured amniotic fluid cells revealed an 11q terminal deletion, 46,XX,del(11)(q23) (Jacobsen syndrome). Real-time quantitative PCR analysis was used to identify and map the breakpoint physically to a 45-kb region located 14.5 Mb from the 11q telomere. Polymorphic DNA marker analysis showed that DNA sequences on the paternally derived chromosome are deleted. At autopsy, facial dysmorphism without major malformations was recorded. Examination of the internal organs disclosed the following abnormalities: a Meckels' diverticulum of 4-mm length, adhesion between the gall bladder and the transverse colon, and bilaterally bilobed lungs without further situs anomalies. CONCLUSION: Our case demonstrates significant phenotypic variability of Jacobsen syndrome at midtrimester pregnancy; the syndrome may be manifested at this stage only by mild to moderate ventriculomegaly of the brain.     

人巨细胞病毒感染与先天性畸形关系的探讨

探讨人巨细胞病毒宫内感染与先天性畸形的关系,并确定巨细胞病毒感染组织细胞细胞。方法利用聚合酶链反应技术,对近８年来我院尸检畸形儿４１例同期尸检非畸形儿１９例进行了主要脏器的ＨＣＭＶ检测,对部分ＰＣＲ阳性的组织本,用原位杂交技术确定ＨＣＭＶ易感组织细胞类型。     

Fetal complete heart block: antenatal diagnosis, significance and management

Complete heart block was diagnosed prenatally in 21 fetuses. Associated structural cardiac defects were present in 18 fetuses, in particular complete atrioventricular canal with atrial isomerism (5 cases), and 'corrected' transposition of the great arteries (4 cases). Maternal systemic lupus erythematosus was proved in only one case. In 11 fetuses, intra-uterine congestive heart failure with the signs of non-immune hydrops fetalis occurred. In all 11 fetuses, the hydrops was associated with a cardiac defect, in particular complete atrioventricular canal with atrial isomerism in 5 cases. A review of the literature confirms that only the association of complete heart block and cardiac malformation can cause intra-uterine congestive heart failure, whereas in the case of fetal complete heart block without cardiac malformation or with prenatally hemodynamically insignificant cardiac malformation, congestive heart failure is rare. Only 30% of newborns with complete heart block have associated cardiac malformations. In our series, however, 86% of the fetuses with complete heart block had cardiac malformations. The most important reason for this percentage discrepancy is that almost all fetuses with associated severe cardiac defects, in particular atrioventricular canal defects, develop heart failure which frequently results in prenatal death. Thus, fetal deaths are not included in pediatric statistics. Nevertheless, fetuses with isolated complete heart block generally do not develop heart failure and in almost all of the cases are born alive.     

Hemocromatosis neonatal: resultado satisfactorio de la terapia con inmunoglobulina por vía intravenosa a partir de la semana 14 de gestación

Neonatal hemochromatosis is a rare congenital disease that causes severe liver failure, leading to a high mortality rate (80-90%). The cause remains unknown but the alloimmune hypothesis is gaining ground. Intravenous immunoglobulin therapy has been proven to be effective in ameliorating the consequences of this entity.     

ACOG practice bulletin. Neural tube defects. Number 44, July 2003. (Replaces committee opinion number 252, March 2001).

Neural tube defects (NTDs) are congenital structural abnormalities of the brain and vertebral column that occur either as an isolated malformation, along with other malformations, or as part of a genetic syndrome. Isolated (ie, nonsyndromic) NTDs occur in 1.4-2 per 1,000 pregnancies and are the second most common major congenital anomaly worldwide (cardiac malformations are first). In the United States, approximately 4,000 fetuses are affected each year of which one third are either aborted or spontaneously lost. Anencephaly accounts for one half of all cases of NTDs and is incompatible with life; with treatment, 80-90% of infants with spina bifida survive with varying degrees of disability. Most importantly, NTDs are among the few birth defects for which primary prevention is possible; prenatal screening and diagnosis are widely available, and prenatal therapy is being investigated.