Can we predict 22q11 status of fetuses with tetralogy of Fallot?

OBJECTIVE: To determine if chromosome 22q11 deletion status can be predicted in fetuses with tetralogy of Fallot as regards additional phenotypic anomalies. METHODS: One hundred and fifty-one consecutive fetuses with tetralogy of Fallot without or with pulmonary atresia were screened for 22q11 deletion. Additional echographic features [increased nuchal translucency (NT), intrauterine growth retardation (IUGR), polyhydramnios, extracardiac malformations, pulmonary arteries abnormalities] were noted. RESULTS: Twenty-five fetuses had a 22q11 deletion (16.6%). Increased NT, polyhydramnios and IUGR were more frequent in fetuses with 22q11 deletion as well as pulmonary arterial abnormalities. When these different features were present in the same fetus with tetralogy of Fallot, 22q11 deletion can be predicted with a sensitivity of 88%. CONCLUSION: Simple echographic features can help to predict 22q11 status in fetuses with tetralogy of Fallot. This may improve the efficiency of prenatal screening for this defect.     

DiGeorge syndrome: new insights

Most patients with the clinical features of DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes share a common genetic cause, namely, a deletion of chromosome 22q11, and define the most common deletion syndrome known at this time. The clinical features of the 22q11 deletion syndrome are highly variable between individuals; some have subtle findings, whereas others are severely affected. The most common clinical features include specific types of congenital heart disease, hypocalcemia, immunodeficiency, facial dysmorphia, palate anomalies, velopharyngeal dysfunction, renal anomalies, and speech and feeding disorders as well as neurocognitive, behavioral, and psychiatric disorders. A significant number of patients with tetralogy of Fallot, truncus arteriosus, an interrupted aortic arch, isolated aortic arch anomalies, and perimembranous ventricular septal defects have a 22q11 deletion. Routine testing for a 22q11 deletion in this subset of patients should be considered to provide anticipatory medical intervention and appropriate family counseling.     

Fetal echocardiography. VIII. Aortic root dilatation--a marker for tetralogy of Fallot

Tetralogy of Fallot has increased in incidence during the past decade. Although abnormalities of the four-chamber screening examination of the fetal heart identifies structural anomalies associated with semilunar and atrioventricular valve hypoplasias, the anomalies associated with tetralogy of Fallot are not as readily identifiable from the four-chamber view alone. This study was designed to determine whether aortic root dilatation, commonly observed in the newborn with tetralogy of Fallot, is a marker for tetralogy of Fallot diagnosed in utero. In 45 normal (control) fetuses the biparietal diameter, head circumference, abdominal circumference, and femur length were measured and M-mode measurements were made of the biventricular outer dimension and aortic root dimension. The aortic root dimension from seven fetuses (18, 19, 20, 23, 32, 33, and 34 weeks' gestation) with tetralogy of Fallot was increased in dimension when compared with cardiac (biventricular outer dimension) and noncardiac biparietal diameter, head and abdomen circumferences, and femur length parameters. In conclusion, incorporation of aortic root imaging with the four-chamber view of the fetal heart during a routine screening examination allows for identification of fetuses with tetralogy of Fallot.     

Prenatal diagnosis of smith-magenis syndrome (del 17p11.2)

Smith-Magenis syndrome is associated with a microdeletion of the short arm of chromosome 17 with phenotypic abnormalities including dysmorphic facies, self-injurious behavior, mental and neurologic disturbances, and congenital cardiac defects. The majority of patients present in mid-childhood or adulthood. We describe a fetus in which the diagnosis of Smith-Magenis syndrome was made at 16 weeks of gestation following amniocentesis for increased risk for Down syndrome detected by second-trimester maternal serum screening. Ultrasound evaluation revealed multiple fetal anomalies. The pregnancy was terminated at 20 weeks of gestation. Post-mortem findings included dysmorphic facial features, tetralogy of Fallot, a thymic duct remnant, pancreatic islet cell hyperplasia, and abnormal lung fissuring. This represents the second case of prenatally diagnosed Smith-Magenis syndrome. Molecular genetic techniques in the diagnosis of the Smith-Magenis syndrome and other small deletions are becoming an important tool in the genetic evaluation of ultrasound abnormalities.     

Persistent fifth aortic arch associated with 22q11.2 deletion syndrome.

BACKGROUND: Chromosome 22q11.2 deletion is frequently associated with conotruncal malformations and aortic arch anomalies. This study investigated the association of chromosome 22q11.2 deletion with clinical manifestations in four pediatric patients with persistent fifth aortic arch. METHODS: Four patients with persistent fifth aortic arch treated between July 1997 and June 2004 were included in this retrospective study. There were two girls and two boys, aged 2 days to 11.3 years, with persistent fifth aortic arch and cardiac conotruncal malformations. Chart recordings, plain chest films, two-dimensional and Doppler echocardiograms, cardiac catheterization with angiograms, surgical findings, and cytogenetic study were analyzed. RESULTS: Clinically, all four patients had the cardinal phenotypic features of 22q11.2 deletion syndrome, including cardiovascular malformations (conotruncal malformations and aortic arch anomalies), abnormal facies, thymic hypoplasia, canopy anomaly of the palate (high-arched palate, rather than cleft palate), and hypocalcemia (or hypoparathyroidism). All four patients were confirmed to have chromosome 22q11.2 deletion. CONCLUSION: Congenital conotruncal malformations, including tetralogy of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including a persistent fifth aortic arch or a right aortic arch, should lead to suspicion of chromosome 22q11.2 deletion when manifested together with any one of the other four cardinal phenotypic features.     

Prenatal detection of a tetralogy of Fallot with origin of the left pulmonary artery from the ascending aorta in a familial 22q11 microdeletion

Here we report a case of prenatal diagnosis of anomalous origin of the left pulmonary artery from the ascending aorta associated with a tetralogy of Fallot in a familial form of 22q11 deletion. The mother, who had a normal heart and a velo-cardio-facial syndrome, had a first child with a pulmonary atresia plus ventricular septal defect associated with a 22q11 deletion. Prenatal diagnosis during the second pregnancy identified the above-described cono-truncal anomaly and FISH study showed a recurrent 22q11 deletion. This case illustrates the intrafamilial variability of cardiac involvement in 22q11 deletion as well as the possibility of diagnosing complex cono-truncal malformations during fetal life.     

三个心脏超声切面在常见先天性心脏病产前诊断中的作用

目的 探讨三个胎儿超声心动图标准切面：四腔心切面、五腔心切面、三血管平面在发现和诊断胎儿常见先天性心脏病中的作用及对于先天性心脏病产前筛查的意义。方法 回顾2003年5月至2004年7月胎儿心脏畸形各病例的心脏超声图像，记录每一病例三个超声切面（四腔心切面、五腔心切面、三血管平面）的彩色多普勒超声图像表现，分析并总结各切面异常表现的特点。结果 （1）研究共包括胎儿心脏畸形病例26例，疾病类型包括房室间隔缺损、单纯性室间隔缺损、单心室、单心房、左心发育不良综合征、法洛四联症、右心室双出口、纠正性／完全性大动脉转位、动脉单干、主动脉瓣狭窄、肥厚性心肌病（梗阻型）、心脏肿瘤。（2）各心脏畸形病例在这三个心脏超声切面的扫查中至少有1个切面显示异常。每一类心脏畸形在这三个切面图像上均有特征性表现。（3）所有病例中二维四腔心切面（常规产科筛查切面）显示异常的比例为73％，四腔心切面未显示异常的病例包括：完全性大血管转位3例、法洛四联症1例、右心室双出口1例、动脉单干1例、主动脉骑跨伴室间隔缺损1例。（4）各标准切面获得率分别为：96．2％、88．5％、84．6％。结论 （1）四腔心切面、五腔心切面、三血管平面这三个胎儿彩色多普勒心脏超声切面探查在各类胎儿常见的先天性心脏病超声产前检查与诊断中起重要的作用。（2）与运用单个二维四腔心切面探查比较，三个切面的探查方法可提高常见先天性心脏病，尤其是胎儿心脏锥干畸形的检出率。（3）三个切面探查操作较为简便，有望成为一项胎儿先天性心脏病的筛查方法。     

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.     

The corse of pregnancy and delivery in patients with surgicaly corrected tetralogy of Fallot

Twenty-eight pregnancies in 16 patients with surgically corrected tetralogy of Fallot between 1997 and 2002 at the SBALAG "Maichin dom", Sofia, were reviewed. Most of the patients were well and asymptomatic after surgery, excluding one patient who was functional class III. The patients had a total of twenty-one successful pregnancies and deliveries. There were seven abortions (33%) and two small-for-date babies (12%). None of the infants had any cardiac anomalies. The pregnancies were relatively well tolerated and there were no life-threatening cardiac complications. For a patient with some residual abnormalities after surgical correction of tetralogy of Fallot, it is important to reassess the cardiac state before pregnancy and, if once pregnant, to anticipate the possible occurrence of complications during labor. Compared to the general obstetric population, more women in the study group underwent instrumental vaginal delivery and probably best option was elective ventouse or forceps. In conclusion despite potential difficulties and complications associated with corrected tetralogy of Fallot, careful cardiac and obstetric management resulted in good maternal and fetal outcomes.     

Ductus-dependent fetal cardiac defects contraindicate indomethacin tocolysis.

The hemodynamics of critical aortic stenosis in the fetus make it a ductus-dependent cardiac defect because the ductus arteriosus supplies blood not only to the descending aorta but also to the aortic arch and coronary vessels. In utero closure of the ductus arteriosus has been reported in association with tetralogy of Fallot, truncus arteriosus, maternal use of prostaglandin inhibitors, and as idiopathic events. This is the first report of a ductus-dependent congenital heart defect (critical aortic stenosis) where treatment with indomethacin, a prostaglandin synthetase inhibitor, precipitated premature closure of the ductus and hydrops fetalis. Review of reported cases of premature closure of the ductus show that acute, in utero closure of the ductus in a fetus with limited cardiopulmonary reserves has a worse prognosis than with previously reported cardiac anomalies. This study strongly supports published concerns of increased perinatal morbidity and mortality when fetuses are exposed to prostaglandin inhibitors in utero, and shows that ductus-dependent fetal cardiac defects are contraindications to the maternal use of prostaglandin inhibitors during pregnancy.     

Transatrial-transpulmonary repair of tetralogy of Fallot: extensive infundibular septum resection.

Twenty-seven patients with tetralogy of Fallot underwent total correction during the period from February 1988 through October 1989. Their ages ranged from 11 months to 12 years (mean 3.3 +/- 4.9 years). For 11 patients, the repair was made via the conventional transventricular approach and a partial resection of the infundibular septum. On the other 16 patients, a transatrial-transpulmonary approach was used with total resection of the anterior deviated infundibular septum, with or without a miniventriculotomy incision (1-10 mm). The exposure of the ventricular septal defect (VSD) through the right atrium, and the right ventricular outflow tract (RVOT) through the pulmonary artery in patients with tetralogy of Fallot was excellent. There were no significant differences between transatrial-transpulmonary repair and transventricular repair of the tetralogy of Fallot with respect to pulmonary artery (PA) index (273.2 +/- 36.6 versus 249.9 +/- 63.2 mm2/BSA) or the postoperative ratio of right ventricle/left ventricle (RV/LV) systolic pressure (0.55 +/- 0.16 versus 0.61 +/- 0.17). Postoperative intensive care was simple and uncomplicated, with a significantly lower catecholamine demand, less bleeding, fewer blood transfusions, and shorter stays in the cardiac Intensive Care Unit (ICU). There was no mortality in this series. This method of repair can be successfully accomplished in most patients with tetralogy of Fallot, with resultant preservation of right ventricular function (intact right ventricle).     

Prenatally evolving ectopia cordis with successful surgical treatment

Ectopia cordis (EC) is a rare malformation due to failure of maturation of the midline mesodermal components of the chest and abdomen. It can be defined as a complete or partial displacement of the heart outside the thoracic cavity. It comprises 0.1% of congenital heart diseases. Common cardiac anomalies associated with EC are ventricular septal defect, atrial septal defect, and tetralogy of Fallot. EC and additional anomalies usually lead to intrauterine death. The possibility and efficacy of surgery in a surviving neonate depends on the degree of EC, coexisting congenital heart defects and extracardiac malformations. We present a case of prenatally diagnosed isolated EC diagnosed in the first half of pregnancy. After counseling, the patient decided to continue her pregnancy which ended with a newborn baby discharged from the hospital after cardiac surgery performed just after elective cesarean section.     

Correlation between pulmonary vascular change and hemodynamics in patients with complete atrioventricular septal defect.

BACKGROUND AND PURPOSE: The study of the pulmonary vasculature in Taiwanese with atrioventricular septal defect has not been reported previously. This study investigated the correlation between pulmonary vascular change and hemodynamics in these patients. METHODS: Ten children with complete atrioventricular defect, 8 of whom had Down syndrome, underwent open lung biopsy. Their age ranged from 8 months to 6 years (mean, 2 years 7 months). Cardiac catheterization was performed and the systolic pressures of pulmonary and systemic arteries were measured immediately before cardiopulmonary bypass (CPB) and immediately after cardiac repair in 9 patients, and expressed as a ratio of pulmonary to systemic systolic pressure (Pp/Ps). RESULTS: Medial hypertrophy and intimal proliferation were prominent in 7 patients with pulmonary hypertension. The alveolar wall muscular arteries and percent arterial medial thickness increased significantly with increasing post-repair Pp/Ps, preoperative Pp/Ps, pulmonary arteriolar resistance index and pre-CPB Pp/Ps (p < 0.02). The arteries present per 100 alveoli were inversely correlated with the above mentioned hemodynamic parameters (p < 0.02). CONCLUSIONS: The results of qualitative and quantitative analyses of the pulmonary vasculature in patients with complete atrioventricular defect correlated well with pre-and postoperative pulmonary arterial pressure and can be used to predict the postoperative pulmonary arterial pressure.     

Autosomal recessive tetralogy of Fallot, unusual facies, communicating hydrocephalus, and delayed language development: a new syndrome?

We report a pattern of malformation affecting five of seven siblings born to unaffected Afghani parents who are first cousins. Their first two children died during infancy of cyanotic congenital heart defects. Two living male siblings have tetralogy of Fallot, developmental delay principally affecting language skills, and short palpebral fissures or midfacial hypoplasia. Another male has communicating hydrocephalus and hypertelorism. The striking number of siblings with tetralogy of Fallot, or another cyanotic congenital heart defect, and the parental consanguinity, suggests autosomal recessive inheritance in this family. While several other families have been identified with apparent recessive inheritance of tetralogy of Fallot, the associated malformations in our family suggest a unique, and previously unreported, malformation pattern.     

Down syndrome, achondroplasia and tetralogy of Fallot

This paper describes a female infant with achondroplasia, Down syndrome and tetralogy of Fallot. Down syndrome and achondroplasia were confirmed by karyotyping and presence of a common fibroblast growth factor receptor 3 mutation (Gly380Arg), respectively. The clinical course was complicated by pulmonary hypoplasia and subsequent intractable respiratory failure secondary to the combination of congenital conditions, which resulted in the patient's death at 5 months.     

Rate of prenatal detection of congenital right heart defects

Congenital right heart lesions (including tetralogy of Fallot, pulmonary valve stenosis, pulmonary atresia with intact ventricular septum, Ebstein's anomaly and dysplastic tricuspid valve) account for about 19% of congenital cardiac anomalies. We performed a retrospective study in order to assess the percentage of patients with significant right heart lesions (requiring therapy in the first year of life), which is detected prenatally and referred to a centre for perinatal treatment. From 1/1990 until 12/1997 congenital right heart lesions were diagnosed in 21 fetuses and 190 infants (211 patients. The majority of patients had tetralogy of Fallot (64%), less frequently we found critical pulmonary valve stenosis (9%), pulmonary atresia with intact ventricular septum (9%), tricuspid atresia (14%) and Ebstein's anomaly or dysplastic tricuspid valve (4%). Prenatally the cardiac anomaly was diagnosed in all 21 cases who were referred to our center (10%). The highest referral and detection rate was found among fetuses with Ebstein's anomaly or dysplastic tricuspid valve (5/8 patients = 63%) followed by fetuses with pulmonary atresia and intact ventricular septum (5/20 = 25%), critical pulmonary stenosis (4/18 = 22%) or tricuspid atresia (4/29 = 14%). The prenatal referral rate was disappointing in children with tetralogy of Fallot (3/136 = 2.2%). A higher prenatal detection rate of congenital right heart lesions can be achieved only by an improvement of prenatal screening including the 4-chamber view and the origin of the great arteries. A first step would be the inclusion of the fetal 4-chamber view into the routine examination during the 18th-20th week of pregnancy (stage 1 of a multistage concept of prenatal screening) and by assessment of the outflow tracts and the great arteries in pregnancies associated with risk factors or anomalies of the fetus (stage 2 and 3 of a multistage concept).     

Further delineation of interstitial chromosome 6 deletion syndrome and review of the literature

Interstitial deletions of chromosome 6q are a relatively rare finding. Deletions have ranged from the loss of a single band to larger deletions spanning multiple bands. The clinical phenotype varies, but some features commonly seen include cardiac anomalies, hypotonia, facial dysmorphism and mental retardation. To further delineate the syndrome, we report an infant with facial dysmorphism, ectrodactyly and tetralogy of Fallot owing to interstitial deletion 6q16.1-6q22.32. On array comparative genomic hybridization analysis, the deletion spanned from the 93 377 323rd base to the 127 650 582nd base on chromosome 6 [coordinates are based on Human Mar. 2006 (hg18) assembly of International Human Genome Sequencing Consortium]. A literature review identified 16 additional cases with overlapping interstitial deletions of chromosome 6q between q13 and q23.1. Genotype-phenotype correlations are considered.     

Prenatal diagnosis of de novo terminal deletion of chromosome 7q

OBJECTIVES: To present the prenatal diagnosis and perinatal findings of a de novo terminal deletion of chromosome 7q. CASE: Amniocentesis was performed at 21-weeks gestation owing to a positive result of maternal serum multiple-marker screening. The 30-year-old woman, gravida 2, para 1, had a maternal serum multiple-marker screening test at 18-weeks gestation. The risk of Down syndrome was 1/11 calculated from the gestational age, maternal age, a maternal serum alpha-fetoprotein level of 1.026 multiples of the median (MOM), and a maternal serum free beta-human chorionic gonadotrophin (hCG) level of 8.678 MoM. Cytogenetic analysis of the cultured amniotic fluid cells revealed a de novo terminal deletion of 7q, 46,XX,del(7)(q35). Ultrasonography showed intrauterine growth restriction, microcephaly, and tetralogy of Fallot. The pregnancy was terminated subsequently. Grossly, the placenta was normal. On autopsy, the proband additionally manifested a prominent forehead, hypertelorism, epicanthus, upslanting palpebral fissures, a flat and broad nasal bridge, micrognathia, large low-set ears, overriding toes, and a normal brain. Radiography demonstrated a normal spine. Fluorescence in situ hybridization analysis demonstrated a 7q terminal deletion. Genetic marker analysis showed a maternally derived terminal deletion of chromosome 7(q35-qter). CONCLUSION: Fetuses with a de novo 7q terminal deletion may be associated with a markedly elevated maternal serum hCG level and abnormal sonographic findings of intrauterine growth restriction, microcephaly, and congenital heart defects in the second trimester.     

First trimester screening for structural fetal abnormalities: Nuchal translucency sonography

Nuchal translucency refers to the normal subcutaneous space, observed on first trimester ultrasound examination, between the skin and the cervical spine in the fetus. Increased nuchal translucency is known to be associated with an increased risk of aneuploidy, particularly Down syndrome. In addition to this association with aneuploidy, multiple studies have now identified increased nuchal translucency as a nonspecific marker of a wide range of fetal structural abnormalities, to include congenital diaphragmatic hernia, cardiac defects, and various genetic syndromes. The degree of nuchal translucency is directly related to the prevalence of fetal anomalies and may have prognostic significance, especially when found in association with other anomalies. The pathophysiology of increased nuchal translucency is uncertain but may be the result of cardiac failure or alterations in lymphatic drainage. Increased nuchal translucency may identify pregnancies that require further assessment, to include additional sonographic evaluation and possible fetal echocardiography. Further evaluation is required to assess the role of nuchal translucency screening in the general population.     

Ebstein's anomaly of the tricuspid valve in association with tetralogy of fallot and absent pulmonary valve syndrome

Ebstein's anomaly and absent pulmonary valve syndrome belong to the rarest congenital heart defects. Their association has never been reported so far. We present the unusual case of a fetus at 23 weeks of gestation with Ebstein's anomaly, tetralogy of Fallot, absent pulmonary valve and agenesis of the arterial duct. The main diagnostic features were apical displacement of the septal leaflet of the tricuspid valve with an offset from the mitral valve of 8 mm, a pronounced atrialization of the right ventricle, a large malalignment ventricular septal defect with overriding aorta in combination with absence of the pulmonary valve leaflets, to and fro flow pattern over the stenotic pulmonary valve annulus, turbulent flow in the pulmonary trunk, massive dilatation of the pulmonary trunk plus the pulmonary arteries and a right aortic arch with retroesophageal course of an aberrant left subclavian artery. The arterial duct and the thymus were absent. The remaining fetal anatomy was unremarkable. Amniocentesis revealed a normal male karyotype; 22q11 microdeletion was ruled out. After being counseled on the unfavorable prognosis, the parents opted for termination of pregnancy. The prenatal cardiac findings were confirmed at autopsy; however, a severely hypoplastic thymus was found instead of the suspected aplasia.