Hypoplastic left heart syndrome: prenatal diagnosis, clinical profile, and management

We diagnosed hypoplastic left heart syndrome, generally regarded as a lethal congenital heart defect, by fetal echocardiography in 20 pregnancies in the last 5 years. The clinical profile, management, and outcome of these pregnancies were reviewed. We found a 40% association of karyotype and extracardiac malformations. Elective abortion was performed in nine pregnancies. Two of seven live-born babies had early neonatal assessment and intervention as a result of in utero diagnosis and counseling. Prolonged survival was achieved in both infants. We conclude that prenatal diagnosis of the hypoplastic left heart syndrome necessitates complete evaluation of the fetus for associated genetic and extracardiac malformations. Prenatal diagnosis of this defect provides opportunities for in depth counseling of parents and obtaining informed consent for either postnatal intervention or nonintervention before the medical and emotional complexities associated with the neonatal intensive care setting are encountered.     

Study of 156 cases of polyhydramnios and congenital malformations in a series of 118,265 consecutive births

Polyhydramnios associated with congenital anomalies was studied over nine years in 118,265 consecutive pregnancies. The prevalence of this association was 1.32% (156 cases). A case-control study allowed the examination of genetic and environmental factors for the origin of polyhydramnios associated with congenital malformations. Diagnosis of polyhydramnios associated with congenital malformations was performed prenatally in 41% of the cases; 16% of the infants were stillborn. Fifty-five percent of the cases had more than one malformation, 13.4% of them had a chromosomal aberration, and 32% had multiple malformations that do not constitute a syndrome. There was an increase of consanguinity in the parents of our patients. The incidence of polyhydramnios and congenital anomalies in first-degree relatives was 3.8%, and first-degree relatives had more malformations than the controls had (8.3% vs 3.2%). Our study demonstrated the low capacity of a general prenatal screening program because the diagnosis of malformations associated with polyhydramnios was made in only 41% of the cases and only six of 21 chromosomal abnormalities were diagnosed prenatally. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by polyhydramnios.     

Prenatal diagnosis and management of fetal cardiovascular malformations

Screening for fetal cardiovascular malformations is widely performed. Its accuracy is not yet satisfactory, but better training of ultrasonographers and extension from the four-chamber view to the study of the outflow tract are probably clues to an improvement. The main impact of prenatal diagnosis is still the termination of pregnancy for severe malformations and for those associated with chromosomal or extracardiac anomalies. There is now evidence that prenatal diagnosis improves perinatal morbidity or mortality for some malformations. New information about the molecular genetic basis of congenital heart disease will help in management and counselling.     

Prenatal diagnosis and genetic counseling in a case of spina bifida in a family with Waardenburg syndrome type I

OBJECTIVE: Waardenburg syndrome type I (WS I) is an autosomal dominant inherited disorder with an incidence of 1:45,000 in Europe. Mutations within the PAX3 gene are responsible for the clinical phenotype ranging from mild facial features to severe malformations detectable in prenatal diagnosis. METHODS: Here, we report a four-generation family with several affected members showing various symptoms of WS I. We diagnosed the syndrome first in a pregnant young woman; she was referred because of a spina bifida in prenatal diagnosis. We performed clinical genetic investigations and molecular genetic analysis in all available family members. RESULTS: The phenotype displays a wide intra-familial clinical variability of pigmentary disturbances, facial anomalies and developmental defects. Molecular studies identified a novel splice site mutation within the PAX3 gene in intron 5 in all affected family members, but in none of the unaffected relatives. CONCLUSIONS: This case demonstrates the prenatal diagnosis of spina bifida in a fetus which leads to the initial diagnosis of WS I. Further studies could identify a private splice site mutation within the PAX3 gene responsible for the phenotype in this family.     

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.     

Fetal cardiac anomalies and genetic syndromes

Cardiac anomalies may occur in isolation or can be part of a genetic syndrome. In this article, we describe some of the genetic syndromes commonly associated with cardiac anomalies where there are other sonographic features that may aid accurate prenatal diagnosis.     

Syndromes and disorders associated with omphalocele (II): OEIS complex and Pentalogy of Cantrell

Omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is characterized by a combination of omphalocele, exstrophy of the bladder, an imperforate anus, and spinal defects. Pentalogy of Cantrell is characterized by a combination of a midline supraumbilical abdominal wall defect, a defect of the lower sternum, a defect of the diaphragmatic pericardium, a deficiency of the anterior diaphragm, and congenital cardiac anomalies. This article provides a comprehensive review of OEIS complex and pentalogy of Cantrell, including the pathogenesis, prenatal diagnosis, differential diagnosis, and associated malformations. Omphalocele is an important sonographic marker for OEIS complex and pentalogy of Cantrell. Prenatal detection of an abdominal wall defect associated with multiple midline defects should alert one to the possibility of OEIS complex and pentalogy of Cantrell and prompt the genetic investigation and counseling of the disorders.     

Prenatal diagnosis of hemifacial microsomia by magnetic resonance imaging

We present a case of hemifacial microsomia, first detected by prenatal sonography and confirmed by ultrafast magnetic resonance (MR) imaging. A 26-year-old patient was referred to our hospital at 20 weeks of gestation because of unilateral right-sided ventriculomegaly and of a possible ventriculoseptal defect (VSD). Our sonographic examination suggested a right orbital hypoplasia and a hemiatrophy of the nose. The ultrafast T2-weighted single-shot fast-spin echo MR imaging, demonstrated a right ear hypoplasia (microtia), a right orbital hypoplasia, and a right renal hypoplasia. Epibulbar dermoid or conjunctival lipodermoid were not recognized. The fetus was prenatally diagnosed as hemifacial microsomia. Termination of pregnancy was performed at 21 weeks gestation, and a male baby weighing 342g was stillborn. The baby showed facial asymmetry, including hemiatrophy of the right nose, and right ear hypoplasia. Autopsy revealed a 2mm area of VSD, agenesis of the right kidney and ureter, pancreatic and renal aberration into right adrenal gland, thymus hypoplasia and an unfixed ascending colon without intestinal malrotation. To the best of our knowledge, this is the first report of prenatal diagnosis for hemifacial microsomia using fetal MR imaging. In our case, fetal MR imaging has evolved into a powerful diagnostic tool, for the accurate prenatal diagnosis.     

Successful pregnancy in a Noonan syndrome patient after 3 unsuccessful pregnancies from severe fetal hydrops: a case report

BACKGROUND: Noonan syndrome is a very rare disorder; its prevalence is 1/1,000-2,500 births. The special facial features, short stature, eventual cardiac anomalies and familiar history are the most important characteristics of the diagnosis. CASE: A Noonan syndrome patient delivered a healthy infant after a complicated delivery. The delivery followed 3 unsuccessful pregnancies. The previous pregnancies were terminated before the 24th gestational week because of general fetal hydrops as well as other malformations. CONCLUSION: In the prenatal care of a patient with Noonan syndrome the genetic and obstetric aspects are equally important. In establishing the diagnosis, ultrasonography is of utmost importance. As in our case, complications after cesarean section highlight the higher risk of delivery in women with Noonan syndrome.     

Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts

In utero diagnosis of de novo distal 11q deletion associated with renal and orofacial malformations has not been previously described. We present a 35-year-old pregnant woman with prenatal sonographic findings of a unilateral duplex renal system, pyelectasis and orofacial clefts at 20 weeks' gestation. Both genetic amniocentesis and postnatal cytogenetic analysis revealed de novo 46,XX,del(11)(q23). After birth, the fetus manifested a dysmorphic phenotype correlated with del(11q) syndrome. Genetic marker analysis showed a paternally derived distal deletion of chromosome 11q and a breakpoint centromeric to D11S1341. The present case represents the earliest prenatal diagnosis of a duplex renal system, pyelectasis and an additional feature of orofacial clefts associated with distal 11q deletion. Prenatal sonographic detection of a duplex renal system, pyelectasis and orofacial clefts should warrant a careful assessment of fetal anatomy and prompt cytogenetic analysis looking for chromosomal aberrations.     

Insight into the Genetic Relevance of Congenital Heart Defects

Congenital heart disease is the most common type of birth defect in the newborn??occurring in 1?% of neonates. In addition, cardiac defects account for nearly half of the neonatal deaths resulting from congenital malformations. Due to recent advances in spatial resolution of ultrasound machines and improvements in sonographic techniques, the clinician is increasingly able to detect cardiac anomalies in utero. At the same time, advances in cardiovascular surgery have improved the overall survival of the affected neonates. Due to the combination of advances in prenatal diagnosis and postnatal intervention, parents with fetuses affected by congenital cardiac defects have become the largest group who seek prenatal counseling on the risks of associated anomalies, risks for subsequent pregnancies, and the risks to the offspring of a successfully treated patient. Although most congenital heart defects are not familiarly clustered, genetic factors are still involved in most cases. In this review, we summarize recent evidence of chromosomal and genetic defects associated with congenital heart diseases to provide the optimal counseling and management for the parents with affected neonates.     

A newborn infant with left diaphragm agenesis, radial aplasia and preauricular appendices

We report the case of a baby girl born to consanguineous parents who died 36 hours after birth. She had multiple preauricular appendices, right radial aplasia, triphalangeal thumb and several other anomalies. Differential diagnosis included Fryns syndrome, Pallister-Killian syndrome, and hemifacial microsomia. However, since our patient had congenital diaphragmatic hernia, a rare finding in hemifacial microsomia we suggest that she had a variant form of hemifacial microsomia or an undescribed new syndrome.     

Sonographic evaluation of fetal clefts of the lip, alveolus and palate

Clefts of the lip, alveolus and palate are among the most common congenital malformations. Due to their frequent combination with other structural anomalies, chromosomal defects and genetic syndromes, the prenatal diagnosis of clefts plays an important role. Furthermore, the prenatal detection of clefts enhances the parents' psychological preparation and enables the planning of postnatal management. This article reviews the occurrence, appearance and pathophysiology of these malformations as well as the different sonographic techniques used to diagnose clefts and their extent. Previously reported 2D- and 3D-techniques as well as our own recent diagnostic approach focussing on the diagnosis of isolated cleft palate are described.     

Prenatal isolated mild ventriculomegaly: outcome in 167 cases

OBJECTIVE: To define the contribution of prenatal investigation and evaluate the prognosis of isolated mild ventriculomegaly (IMV). DESIGN: Retrospective study. SETTING: University hospital between January 1992 and December 2002. POPULATION: One hundred and sixty-seven cases of prenatal unilateral or bilateral IMV without any associated anomaly at the time of initial diagnosis. METHODS: Complementary investigations were performed: amniocentesis with karyotyping, screening for viruses and acetylcholinesterase electrophoresis, magnetic resonance imaging (MRI), and ultrasonography every 3-4 weeks. MAIN OUTCOME MEASURES: Results of prenatal investigations, pregnancy outcome, and postnatal psychomotor development. RESULTS: IMV was diagnosed around 26.5 weeks. Amniocentesis revealed four chromosomal anomalies and two cytomegalovirus infections. MRI diagnosed brain-associated anomalies in 15 cases and ultrasonographic monitoring highlighted malformations not initially diagnosed in 28 cases. Termination of pregnancy (TOP) was considered in 21 pregnancies (12.6%). Indications were aneuploidy, fetal infectious disease or associated malformations. In women for whom a TOP was considered, consanguinity, fetus of female sex and frontal horn enlargement were statistically more frequent, ventriculomegaly was more often bilateral and asymmetrical, atrial width, and the rate of progressive ventricular enlargement were significantly higher. One hundred and one children with prenatal IMV were assessed between 19 and 127 months (mean age 54.68 +/- 2.87 months). Twelve children had neurological disease or psychomotor delay and 89 children had a normal psychomotor development. Poor neurological outcome was more often associated with atrial width greater than or equal to 12 mm, asymmetrical bilateral enlargement, and progression of the ventriculomegaly. CONCLUSION: The detection of IMV raises the question of the child's psychomotor development and justifies meticulous prenatal investigation. In addition to associated anomalies, three criteria are often associated with an unfavourable outcome: atrial width greater than 12 mm, progression of the enlargement, and asymmetrical and bilateral ventriculomegaly.     

Application of the three-dimensional maximum mode in prenatal diagnosis of Apert syndrome

Apert syndrome is a rare disorder characterized by coronal craniosynostosis, syndactyly, brachycephaly, midfacial hypoplasia, and central nervous system anomalies, among other malformations. We present a case of Apert syndrome examined at 22 + 0 weeks' gestation. Three-dimensional maximum mode was decisive for the correct prenatal diagnosis by demonstrating the cranial deformities.     

3-D ultrasound in prenatal diagnosis

2-D ultrasonography has evolved into an excellent technique in prenatal diagnosis during the past 40 years. The fact remains, however, that 2-D ultrasonography is marked by a lack of ability to provide more than a 2-D demonstration of a 3-D fetus. Although many fetal anomalies are detectable by conventional 2-D ultrasound, it is impossible to demonstrate a defect in the third dimension. 3-D sonography not only offers the third plane, but it also provides the examiner with different viewing modes: the multiplanar, the surface and the transparent demonstration of the fetus. The different viewing modes not only improve the accuracy in detecting fetal malformations, but also serve to demonstrate the normal anatomy of the unborn more conclusively to the parents.     

Prenatal ultrasonographic recognition of Goldenhar's syndrome

Goldenhar's syndrome is a series of malformations involving the face, either unilaterally or bilaterally. Other organs, such as the lungs, kidneys, spine, and heart, can also be involved. We report the prenatal ultrasonographic findings with regard to a fetus with multiple anomalies where Goldenhar's syndrome was not diagnosed until after birth. The importance of finding patterns of malformations is stressed to optimize the postnatal care for infants with multiple congenital abnormalities.     

Concordant familial segregation of atrial septal defect and Axenfeld-Rieger anomaly in father and son

The association of congenital heart defect and ocular malformations is involved in several genetic syndromes, metabolic diseases and environmental entities. We report here on father and son, both presenting with the combination of atrial septal defect and congenital ocular anomalies in Axenfeld-Rieger anomaly. The son had anterior iridotrabecular dysgenesis and posterior embryotoxon bilaterally, corneal leucoma and marked iridial vascularization at right. The father had bilateral anterior iridotrabecular dysgenesis, posterior embryotoxon and nystagmus, and corneal leucoma at left. No additional malformations were noted in these patients. The Axenfeld-Rieger syndrome seems to be a spectrum of developmental disorders. The present report confirms the existence of a specific Axenfeld-Rieger phenotype associated with congenital heart defect. Atrial septal defect is the anatomic type of congenital heart defect linked to this condition.     

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.     

Prenatal diagnosis of Aicardi-Goutières syndrome

OBJECTIVES: Aicardi-Goutières syndrome is an autosomal recessive neurodegenerative disorder inducing cerebral atrophy, intracerebral calcification and developmental arrest. Diagnosis requires the presence of progressive encephalopathy with clinical onset shortly after birth, typical neuroimaging features associated with a raised blood and cerebrospinal fluid interferon-alpha level.A case of prenatal diagnosis of Aicardi-Goutières syndrome is reported. METHODS: An MRI performed at 26 gestational weeks showed bilateral calcifications and white matter abnormalities, cerebral anomalies typically described in this disease. The fetal blood analysis revealed an increase in interferon-alpha. RESULTS: Therefore, the prenatal diagnosis of Aicardi-Goutières syndrome in this fetus was based on the following facts: the familial background with the affected first child and consanguineous parents, a normal pregnancy and normal fetal growth, cerebral anomalies diagnosed on prenatal ultrasound and cerebral MRI, raised interferon-alpha in the fetal serum and no evidence of any infectious etiology. The autopsy performed postdelivery at 28 1/2 weeks' gestation confirmed the diagnosis of Aicardi-Goutières syndrome. CONCLUSION: To the best of our knowledge, this is the first prenatal diagnosis of this syndrome. Such a diagnosis may prove useful for families at risk as long as genetic screening is not available.